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jacky
01-09-2005, 05:01 PM
long acting opiate agonist and anti diarrheal OTC drug called loperamide is structurally related to methadone. the drug has aboiut a 72 hour stay in the body, the merabolites of loperamide actually build to greater amounts on the second day after dosing. with 10 opiate experienced people taking the drug only 1 described any sort of euphoria from the drug. this interests me as this 1 in 10 number is described by some as a general consistant percentage of people who experience euphoria from other opiates. I talked to other opiophiles that have used loperamide to kick other opiate substances. I have used loperamide in conjunction with other opiates in an attempt to percieve any potentiation of those drugs. this loperamide is the only OTC opioid regularly offered without a prescription in the united states besides the irregularly supplied OTC codeine cough syrup. I have gone through some severe detox's unaware that this drug even existed. I notice a surge of energy when I consume loperamide initially, and have consumed it at work when starting to suffer anxiety/cold chills from cutting other opiates dosages. Its amazing to me that in a country where people insidiously avoid discussing opiate pharmacology that this drug is just hanging out, nowhere on the package does the product warn opiate abstainers that the product could encourage relapse etc. why cant he facts be presented first hand? probably because telling the truth would put the power in the hands of the masses. finally I wonder just what potentially more potent opioids may be synthesized from loperamide? I asked this question in the hive but the post went unanswered, and now the hive doesnt even exist. lopermide, the long acting, mild and legal OTC opiate goes basically unabused and perhaps underapppreciated. the antidiarrheal tag perhaps is associated with the mundane.

Paregoric Kid
01-09-2005, 09:36 PM
actually loperamide is related to meperidine not methadone and it might not be a smart idea to mess around with loperamide in the lab unless you know EXACTLY what you are doing because if you don't know EXACTLY what you are doing the risks of contaminating a batch with MPTP is too great. MPTP is related to loperamide and meperidine and chemically induces parkinsonism/parkinson's disease.

bi11i
01-10-2005, 12:00 AM
i survived on loperamide for at least a couple of weeks from my attempt at sobriety from bup. did wonders to my guts and not much else...

bi11i
01-12-2005, 08:48 PM
i take that back. it did help. it helped in a bigger way than I'd thought. In fact, it was that last little kick that if I could've let go, I might've actually kicked without too much of a problem. it did totally fuck up my system though; no questions there.

Nuke
01-16-2005, 05:12 AM
loperamide is a potent opioid agonist, allthought because it's Too soluble in water it dosent pass the blood/brain barrier and is only of use as a cure for diarhhea. If given intrathecally or intracranially it dosent have to pass the barrier and therefore works as a potent opioid agonist.

Paregoric Kid
01-16-2005, 09:07 AM
no it is NOT water soluble
if you could attach microscopic pieces of plastic to it, it would cross the BBB, it would be loperamide polystirex, just like dextromethorphan is sold as dxm polystirex in delsym syrup.
it attaches to the opiate receptors in your GI tract which if you use opiates orally will especially be used to opiates, so this would solve the shits problem because, from your GI tracts perspective your basically still on dope lol

Nuke
01-16-2005, 08:54 PM
yah sorry I know its very sparingly soluble in water. Im not really sure about the polistirex though. I dont see how that could make a difference. I have read though that taking a P-Glycoprotein inhibitor like say quinidine does assist in giving loperamide CNS activity because loperamide is a substrate of p-glycoprotien. theres not a lot of information regarding this though.

Paregoric Kid
01-18-2005, 11:35 AM
Pharm Res 1997 Mar;14(3):325-328 Delivery of loperamide across the blood-brain barrier with polysorbate 80-coated polybutylcyanoacrylate nanoparticles.

Alyautdin RN, Petrov VE, Langer K, Berthold A, Kharkevich DA, Kreuter J

Department of Pharmacology, Sechenov Medical Academy, Moscow, Russia.

PURPOSE: The possibility of using polysorbate 80-coated nanoparticles for the delivery of the water insoluble opioid agonist loperamide across the blood-brain barrier was investigated. The analgesic effect after i.v. injection of the preparations was used to indicate drug transport through this barrier. METHODS: Loperamide was incorporated into PBCA nanoparticles. Drug-containing nanoparticles were coated with polysorbate 80 and injected intravenously into mice. Analgesia was then measured by the tail-flick test. RESULTS: Intravenous
injection of the particulate formulation resulted in a long and significant analgesic effect. A polysorbate 80 loperamide solution induced a much less pronounced and very short analgesia. Uncoated nanoparticles loaded with loperamide were unable to produce analgesia. CONCLUSIONS: Polysorbate 80-coated PBCA
nanoparti cles loaded with loperamide enabled the transport of loperamide to the brain.

PMID: 9098875, UI: 97253432

Life Sci 1983;33 Suppl 1:315-318 Loperamide: evidence of interaction with mu and delta opioid receptors.

Giagnoni G, Casiraghi L, Senini R, Revel L, Parolaro D, Sala M, Gori E

Loperamide was tested on electrically-evoked contractions using a series of "in vitro" isolated preparations, in comparison with morphine, met-enkephalin, beta-endorphin, ethylketocyclazocine used as representative agonists of mu, delta, epsilon, kappa receptors respectively. The IC50 of loperamide on myenteric
plexus longitudinal muscle of guinea pig ileum was found to be 1.90 X 10(-7)M and equal to that of morphine. The IC50 on mouse vas deferens was found to be 13.02 X 10(-7)M. In this tissue, loperamide resulted as active as morphine, but 54 times less active than met-enkephalin (IC50 0.24 X 10(-7)M). On the rat vas
deferens where, as expected, beta-endorphin was strongly active (IC50 1.38 X 10(-7)M), morphine exerted a stimulatory action within the range 10(-5)M-10(-4)M and loperamide was only poorly depressive. The Ke value of naloxone, a specific mu receptor antagonist, against loperamide in the guinea pig ileum was 3.83 nM, and in the mouse vas deferens was 82.87 nM indicating that
loperamide in the guinea pig ileum acts on mu receptors while in the mouse vas deferens on another opiate receptor.

PMID: 6319884, UI: 84116593

cate
02-01-2005, 03:50 PM
"CONCLUSIONS: Polysorbate 80-coated PBCA
nanoparticles loaded with loperamide enabled the transport of loperamide to the brain."


Gee...All we need to do now is get some of those particles.


Why do people seem to feel the need to do things the hard way? Anti-D. medications are just not a realistic option for producing any good feelings in the vast majority of people. Of course, that is why it does not have a great addiction potential and is available OTC.


*Just because you CAN abuse something does not mean you should try to.*

Nuke
02-02-2005, 02:33 AM
why abuse an Anti-D med.....hmm well it is a potent opioid agonist just like heroin , so why the fuck not? I dont think you understand, Yes, it constipates people but so does heroin and morphine, the problem is getting the goodness into your brain and not just in your stomach. BTW paregoric those papers were really interesting.

bi11i
02-02-2005, 10:18 AM
i think what started the loperamide discussion was using it as a way to NOT get sick during rougher times.

i could never take enough of that shit to 'feel good' on it, but it did keep me sleeping through the tougher nights....

jacky
02-02-2005, 02:17 PM
people need to reconsider what we are calling the BRAIN. BRAIN tissue is even found in the stomach, and other parts of the body. even a little relief, like the support that clonidine can provide, or the relaxant qualities of some muscle relexants can be the bridge to detox. I detoxed off of heroin, outpatient, using clonipin, muscle relaxants and tegretol. this mix was consumed while I was around dope for two weeks. besides some ketamine I didnt relapse. the ketamine helped withdrawl actually. WHAT i HOPE TO POINT OUT TO PEOPLE is that the world of opiate pharmacology is much bigger than most consider. there are alternative paths to recoverythat go unchallenged. the box of loperamide doesnt even say its an opiate, yet in a test 1 out of 10 people said that it was moderately enjoyable. this is a "common" number maybe considering opiates, in that some studies report that 10% of the population only feels euphoria from opiates anyway. Loperamide may not be a valuable street drug, and I dont care if it has that potential. the potential of loperamide is that it can cover some withdrawls concerning opiate detox in some people.

lifelong pain
02-22-2005, 12:12 AM
Loperamide in doses from 72-200mg WILL surpress opiate withdrawls, will relieve pain and will cause major constipation. So, I will eat nuts (oils) and consume high fiber foods. It is interesting how little is written about the analgesic effects of this drug. My Doctor prescribes Tylenol with Codeine #4's and believe what you want, but the Loperamide helps my Mysfacial pain much better than Tylenol #4. Also, I've stopped taking Loperamide and have experienced some bad withdrawls. The problem is the stuff is expensive. You can get it in bottles of 98 or 48 tablets.

Paregoric Kid
03-13-2005, 12:31 PM
Intranasal delivery: An approach to bypass the BBB

Talegaonkar S, Mishra PR
Department of Pharmaceutics, Jamia Hamdard, New Delhi -110062, India

Correspondence Address:
Department of Pharmaceutics, Jamia Hamdard, New Delhi -110062, India
stalegaonkar@hotmail.com (stalegaonkar@hotmail.com)

Abstract

The blood brain barrier (BBB) represents one of the strictest barriers of in vivo therapeutic drug delivery. The barrier is defined by restricted exchange of hydrophilic compounds, small proteins and charged molecules between the plasma and central nervous system (CNS). For decades, the BBB has prevented the use of many therapeutic agents for treating Alzheimer's disease, stroke, brain tumor, head injury, spinal cord injury, depression, anxiety and other CNS disorders. Different attempts were made to deliver the drug across the BBB such as modification of therapeutic agents, altering the barrier integrity, carrier-mediated transport, invasive techniques, etc. However, opening the barrier by such means allows entry of toxins and undesirable molecules to the CNS, resulting in potentially significant damage. An attempt to overcome the barrier in vivo has focused on bypassing the BBB by using a novel, practical, simple and non-invasive approach i.e. intranasal delivery. This method works because of the unique connection which the olfactory and trigeminal nerves (involved in sensing odors and chemicals) provide between the brain and external environments. The olfactory epithelium acting as a gateway for substances entering the CNS and peripheral circulation is well known. Also, it is common knowledge that viral infections such as common cold, smallpox, measles, and chicken pox take place through the nasopharynx. The neural connections between the nasal mucosa and the brain provide a unique pathway for the non-invasive delivery of therapeutic agents to the CNS. This pathway also allows drugs which do not cross the BBB to enter the CNS and it eliminates the need for systemic delivery and thereby reducing unwanted systemic side effects. Intranasal delivery does not require any modification of therapeutic agents and does not require that drugs be coupled with any carrier. A wide variety of therapeutic agents, including both small molecules and macromolecules can be rapidly delivered to the CNS using this method. The present review discusses the various applications, advantages and limitations of this novel approach.

keyword: Intranasal delivery: An approach to bypass the blood brain barrier
author: Talegaonkar S, Mishra PR
http://www.ijp-online.com/search.asp (http://www.ijp-online.com/search.asp)

Paregoric Kid
03-13-2005, 12:41 PM
(iii)Bypassing the BBB: The third and the emerging approach is to bypass the BBB by intranasal delivery, which provides a practical, non-invasive, rapid and simple method to deliver the therapeutic agents to the CNS. This method works because of the unique connection between the nose and the brain that has evolved to sense odors and other chemical stimuli. This method is the thrust of this article.
Recently, Illum[7] has thoroughly reviewed the possibilities, problems, and solutions of nasal drug delivery. She has reported that it is feasible to deliver challenging drugs efficiently such as small polar molecules, peptides and proteins and even the large proteins and polysaccharides like vaccines or DNA plasmids exploited for DNA vaccines. On the basis of clinical trials (Phase I and II) it is reported that the intranasal route is feasible for the transport of the drug to the CNS.
Intranasal delivery does not require any modification of the therapeutic agents and does not require that drugs be coupled with any carrier like in case of drug delivery across the BBB. A wide variety of therapeutic agents, including both small molecules and macromolecules can be successfully delivered, including to the CNS, using this intranasal method [Table - 1].

Advantages
The advantages of intranasal delivery are considerable. This method is:
(1) Non-invasive, rapid and comfortable
(2) Bypasses the BBB and targets the CNS, reducing systemic exposure and thus systemic side effects
(3) Does not require any modification of the therapeutic agent being delivered
(4) Works for a wide range of drugs. It facilitates the treatment of many neurologic and psychiatric disorders
(5) Rich vasculature and highly permeable structure of the nasal mucosa greatly enhance drug absorption
(6) Problem of degradation of peptide drugs is minimized up to a certain extent
(7) Easy accessibility to blood capillaries
(8) Avoids destruction in the gastrointestinal tract, hepatic “first pass” elimination and gut wall metabolism, allowing increased, reliable bioavailability.

Limitations
(1) Concentration achievable in different regions of the brain and spinal cord, varies with each agent
(2) Delivery is expected to decrease with increasing molecular weight of drug
(3) Some therapeutic agents may be susceptible to partial degradation in the nasal mucosa or may cause irritation to the mucosa
(4) Nasal congestion due to cold or allergies may interfere with this method of delivery
(5) Frequent use of this route results in mucosal damage (e.g. infection, anosmia).

How does it work?
To understand the mechanism, pathways, distribution and absorption of therapeutic agents administered to the CNS by the intranasal route, a brief description of the nasal physiology is considered necessary.

Nasal physiology
The nose is divided into two nasal cavities via the septum. The volume of each cavity is approximately 7.5 mL and has a surface area around 75 cm.[2],[8],[9] There are three different functional regions in the nose-vestibular, respiratory, and olfactory. Of these, the respiratory region is the most important for systemic drug delivery.[9] The respiratory epithelium consists of basal, mucus-containing goblet, ciliated columnar and non-columnar cell types.[9],[10] The Celia move in a wavelike fashion to transport particles from the pharynx area for ingestion.[9],[11] Additionally, the cells in this region are covered by 300 microvilli, providing a large surface area for absorption.[9] Below the epithelium is lamina propria. This is the region where blood vessels, nerves, serous glands, and mucus secretory glands may be found.[10] The lamina propria also houses a dense network of capillaries, many of which are very permeable for drug absorption.[8],[12]
The nasal epithelium is covered by a mucus layer that is renewed every 10 to 15 min.[12] The pH of mucosal secretion ranges from 5.5 to 6.5 in adults and from 5.0 to 6.5 in children.[13] The mucus layer entraps particles, which are then cleared from the nasal cavity by the cilia. The rate of mucus flow through the nose is approximately 5 to 6 mm/min resulting in particle clearance within the nose every 20 min.[8],[14]
The nasal cavity also houses numerous enzymes.[14],[15],[16] In humans, cytochrome P450 enzyme isoforms that have been identified are CYP1A, CYP2A and CYP2E.[17] Other enzymes detected in the human nose include carboxylesterases and glutathione S-transferases.[18],[19],[20]
In addition to its function as a passageway for respiration, the nasal cavity also has a key role in the sense of smell. The olfactory nerves, which originate as specialized olfactory nerve endings (chemoreceptors) in the mucous membrane of the roof of the nasal cavity above the superior nasal conchae, are the sensory nerves of smell. On each side of the septum nerve fibers pass through the cribriform plate of the ethmoid bone of the olfactory bulb where interconnections and synapses occur. From the bulb, a bunch of nerve fibers pass through the olfactory tract and reach the olfactory area in the temporal lobe of the cerebral cortex in each hemisphere, where the impulses are interpreted and odor is perceived. Another set of nerves emanating from the nasal cavity is the maxillary branch of the trigeminal nerves, which are general sensory nerves[21] [Figure:2].

Mechanisms
Two mechanisms are involved in the nasal delivery, a fast rate that depends on lipophilicity, and a slower rate that depends on molecular weight. McMartin et al studied[22] the transport of SS-6 (an octapeptide) and horseradish peroxidase through a rat's nasal cavity. Their absorption studies are consistent with the non-specific diffusion of the penetrant molecules through aqueous channels located between the nasal mucosal cells, which impose a size restriction on nasal permeability. The data indicate that good bioavailabilities can be achieved for molecules up to 1000 Da (without enhancers) and good availability can be extended to at least 6000 Da with enhancers.
The transport mechanisms of different substances like insulin, mannitol or propranolol across the nasal mucosal tissue were studied by Wheatly et al.[23] The transport of these substances occurs by a passive transport mechanism. The addition of deoxycholate (0.1%) reversibly increased the transepithelia conductance across the nasal membrane and enhanced the transport of mannitol and insulin. The transport of tyrosine and phenylalanine across rat mucosa was also studied by using an in-situ perfusion technique.[24] It was found that both amino acids were absorbed by an active saturable transport process, which appeared to be Na+ dependent, and transport may have required metabolic energy as a driving force.
Water-soluble substances such as sodium cromoglycate are absorbed well and nasal absorption probably depends on aqueous channel diffusion (pores).[25] The molecular size of the compound will be a determinant in the rate of absorption in such a channel.

Pathways
The olfactory epithelium is a gateway for substances entering the CNS and the peripheral circulation. The neural connections between the nasal mucosa and the brain provide a unique pathway for the non-invasive delivery of therapeutic agents to the CNS.[9],[11],[26] The olfactory neural pathway provides both an intraneuronal and extraneuronal pathway into the brain.[27],[28],[29] The intraneuronal pathway involves axonal transport and requires hours to days for drugs to reach different brain regions. While the extraneuronal pathway probably relies on bulk flow transport through perineural channels, which deliver drugs directly to the brain parenchymal tissue and/or CSF. The extraneuronal pathway allows therapeutic agents to reach the CNS within minutes.[30],[31],[32],[33] Intranasal delivery of agents to the CSF is not surprising as CSF normally drains along the olfactory axon bundles as they traverse the cribriform plate of the skull and approach the olfactory submucosa in the roof of the nasal cavity, where the CSF is then diverted into the nasal lymphatics.[34],[35],[36] Thorne et al[26] have reported that the trigeminal neural pathway may also be involved in rapidly delivering protein therapeutic agents, such as insulin-like growth factor-1 to the brain and spinal cord following intranasal administration. The transport of drugs across the nasal membrane and into the bloodstream may involve either passive diffusion of drug molecules through the pores in the nasal mucosa or some form of non-passive transport.[37] The potential pathways involved in the nasal absorption of drugs are shown in [Figure:2].


» Drug distribution

Drug distribution in the nasal cavity is an important factor that affects the efficiency of nasal absorption. The mode of drug administration may affect this distribution, which in turn can help determine the extent of absorption of a drug. Nasal deposition of particles is related to the individual's nasal resistance to airflow.[38] With nasal breathing, nearly all the particles having an aerodynamic size of 10-20 mm are deposited on the nasal mucosa.[39] The deposition of particles in the respiratory tract is a function of particle size and respiratory patterns. The density, shape, and hygroscopicity of particles, and the pathological conditions in the nasal passage will influence the deposition of the particle, whereas the particle-size distribution will determine the site of deposition and affect the subsequent biological response in animals and humans.[40] Furthermore, improvement of the delivery system and drug formulation is necessary to achieve a better clinical effect and easier handling by patients.

Three mechanisms are usually considered in assessing particle deposition in the respiratory tract, i.e., inertia, sedimentation and diffusion, the first being the dominant mechanism in nasal deposition.[41] Any particle with an aerodynamic diameter of 50 mm or greater does not enter the nasal passage. It was demonstrated that 60% of aerosolized particles of 2-20 mm are deposited in the anterior regions of the nostrils, 2-3 mm from the external nares.[42] The site of drug deposition within the nasal cavity depends on the type of delivery system and the technique used in application.[43]


» Drug absorption

The first step in the absorption of drugs from the nasal cavity is passage through the mucus.[44] Small, uncharged particles easily pass through this layer. However, larger or charged particles may find it more difficult to cross. Mucin, the principal protein in the mucus, has the potential to bind solutes, hindering diffusion. Additionally, structural changes in the mucus layer are possible as a result of environmental changes (i.e., pH and temperature).[44] After a drug's passage through the mucus, there are several mechanisms for absorption through the mucosa.[45] These include transcellular or simple diffusion across the membrane, paracellular transport via movement between cells, and transcytosis by vesicle carriers.[22] Obstacles to drug absorption are, potential metabolism before reaching the systemic circulation and limited residence time in the cavity.
Nasal absorption is affected by molecular weight, size, formulation pH, pKa of molecule, and delivery volume among other formulation characteristics. Molecular weight still presents the best correlation to absorption.[46],[47] The apparent cut-off point for molecular weight is approximately 1,000 daltons, with molecules less than 1,000 having better absorption.[23]
Shape is also important. Linear molecules have lesser absorption than cyclic-shaped molecules.[22] Additionally, particles should be larger than 10 mm, otherwise the drug may be deposited in the lungs.[48]
Hydrophilicity has been found to decrease a drug's bioavailability.[49] pH is also an important formulation factor for drug absorption. Both the pH of the nasal cavity and pKa of a particular drug need to be considered to optimize systemic absorption. Nasal irritation is minimized when products are delivered with a pH range of 4.5 to 6.5.[50]
Volume and concentration are also important considerations. The delivery volume is limited by the size of the nasal cavity. An upper limit of 25 mg/dose and a volume of 25 to 150 mL/nostril have been suggested.[50]


» Applications


Delivery of protein therapeutic agents /Macromolecules to CNS
In the age of advanced peptide, protein, and vaccine research, nasal administration of such compounds provides an attractive delivery route. In case of oral administration, the bioavailability of protein molecules tends to be relatively low due to their large molecular size and rapid enzymatic degradation.[51] Because of their physicochemical instability and susceptibility to hepato-gastrointestinal “first pass” elimination, peptide/protein drugs are generally administered parenterally. It is on this background that intranasal administration seems a promising option. Most nasal formulations of peptide/protein drugs have been made up in simple aqueous or saline solutions with preservatives. Recently, more R&D work has been directed towards the development of nasal drug delivery systems for peptide/proteins. Currently, in the United States only four intranasal pharmaceutical products for systemic delivery have been marketed i.e. desmopressin (DDAVP), lypressin (Diapid), oxytocin (Syntocinon), and nafarelin acetate (Synarel).
Delivery of protein therapeutic agents to the CNS clearly involves extraneuronal transport as it occurs within minutes rather than hours. A number of protein therapeutic agents have been successfully delivered to the CNS using intranasal delivery in a variety of species. Neurotrophic factors such as NGF,[30],[31],[32] IGF-I,[33] FGF[52] and ADNF12 have been intranasally delivered to the CNS in rodents.[53] Studies in humans, with proteins such as AVP,[54] CCK analog,[55] MSH/ACTH[56],[57] and insulin[58],[59] have revealed that they are delivered directly to the brain from the nasal cavity. Hussain[60] recently reviewed animal models to study nasal absorption and the effect of physico-chemical and biopharmaceutical properties of drugs on the rate and extent of absorption. The review also discusses factors affecting peptide absorption and methods to improve the nasal bioavailability of peptides.
The bioavailability of protein molecules tends to be relatively low due primarily to their large molecular size and rapid enzyme degradation. As the number of amino acids increases beyond about 20, bioavailability becomes very low.[51] To overcome these issues, much research has been conducted in the areas of absorption enhancers and bioadhesive agents. Absorption enhancers are used to increase the bioavailability. They are basically surfactants, glycosides, cyclodextrin and glycols. They improve absorption through many different mechanisms, such as increasing membrane fluidity, increasing nasal bloodflow, decreasing mucus viscosity, and enzyme inhibition.[46] The classic example of a polypeptide compound with low nasal bioavailability is calcitonin. Its molecular weight is approximately 3,500 daltons and contains 32 amino acids in length. When calcitonin was given intranasally to rats and rabbits using a number of different cyclodextrins, its absorption as measured by a decrease in serum calcium concentration, was significant in comparison to the formulation without additive.[61]
Another technique aimed to increase nasal absorption is the utilization of bioadhesive agents. These compounds promote binding of drugs to biological material in the nasal cavity, thereby extending their residence time and allowing increased absorption. Common bioadhesive materials are carbopol, cellulose agents, starch, dextran, and chitosan.[62],[63],[64],[65],[66],[67]
Liu et al[68],[69] have demonstrated the therapeutic benefit of intranasal delivery of proteins in stroke studies. They have shown that intranasal IGF-I reduces infarct volume and improves neurologic function in rats with middle cerebral artery occlusion (MCAO). A preliminary report indicates that intranasal treatment is effective even when delayed for 4 h after the onset of MCAO.[70] Gozes et al[71] have shown that intranasal administration of a Vasoactive Intestinal Peptide Analog (VIP analog, containing 28 amino acids) prevented learning and memory impairments resulting from cholinergic blockade in rats treated with aziridium. They also demonstrated that a nine amino-acid fragment of ADNF (ADNF-9) and an ANDF-like peptide (NAP) also protected against short-term memory loss in the same animal model.
Research in humans has also provided evidence of direct delivery of macromolecules to the CNS from the nasal cavity. Kern et al[72] have demonstrated CNS effects of intranasal corticotropin-releasing hormone (CRH) without altering plasma cortisol or CRH levels. Perras et al[73] have reported that intranasal delivery of growth hormone-releasing hormone (GHRH) not only increased rapid eye movement sleep and slow wave sleep in humans, but also decreased growth hormone.
Al-Ghananeem et al[74] carried out a study on the utility of the nasal route for delivery of 17b-estradiol, using its water-soluble prodrug. The study revealed that CSF concentration of 17b-estradiol following intranasal delivery of prodrug was higher compared to an equivalent intravenous dose. This result has a significant value in the treatment of Alzheimer's disease.
The efficacy of peptide/protein delivered intranasally is highly dependent on the molecular structure of the drugs and their size [MY NOTE: perhaps opioid peptides like dermorphin could be delivered this way]. Respiratory epithelial cells are capable of absorbing peptide/protein by a vesicular transport mechanism, followed by transfer to the extracellular spaces, and subsequent uptake by the submucosal vascular network.[75]

Delivery of DNA plasmids to the CNS
Of the several routes available for immunization, the nasal route is particularly attractive because of the ease of administration and the induction of potent immune responses, particularly in the respiratory tract. However, adjuvants and delivery systems are required to enhance immune responses following nasal immunization. The use of microparticles [poly(lactide co-glycolide)] as adjuvants and delivery systems for protein and DNA vaccines for nasal immunization were reviewed by Vajdy et al.[76] It has also been reported that after nasal administration of DNA plasmids, the level of plasmid in the brain was, 3.9 to 4.8 times higher than the plasmid concentration in the lungs and spleen. It was also found that the plasmid DNA reached the brain within 15 min following intranasal administration.[77] The higher distribution of plasmid to the brain after intranasal administration indicates that nasal administration might be a potential route for the delivery of therapeutic genes to the brain with reduced side-effects in the other organs. The plasmid administered in this study was very large as was the plasmid detected in the brain.

Delivery of small molecules to the CNS
Many small molecules have been shown to be transported directly to the brain and/or CSF from the nasal cavity. This has been reviewed by Illum[9] and Mathison et al.[11] Anand kumar et al[78] and David et al[79] have demonstrated intranasal delivery of estrogen and progesterone respectively, to the CSF. Studies have also shown that drugs such as L-NAME[80] and cocaine (at the lower end of the lipophilicity scale)[81] have a higher CSF and olfactory bulb concentration after nasal administration than that obtained after parenteral administration. The properties of small molecules, including size and lipophilicity affect delivery to the CNS following intranasal delivery.[82],[83],[84]
Sakane et al[85] reported that following intranasal administration of the antibiotic cephalexin to rats, higher CSF concentration was reached at 15 min but it declined to approximately half that concentration at 30 min. Because cephalexin does not cross the BBB well and because CSF concentration was 166-fold higher after intranasal administration than after systemic administration in spite of similar blood levels, it was concluded that cephalexin entered the CSF directly from the nasal cavity. Using a series of fluorescein isothiocyanate-labeled dextrans (FITC-dextran) with increasing molecular weights, it was found that dextrans with molecular weights of up to 20,000 daltons could be transported directly from the nasal cavity of rats into the CSF.[80] The concentration of the FITC-dextrans in the CSF increased with decreasing molecular weight. These FITC-dextrans are not found in the CSF after intravenous administration. Similarly, a comparison of the brain olfactory bulb concentrations achieved 30 min after intranasal administration of 7.4 n mol dopamine (153 daltons)[86] with those obtained after intranasal administration of 7.4 n mol nerve growth factor (NGF) (26,500 daltons)[16],[17] to rats, revealed a five-fold higher delivery of the lower molecular weight dopamine. Comparing the percentages of the original dose remaining in the brain 30 to 45 min after intranasal administration of dopamine (0.12%)[87] and NGF (0.023%)[32] in rodents revealed a similar difference. In addition, with most small molecules, a significantly higher molar dose can be delivered intranasally than with larger protein or DNA therapeutic agents. Thus, considerably higher concentrations of small molecules are achievable in the CNS with intranasal delivery. Ishikawa et al[88] reported that powder formulation of elcatonin utilizing CaCO3 improves the nasal bioavailability by increasing residence time in the nasal cavity and thus enhances the systemic bioavailability. Recently Bergstrom et al[89] studied the uptake of picolinic acid (PA) in the brain. [3H]PA was administered via unilateral nasal instillation or i.v. injection to mice. Autoradiography demonstrated rapid uptake of radioactivity in the olfactory nerve layer and in the ipsilateral olfactory bulb following nasal instillation, which was maintained at a high level even after 4 h. On the other hand i.v. injection of [3H]PA demonstrated selective uptake and retention of radioactivity in the olfactory bulb. Hussain et al[90] have found that intranasal administration of folic acid effectively results in complete and very rapid absorption into the CNS. This provides a method of rapidly and reliably delivering folic acid, alone or in combination with other compounds, to the systemic circulation to produce a beneficial effect in the treatment or prevention of Alzheimer's disease and stroke. Li et al[91]-reported rapid onset intranasal delivery of diazepam using ethyl-laurate-based microemulsion. At a 2 mg/kg dose, the maximum drug plasma concentration was arrived within 2-3 min, and the bio-availability (0-2 h) after nasal spray compared with i.v injection was about 50%. The results suggest that this approach may be helpful during emergency treatment of status epilepticus.
Illum et al[92] have studied the effect of chitosan-morphin nasal formulation vis-a-vis slow i.v. infusion of morphine in healthy volunteers who reported sedation at the earliest time point after nasal administration compared with i.v. administration. This suggests that after nasal administration morphine may be able to reach CNS more rapidly than after i.v. administration.


» Conclusion


In summary, the advantages of intranasal delivery are considerable. It is both rapid and non-invasive. It bypasses the BBB and targets the CNS, reducing systemic exposure and thus systemic side effects. Even for drugs that can cross the BBB, it can reduce systemic side effects by reducing the need for the drug to enter the systemic circulation. It does not require any modification of the therapeutic agent being delivered and should work for a wide range of drugs. Intranasal delivery may facilitate the treatment and prevention of many different neurologic and psychiatric disorders.

Paregoric Kid
03-13-2005, 11:32 PM
when I looked up the solubility of loperamide, many sites said that is was slightly soluble in water. (is this true, I have heard it is insoluble)
does anyone know if it is fat soluble?

peacefulwarrior
03-14-2005, 01:27 AM
does this article imply that intranasal administration of lopermadine might actually make lopermadine cross the bbb...if so wouldnt it already be abused much more recreationally? I couldn't get through it all the way.

There is a recent study done that shows that the bbb becomes much more permeable under stressful conditions...this is supposedly the cause of the gulf war syndrome since the chemical warfare antidotes soldiers were given actually crossed the bbb when they normally wouldnt because they were under stress. This may sound really dumb but does anyone know if its possible to acutely stress your body to make things like lopermadine cross? Would exercise work? If stress can do it then im sure the mechanism can be duplicated somehow maybe with chemicals. Right now it may sound a bit silly but I think this might be relevant after more research is done. Currently we think of ways to make the drugs more diffusable through the bbb but maybe we can consider keeping the drugs the same and making the bbb more permeable...

jacky
03-14-2005, 11:53 AM
A report discusses the blood plasma levels of loperamide and the three or four metabolites that actually cause much of loperamides effects. plasma levels can rise for up to 36 hours. I have felt obvious stimulation from 6 plus milligrams of loperamide, as well as additional effects liked increased reaction to other opiates and psychoactive effects. perhaps some of the metabolites are more lipid soluable, and that eventually the drug filters past the blood brain barrier over time, as it changes stucture, and rises in ratio to the blood. One study using 10 subjects who were all at one time opiate users stated that 1 of ten subjects felt euphoria from loperamide. that may be in line with the percentage of people who CAN feel euphoria from opiates, or it might just be a placebo effect resulting in endogenous release from opiates, or perhaps that one individual had somehow fooled the scientists and taken some other opiates in combo. there are so many variables and unknowns in human pharmacology....I look at my own experiences where I percieved an effects from consuming loperamide for days at a time. I would ususally take it while at work in the evening, for extra energy. I was also taking a combo of codeine and DXM. I thnik some psychoactive effects may be felt by SOME of the population, under the right coinditions. brain cells have been found in other parts of the body, especially the stomach. I try not to underestimate the potency of some drugs as well, looking at radiogram images of the plethora of opiate receptors that penetrate most parts of our body and substantial and evenly distributed patternsw that they form, and knowing just how many molecules can fit in a milligram or even micorgrams, there are plenty of places for even a microgram amount of molecules to end up hitching upon the right receptors. I think the potential of loperamide as a pain reliever, reducer of withdrawl symptoms, and psychoactive may become more apperant as the INTENTION of its use broadens. one opiophile who suffers from chronic pain used up to almost 200 milligrams of loperamide for pain control.

Paregoric Kid
03-14-2005, 12:39 PM
well I thought that too peaceful warrior, if it's been around this long someone had to have put it up their nose before. but even if that is true, there is certainly no reports of it that I could find. I searched google and bluelight and couldn't find any reports of insufflated loperamide. I think it could be that it sounds like such a stupid thing to do. you know, something that someone who is in that "gotta snort every god damn thing" phase. but really, if the above is true, that it might be possible to get past the bbb nasally, I think it is worth a shot. I might just have to go get a box of immodium today.

also, what about opiate peptides?

perhaps insufflating dermorphin or deltorphin for example would work

I used to use loperamide orally to potentiate opiates but I can't anymore because it causes too much constipation

jacky
03-14-2005, 03:09 PM
I think that peptides and such that can actually be sourced from more than a few companys have little use for illicit purposes...at least I have read this in some other posts in the old hive chemistry forum. in some way the bloodstream colelcts and binds these peptides in a way that makes it pretty imporbable that they would get past the bbb. now injecting them into specific parts of the brain or washing them over amputated receptors or cloned receptors is a different, and works for those who know what they are doing. I think that eventually some one will figure out how to stimulate peptide production with some sort of precursor or hormone is more probable than using the actual peptides, and potentially less of a risk legally..perhaps some sort of leucine binder or similiar idea would work to contribute to amino acids forming the peptide chains in the right places at the right times? I thought of the same thing too paragoric kid, and spent a few hours gazing at some relatively cheap dynorphine and other edorphines that were pretty well priced considering the alleged potency of the compounds. a few companys were satisfied with sending them to students of biology for R and D projects, NOT for consumption purposes obviously. maybe there are sources of some sort of steroidal component or similiar hormone stimulants that would end up increasing peptide production. I have heard of a type of magnetic (NON DRUG) procedure of simple magnetic fluctuations directly placed on the scalp causing significant endogenous opiate release, enough for U of Oregon to have a dept. working on it as a project slated for human trials and the whole FDA approval. I have not been able to find that dept project listed anymore, and can only remember that the paper I read was written by a female. I have read in various other places that this type of procedure is looming on the horizon in a big way, in a myriad or forms and intentions ,but perhaps inventors are more intent on selling the patents to the drug companys in the end....I would think that if such a thing happens a person still might be able to get plans and a kit for such a transcranial magnetic stimulation device that would probably be legal for an individual to use on themselves for religious or meditation purposes...maybe. A device that uses transcranial magnetic stimulation called the "Persinger helmet" is an amazing story and bit of research. studies of geomagnetic pulsations that were seeming to cause earthlights and other anomalys including alien contact and religious experience were taking place in a certian area that was being researched by a team of multidisciplinarians from a state college in the United States. geology, physics and psychology combined. the result was for geologists to provide data of significant magnetic pulses of a certian geological areas to the psychologists, who had built a device called the persingers helmet modeled on the data, hoping to recreate the conditions inside of a labratory controll room. Now I dont think this device actually can produce the well documented and scientifically explained earth lights, but what did happen was for HUMAN research subjects to explain bizarre feelings of contact with entitys, or the feeling that they were being watched by a presence, some felt religious experiences were associtated with their thoughts or feelings, and some of these experiences were visual and maybe even tactile I think. Depending on how you look at it it could be simply explained as only a figmint of imagination created by magnetic influence, or perhaps the conjecture that this is a type of dimensional transferance or experience created by magnetic forces that extends into a realm that we are unaware of? whatever it is I would think that the persinger helmet would be a hot research item, as would a device that releases endo opioids into the bloodstream, or even a mixture of BOTH at the same time. perhaps the persinger helmet creates religious experiences partly by way of endo opioid release, perhaps endo opioid release is a manifestation of a higher dimensional state at some point if a higher dimensional plane does exist...............perhaps the medicine buddha is a real physics force, and that miraculous healings are the procurement of magnetic influence upon the receptors and endocrine system by higher planed beings or a sort of collective "thought wave" created by the mass of human beings awarenesses. whatever the story is I want to try magnetic opioid production some day, in whatever country allows it. perhaps persinger helmets and virtual reality machines will someday create the disbelief suspension that a good movie might produce times 100,000, and at some point a reward pulse may provide opioid experiences without people having to actually puncture their body with needles and unsanitary black market drugs.

Paregoric Kid
03-14-2005, 03:42 PM
I read a report once of IV'd dermorphin, they said they definitly felt something but they thought it seemed "dirty" and not too strong, though this guy had a huge tolerance.

peacefulwarrior
03-14-2005, 03:44 PM
wow...interesting stuff. I work with the TMS (transcranial magnetic stimulation) machine that you talked about and, at least right now, isnt all that special for esoteric explanations. The magnetic field stimulates the ions to flow creating action potentials in the brain that are really just temporary lesions. It is not terribly specific and only works on the external layers of the brain. This means you can get a thumb to twitch while placing it over the motor cortex but but you cant really affect the reward systems and "good stuff". even if you use it on the occipital lobe or somatosensory area not much sensation is experienced except for maybe, MAYBE a few butterfly visual perceptions. Personally I would consider exercise, sex and coffee to release more endorphins than TMS but there's still a lot of research to be done. Some studies say it can help with depression and reminds us of the shock therapy treatment that used to be done for depression. Also, keep in mind that you cant really do the TMS pulsing for all that long or the brain may suffer from some forms of permanent damage/lesions. So right now everything is very limited.

As far as the "higher dimensional states"...we can talk for days about this in a very objective scientific manner. My area of interest in neuroscience is meditation and there is some very fascinating studies being done. My favorite is the studies that show meditation to be a completely different state entirely on its own (when compared to waking and dreaming states etc.) Transcendental Meditation is also particularly good for helping addiction. The studies are amazing and I would recommend meditation to anyone that is dealing with addictions.

jacky
03-16-2005, 12:56 AM
what about casein or casomorphin? thanks for the info P.warrior, keep up the stimulating at all costs! loperamide is a shitty tasting substance that leaves a strange sensation when it finally starts wearing off of mucous membranes, so perhaps extraction of the pills would be better than just crushing and snorting? I dont mind bitter stuff up the nose, but loperamide is a different sort of bitter.

peacefulwarrior
03-16-2005, 12:03 PM
despite the different sort of bitter...does intranasal administration seem to have recreational value? or at least more help from withdrawls than normal oral-digestive route?
i.e is it stronger?

Paregoric Kid
03-18-2005, 05:52 AM
I am really interested in the persinger helmet. you can buy one similar between $65-250 (the more expensive, the more features). it has a link to opiate effects on the website: http://www.innerworlds.50megs.com/shakti/index.htm
I'd like to learn more about the euphoric effects, there is so much info about the "spiritual" effects of meeting entities like a god or something, but not much about the opiate like effects that are possible.

SuperJunky
03-18-2005, 06:58 AM
If any one wants to get thier hands on some Loperamide HCL for further experimentation this might be the source. http://www.chemnet.com/show/fleminglab/eproduct/00001465.html

Paregoric Kid
03-19-2005, 08:24 PM
Drug Dev Ind Pharm. 2004 May;30(5):449-59.

pH dependent uptake of loperamide across the gastrointestinal tract: an in vitro study.

Crowe A, Wong P.

School of Pharmacy, Curtin University of Technology, Perth, Western Australia. a.p.crowe@curtin.edu.au

Loperamide is a peripherally acting antidiarrheal opioid with some affinity for P-glycoprotein (P-gp). One of the main reasons for its lack of central nervous system (CNS) activity is a combination first-pass metabolism and P-gp-mediated efflux preventing brain penetration. It was assumed that P-gp would also have a similar effect at the intestinal tract, limiting loperamide systemic absorption. However, previous in vitro studies had not determined loperamide flux using pH gradients present in the intestinal tract. Hence, our aim was to determine the influence of pH gradient conditions on the gastrointestinal uptake of loperamide, including any changes to its P-gp-mediated efflux. METHODS: Cellular uptake and transcellular transport were determined after exposure to various concentrations of loperamide (2-50 microM) with and without the presence of active efflux protein inhibitors. Loperamide was detected at 214 nm using high-performance liquid chromatography (HPLC) protocols. RESULTS: Bidirectional transport studies of 10 microM loperamide with a pH 6.0/7.4 apical (Ap)-to-basolateral (Bas) gradient showed efflux to be 17-fold higher than influx (10 ng/cm2/min Bas-->Ap compared to 0.6 for Ap-->Bas). This differential was much greater than when examined at pH 7.4/7.4 (only two-fold higher). The potent P-gp inhibitor, PSC-833, had only a moderate effect at blocking loperamide efflux under pH gradient conditions, yet could equilibrate bidirectional transport at pH 7.4. This suggested the presence of significant P-gp independent mechanisms, preventing loperamide access to the basolateral chamber. Amiloride and 5-(N-ethyl-N-isopropyl) amiloride had some effect on reducing efflux, hence the Na(+)--H(+) antiporter may have some involvement. Accumulation of loperamide into Caco-2 cells reduced almost 70% at pH 6.0 compared to pH 7.4, yet P-gp was always able to approximately double the equilibrium concentration in the cells within a defined pH study. This showed that P-gp was not affected by pH conditions. CONCLUSIONS: P-gp-mediated efflux of loperamide is supplemented under pH gradient conditions. Hence, drugs used to decrease acid secretion in the stomach could result in higher plasma loperamide levels based on our in vitro system reflecting the in vivo environment. The addition of a P-gp inhibitor could potentially further increase the gastrointestinal absorption of loperamide.

PMID: 15244080

moldie
03-20-2005, 01:10 AM
What about a reduction and dehalogenation of loperamide with iodine and phosophorous? The reduction should cetainly work, i'll have to check the difference in elctronegativity between chlorine and iodine before I can give any diffinitive statement about the dehalogenation. Wouldn't this new compound be an active analgesic?

I'm fairly cetain snorting loperamide will fail to yield analgesic activity in much the same way sudafed won't provide amphetamine-like activity. These two compounds have a lot in common actually.

peacefulwarrior
03-20-2005, 02:46 AM
Does anyone know what "P-gp inhibitors" are and any "drugs used to decrease acid secretion in the stomach"? haven't heard of these. Is the latter something like calcium carbonate?

moldie
03-20-2005, 04:11 AM
quinidine is an example of a substance that inhibits the p-glycoprotien. In fact studies have shown loperamide to be active at the 16mg level when adminstered IV with 600mg quinidine.

Paregoric Kid
03-20-2005, 05:07 AM
tagamet and grapefruit juice would slow the first pass metabolism
someone should try using tagament and/or grapefruit juice and dxm and snort loperamide, I'll probably end up trying it when I run out of things to do someday
everyone says try quinidine, but how do you get a hold of that stuff?

moldie
03-20-2005, 06:38 AM
quinidine is available either by prescription (in the US) or could be sourced from a chemical supplier. id go with a a chem supplier because I doubt you would be able to convince a doctor that you have malaria. contrary to the belief of some quinine will not work as a substitute, i've tried it.

Klot
03-25-2005, 04:52 AM
Complex with ascorbic acid may to help

tread from old HIVE

kreo
(Stranger)
07-17-02 20:10
No 333910

loperamide question?
Bookmark

recently swim had a dream. the dream proceeds as follow: swim aquired 6mg loperamide hcl. swim decided to poor 20ml dilute acetic acid ~5% making it a ~1:1 mole ratio. nothing was happening so swim decided to chunk in an acid (ascorbic acid ~125mg), didnt have any sulfuric acid, just for shits and gigles the solution turned a deep orange color. prior knowledge tells swim that the orange is from the precense of dehydroascorbate, the oxidized form of ascorbic acid. the resulting product had strong opiate like effects in the microgram dose. swim would like to know what the hell happened since swim wasnt expecting much. swim thinks it just formed an acetic ester but swims confused on what the ascorbic acid did. would any bee mind helping swim out with his problem?
im an artist. i look at things from a creative perspective.
peace out


Dr_Heckyll
(Stranger)
07-17-02 20:52
No 333927

Question
Bookmark

the resulting product had strong opiate like effects in the microgram dose.
How did swim determine that?

Dr. Heckyll & Mr. Jive by Men at Work
...tells my tale.

kreo
(Stranger)
07-18-02 10:45
No 334193

swim has EXTREMELY limited improvised resources ...
Bookmark

swim has EXTREMELY limited improvised resources and equiptment due to a nosy three lettered freind. as for the bioassay swim just railed a tiny tiny line of the crude product ~.025-.05mg its hard for swim to tell by eye especially seeing that an unknown percentage is crude byproducts. the previous dose had effects similer to ~7.5mg hydrocodone not to mention crazy ass itching. swim is cautious of experimenting further without further knowledge on what sort of "frankendrug" was producted, even swims got limits on how far swim pushes swims body.
im an artist. i look at things from a creative perspective.
peace out


foxy2
(Distinctive Doe)
07-18-02 11:34
No 334205

well probably nothing
Bookmark

I have read an article that stated snorting drugs can directly bypass the blood-brain barrier, to a limited extent.

I forget the details.
Those who give up essential liberties for temporary safety deserve neither liberty nor safety


kreo
(Stranger)
07-18-02 13:38
No 334240



swim says insufflated loperamide is extremely ...
Bookmark

swim says insufflated loperamide is extremely unpleasant, it takes ~6mg to feel threshold effects, it makes swims nose itch like hell and swell up, and its got a lot of toxic side effects, eg. facial swelling, profuse sweating, itching. swims face and hands were breaking out for about a week while swim only felt threshold effects for the first few hours. maybe it was a placebo but the toxic effects were very real. swims freinds thought swim was being attacked by a flesh eating bacteria.
im an artist. i look at things from a creative perspective.
peace out


foxy2
(Distinctive Doe)
07-18-02 14:16
No 334248

opiate
Bookmark

Those sound like opiate side effects. Which is typically all you get from loperamide, and thus its otc.

Maybee whatever you insuffelated with it caused the permiability of your membranes to increase.

Or your full of shit.
I'll flip a coin.

Tails, I think your full of shit.

The scientific method at its finest
Those who give up essential liberties for temporary safety deserve neither liberty nor safety

carboxyl
(Hive Bee)
07-18-02 14:49
No 334269


am i getting this right?
Bookmark

so you took some otc loperamide, tossed it in some vinegar, threw in some vitamin c, and got a compound active at
.025-.05 mg??? Doesn't it sound a little bit far fetched? I think I'm with foxy on this one, but please correct me if i'm wrong
The above post is purely fictional. Any resemblance to "real-life" is purely coincidental.


kreo
(Stranger)
07-18-02 16:01
No 334312


yeah dude swim thought it was pretty far fetched ...
Bookmark

yeah dude swim thought it was pretty far fetched too. swim cant really rule out that there might have been impurities in the reaction vessel or that swim has abnormal sensitivity to certain chemicals. so swim was hoping someone on the forum might be able to duplicate the result seeing that niether chemistry nor psychoactive substances are swims area of expertise. swim let it react in room temperature for two days.
im an artist. i look at things from a creative perspective.
peace out



kreo
(Stranger)
07-18-02 16:17
No 334320


swim doesnt think swim made 'swimself' clear but ...
Bookmark

swim doesnt think swim made 'swimself' clear but on the post where swim was describing effects, swim was refering to insufflated loperamide NOT 'frankendrug'. swim wants some feedback on this. maybe a response of a more chemical or biological nature would be a little more helpful.
im an artist. i look at things from a creative perspective.
peace out


Dr_Heckyll
(Stranger)
07-18-02 19:45
No 334395


Shit or not shit?
Bookmark

Any articles about ascorbic acid and other drug

Design, Synthesis and Activity of Ascorbic Acid Prodrugs of Nipecotic, Kynurenic and Diclophenamic Acids, Liable to Increase Neurotropic Activity

Stefano Manfredini,* Barbara Pavan, Silvia Vertuani, Martina Scaglianti, Donatello Compagnone, Carla Biondi, Angelo Scatturin, Sergio Tanganelli, Luca Ferraro, Puttur Prasad, and Alessandro Dalpiaz

Department of Pharmaceutical Sciences, via Fossato di Mortara 19, 44100 Ferrara, Italy, Department of Biology, General Physiology Section, via Borsari 46, 44100 Ferrara, Italy, and Department of Experimental Clinical Medicine, Pharmacology Section, via Fossato di Mortara 19, 44100 Ferrara, Italy, and Department of Obstetrics and Gynecology, Medical College of Georgia, Augusta, GA

Received July 26, 2001

Abstract:

To improve the entry of certain drugs into brain, ascorbic acid (AA) conjugates of these drugs were synthesized and their capacity to interact with SVCT2 ascorbate transporters was explored. Kinetic studies clearly indicate that all of the conjugates were able to competitively inhibit ascorbate transport in human retinal pigment epithelial cells (HRPE). In vivo studies, in a mouse model system, demonstrate that conjugate 3 is better absorbed compared to the nonconjugated parent drug.

http://pubs.acs.org/cgi-bin/abstract.cgi/jmcmar/2002/45/i03/abs/jm015556r.html

Research Article

Transporter-mediated effects of diclofenamic acid and its ascorbyl pro-drug in the in vivo neurotropic activity of ascorbyl nipecotic acid conjugate
Alessandro Dalpiaz 1 *, Barbara Pavan 2, Martina Scaglianti 1, Federica Vitali 1, Fabrizio Bortolotti 1, Carla Biondi 2, Angelo Scatturin 1, Sergio Tanganelli 3, Luca Ferraro 3, Puttur Prasad 4, Stefano Manfredini 1
1Department of Pharmaceutical Chemistry, via Fossato di Mortara 19, 44100, Ferrara University, I-44100 Ferrara, Italy
2Department of Biology, General Physiology Section, via Borsari 46, Ferrara University, I-44100 Ferrara, Italy
3Department of Clinical and Experimental Medicine, Pharmacology Section, via Fossato di Mortara 19, 44100, Ferrara University, I-44100 Ferrara, Italy
4Department of Obstetrics and Gynecology, Medical College of Georgia, Augusta, Georgia

email: Alessandro Dalpiaz (dla@dns.unife.it)

*Correspondence to Alessandro Dalpiaz, Department of Pharmaceutical Chemistry, via Fossato di Mortara 19, 44100, Ferrara University, I-44100 Ferrara, Italy. Telephone: 390532-291273; Fax: 390532-291296

Keywords
active transport • ascorbic acid • CNS • diclofenamic acid • nipecotic acid • prodrugs • stability • SVCT2 • transporters

Abstract
Continuing our studies on SVCT2 ascorbic acid (AA) transporter-mediated drug delivery of neurotropic agents, we have now investigated the in vitro intracellular uptake of Diclofenac (Diclo) and its conjugate (AA-Diclo), both characterized by high affinity for the SVCT2 transporter. We have also investigated the in vivo uptake mechanism of AA-conjugate of Nipecotic acid (AA-Nipec) and the implication of the transporter-mediated effects of Diclo and AA-Diclo. Diclo resulted as a noncompetitive inhibitor of AA transport, but also showed a sodium-dependent and ascorbate-independent uptake, thus implying the possible involvement of specific transporters in the delivery to the brain of Diclo. This result opens a perspective in the discovery of new strategies in the targeting of this drug to the brain. Inhibitory effects of Diclo and AA-Diclo on the SVCT2 transporter were used to study anticonvulsant effects of AA-Nipec, confirming our hypothesis of an SVCT2-mediated transport in its neurotropic activity. AA-Diclo stability has been also investigated: it is hydrolyzed following a first-order kinetics in buffer, plasma (t1/2 at about 10 h) and whole blood (t1/2 at about 3 h), suggesting AA-Diclo as a potential candidate to enhance the short half-life of Diclo in vivo. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:78-85, 2004
Received: 18 May 2003; Revised: 28 July 2003; Accepted: 28 July 2003

Digital Object Identifier (DOI)

10.1002/jps.10532 About DOI

http://www3.interscience.wiley.com/cgi-bin/abstract/106561774/ABSTRACT

European Journal of Pharmaceutical Sciences
Volume 24, Issue 4 , March 2005, Pages 259-269

doi:10.1016/j.ejps.2004.10.014
Copyright © 2004 Elsevier B.V. All rights reserved.

Ascorbic and 6-Br-ascorbic acid conjugates as a tool to increase the therapeutic effects of potentially central active drugs

Alessandro Dalpiaza, , , Barbara Pavanb, Silvia Vertuania, Federica Vitalia, Martina Scagliantia, Fabrizio Bortolottia, Carla Biondib, Angelo Scatturina, Sergio Tanganellic, Luca Ferraroc, Giuliano Marzolac, Puttur Prasadd and Stefano Manfredinia

aDepartment of Pharmaceutical Sciences, Ferrara University, via Fossato di Mortara 19, 44100 Ferrara, Italy
bDepartment of Biology, General Physiology Section, via Borsari 46, 44100 Ferrara, Italy
cDepartment of Experimental Clinical Medicine, Pharmacology Section, via Fossato di Mortara 19, 44100 Ferrara, Italy
dDepartment of Obstetrics and Gynecology, Medical College of Georgia, Augusta, GA, USA

Received 14 April 2004; revised 15 October 2004; accepted 25 October 2004. Available online 18 December 2004.



Abstract

Ascorbic acid (AA) or 6-Br-ascorbate (BrAA) conjugation has been investigated as a tool to improve brain drug delivery by the Vitamin C transporter SVCT2. To this aim, the effects of AA- or BrAA-conjugation on drug affinity and uptake have been assessed in vitro, by using human retinal pigment epithelium (HRPE) cells, and compared in vivo on mice. Nipecotic, kynurenic and diclofenamic acids were chosen as model drugs. Kinetic and inhibition experiments referred to [14C]AA uptake into HRPE cells showed that nipecotic and kynurenic acids became able to interact with SVCT2, as competitive inhibitors, only when conjugated to AA or BrAA. Surprisingly, diclofenamic acid itself appeared able to interact with SVCT2, with an affinity that was significantly increased or decreased by AA or BrAA conjugation, respectively. HPLC analysis, performed on HRPE cells, confirmed the SVCT2 mediated transport for the BrAA-conjugate of nipecotic acid, whereas kynurenic acids conjugates although interacting with the transporter did not enter the cells. In accordance, only the nipecotic acid conjugates showed anticonvulsant activity after systemic injection in mice.

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T25-4F29SYD-2&_coverDate=03%2F01%2F2005&_alid=260224233&_rdoc=1&_fmt=&_orig=search&_qd=1&_cdi=4909&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=a30836763475b4e119918190da0d22ca

: Int J Pharm. 2005 Mar 3;291(1-2):171-81. Epub 2004 Dec 30.

Vitamin C and 6-amino-vitamin C conjugates of diclofenac: synthesis and evaluation.

Dalpiaz A, Pavan B, Scaglianti M, Vitali F, Bortolotti F, Biondi C, Scatturin A, Manfredini S.

Dipartimento di Scienze Farmaceutiche, Universita di Ferrara, via Fossato di Mortara 19, 44100 Ferrara, Italy. dla@dns.unife.it

Diclofenac (Diclo), its ascorbic acid (AA) or 6-amino-AA (AA-NH2) pro-drugs (AA-Diclo or AA-NH-Diclo) were prepared and evaluated on human retinal pigment epithelium (HRPE) cells to investigate their ability to interact with the vitamin C transporter SVCT2 and their cellular uptake. Furthermore, stabilities in physiological fluids of these compounds were investigated. For kinetic experiments, AA-Diclo was incubated in Tris-HCl buffer, human plasma or whole blood. The extracted samples were analysed by HPLC. AA-Diclo was hydrolysed following first order kinetics in buffer, plasma (t1/2 about 10 h) and whole blood (t1/2 about 3.5 h). Transport and inhibition assays were performed by adding [14C]AA and the above-mentioned unlabelled compounds to plated HRPE cells. Intracellular accumulation was measured incubating HRPE cells with increasing concentrations of unlabelled compounds, following by HPLC analysis. Diclo resulted as a non-competitive inhibitor of AA-transport, showing a Na+-dependent and ascorbate-independent uptake. AA-Diclo behaved as a competitive inhibitor, but it was not transported into cells, whereas its analogue AA-NH-Diclo showed a decreased inhibitory activity. Stability studies suggest AA-Diclo as a potential candidate to enhance the Diclo short half life in vivo. The discovery of a Na+-dependent transporter for Diclo on HRPE cells opens new perspectives for targeting diclofenac into the brain.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15707744

J Pharm Sci. 2004 Jan;93(1):78-85.

Transporter-mediated effects of diclofenamic acid and its ascorbyl pro-drug in the in vivo neurotropic activity of ascorbyl nipecotic acid conjugate.

Dalpiaz A, Pavan B, Scaglianti M, Vitali F, Bortolotti F, Biondi C, Scatturin A, Tanganelli S, Ferraro L, Prasad P, Manfredini S.

Department of Pharmaceutical Chemistry, via Fossato di Mortara 19, 44100, Ferrara University, I-44100 Ferrara, Italy. dla@dns.unife.it

Continuing our studies on SVCT2 ascorbic acid (AA) transporter-mediated drug delivery of neurotropic agents, we have now investigated the in vitro intracellular uptake of Diclofenac (Diclo) and its conjugate (AA-Diclo), both characterized by high affinity for the SVCT2 transporter. We have also investigated the in vivo uptake mechanism of AA-conjugate of Nipecotic acid (AA-Nipec) and the implication of the transporter-mediated effects of Diclo and AA-Diclo. Diclo resulted as a noncompetitive inhibitor of AA transport, but also showed a sodium-dependent and ascorbate-independent uptake, thus implying the possible involvement of specific transporters in the delivery to the brain of Diclo. This result opens a perspective in the discovery of new strategies in the targeting of this drug to the brain. Inhibitory effects of Diclo and AA-Diclo on the SVCT2 transporter were used to study anticonvulsant effects of AA-Nipec, confirming our hypothesis of an SVCT2-mediated transport in its neurotropic activity. AA-Diclo stability has been also investigated: it is hydrolyzed following a first-order kinetics in buffer, plasma (t(1/2) at about 10 h) and whole blood (t(1/2) at about 3 h), suggesting AA-Diclo as a potential candidate to enhance the short half-life of Diclo in vivo. Copyright 2004 Wiley-Liss, Inc.


PMID: 14648638 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14648638


May be its right ? :)

jacky
03-25-2005, 06:36 PM
well, I dont think that I will be snorting any loperamide soon. but it would be a very interesting thing if this ascorbic acid transport is a possible deal. perhaps orally this mix would create a different effect? perhaps some DMSO or IV ideas come to mind?

Va_va
06-07-2005, 08:20 AM
Loperamide crossing the blood brain barrier with the assistance of ascorbic acid ?

Or have i completley lost the plot ?

Va_va
06-14-2005, 02:48 PM
Dont know if this will be of any help, think i have lost the plot but here . . . .

http://www.health-marketplace.com/Grape-Seed-Extract.htm

This stuff is one hundread times more potent than vitamin c and fifty times more than vitamin e
and it says this - Cross the blood brain barrier to provide potent antioxidant protection to brain and spinal nerves.

Dont know if that means anything

doctor diesel
06-18-2005, 02:02 AM
Does anyone know what "P-gp inhibitors" are and any "drugs used to decrease acid secretion in the stomach"? haven't heard of these. Is the latter something like calcium carbonate?

Drugs used to decrease acid secretion in the stomach are known as Proton-Pump Inhibitors. They are widely available and include the active chemicals famotidine, ranitidine, cimetidine, lansoprazole. Popular trade names you may recognise include: Losec, Zantac, Zoton, Tagamet, Peptid AC (I think) and many more.... Yhey reduce the stomach's production of hydrochloric acid by about 80%, which leaves plenty still for digesting food, but no excess to crawl up your oesophagus and burn it.

Diesel

kramorph
06-22-2005, 06:37 PM
Hate to be a smart ass Doctor Deisel, but Zantac,tagamet and other otc heartburn meds are histamine 2 inhibitors, they prevent histamine from stimulating the proton pump to increase acid.Losec and Zoton are proton pump inhibitors. The ppump inh. are better as i found with zantac et al. creates a rebound acidity when you stop them and tolerance develops quickly, but Zoton et al works better for longer without the rebound effects.(I should have been a pharmacist but found morphine just before I finished lol).

bogumil
01-22-2006, 07:06 PM
I found that about Loperamide (active ingredient in Immodium, derivated from the morphine molecule. An opioid, which doesnt cross the blood-brain-barrier).

"

>Increased drug delivery to the brain by P-glycoprotein inhibition
>Background: Although the antidiarrheal loperamide is a potent opiate, it



does not produce opioid central nervous system effects at usual doses in
patients. On the >basis of in vitro studies demonstrating that loperamide is
a substrate for the adenosine triphosphate-dependent efflux membrane
transporter P-glycoprotein, we >postulated that inhibition of P-glycoprotein
with quinidine would increase entry of loperamide into the central nervous
system with resultant respiratory depression.
>Methods: To test this hypothesis, a 16-mg dose of loperamide was



administered to eight healthy male volunteers in the presence of either 600
mg quinidine, a >known inhibitor of P-glycoprotein, or placebo. Central
nervous system effects were measured by evaluation of the respiratory
response to carbon dioxide >rebreathing as a measure of opiate-induced
respiratory depression.
>Results: Loperamide produced no respiratory depression when administered



alone, but respiratory depression occurred when loperamide (16 mg) was given
with >quinidine at a dose of 600 mg (P < .001). These changes were not
explained by increased plasma loperamide concentrations.
>Conclusion: This study therefore demonstrates first the potential for



important drug interactions to occur by a new mechanism, namely, inhibition
of P->glycoprotein, and second that the lack of respiratory depression
produced by loperamide, which allows it to be safely used therapeutically,
can be reversed by a >drug causing P-glycoprotein inhibition, resulting in
serious toxic and abuse potential. (Clin Pharmacol Ther 2000;68:231-7.)
Does this mean coadministration of Imodium with quinidine can also produce
potent analgesia???
"

SomniGod
01-22-2006, 08:08 PM
Maybe Regis has something to add here?
I can tell you that I am extremely interested in acquiring a method to help L across the BBB!!


~S~

exitwound
01-22-2006, 08:09 PM
You've got it exactly right. Loperamide is a remarkable OTC medication!

Poor man's methadone, it has often been called. Takes most of the physical symptoms of W/D away, but not the nerve/brain/psychological symptoms, sadly.

As you say, it doesn't cross the BBB. Many have tried to get around this somehow, and all have failed. That's why it's still over the counter!

SomniGod
01-23-2006, 01:16 PM
I think the question here is can we HELP it across?
I know I would gladly walk an ol lady across the street...in turn I would gladly walk 200mg of Lop across the BBBthreshold...shit I'd carry it across if I could!!!


~S~

Coddfish
01-25-2006, 02:36 AM
wtf is quinidine, and where do I get it? Not something that can be gleaned from the herb section of the health food store I gather?

BTW, where the f am I when these studies happen? Anyone ever participated in an opiate/drug study/experiment? Report please.

katomic
01-25-2006, 08:35 AM
anti merlera (sp?) drug in it? its in tonic water in tiny amounts

shaunclo
01-25-2006, 12:59 PM
There was an old post where Paregoric Kid, and Zoop were giving the old college try with no avail. I cant remember the name of the post, but it was like 3 pages long with anything and everthing covered about this Immodium thing. I personally think that if it could be done, it would have been done by now. Not to give up or anything, I just think we are beating a dead-horse to death again. I am going to try and find that thread and I will post the name of it here soon.

exitwound
01-25-2006, 02:23 PM
There was an old post where Paregoric Kid, and Zoop were giving the old college try with no avail. I cant remember the name of the post, but it was like 3 pages long with anything and everthing covered about this Immodium thing. I personally think that if it could be done, it would have been done by now. Not to give up or anything, I just think we are beating a dead-horse to death again. I am going to try and find that thread and I will post the name of it here soon.

Yeah, sadly I've seen this horse flogged straight into the ground many times over. I really don't think there's much point bothering since getting loperamide to cross the BBB is like the junkie's holy grail....Unobtainium, basically.

SomniGod
01-25-2006, 04:38 PM
where there's a will there's a way....it's finding an EASY way that's tricky! I am fully against throwing the idea out...maybe just put it on a back burner till something comes up that makes sense to try with this venture.

~S~

Mokelly
01-25-2006, 05:18 PM
I've gotten high as hell of of immodium! I shoot it all the time!

Mokelly
01-25-2006, 05:19 PM
April Fools!,............wait a tick.....crap nm

Coddfish
01-26-2006, 02:32 AM
anti merlera (sp?) drug in it? its in tonic water in tiny amounts
I think that's quinine, but maybe the same thing or related? If it's the same thing, it should be easy to get. i would like to look at that thread, shaunclo. I'll look, but if you find it, please post.
You know, if those guinea pigs abve can get high, what's to stop a few of the most resourceful people in the world from 'reproducing the experiement?'

katomic
01-26-2006, 02:58 AM
I was close

QUINIDINE [quinidine] , heart muscle relaxant used to maintain regular heart rhythm patterns. It is an alkaloid (http://www.encyclopedia.com/html/a/alkaloid.asp) chemically similar to quinine (http://www.encyclopedia.com/html/q/quinine.asp) and, like quinine, occurs naturally in some species of cinchona trees. Quinidine slows the rate of blood flow in heart chambers and lowers the excitability of the muscle. Quinidine is a general relaxant of smooth muscle and acts as a dilator of larger blood vessels. It has also been used to reduce fever and to treat malaria. Synchronized electric shock has largely replaced quinidine as a method of establishing more normal heart rhythms

Coddfish
01-26-2006, 03:13 AM
Good info. Maybe quinine would do the trick. Anyone tried it? Any takers?

exitwound
01-26-2006, 01:24 PM
Quinine and Quinidine are two different things....I know their spelling is similar so it's easy to mistake them for each other, though.

bogumil
01-26-2006, 01:45 PM
Thing is, when loperamide is derived from morphine, as I understood it, they use morphine as precusor? Then the reaction can be driven back. question would only be the amount of work and chemical skills needed. And, of course, if morphine is only a blueprint for the molecule and they sythesized it from something else, then there probably is no chance.

I think it would be enough if the original, very first time loperamide, was manufactured from real morphine. If they later make it up from other precusors, dont matter. The molecule should be the same. And then one can for sure go back from loperamide to morphine. But like I said, if it is too much chemicals and skills needed...

JoyDivision
01-27-2006, 07:19 AM
http://en.wikipedia.org/wiki/Quinidine

Quinidine is a pharmaceutical (http://en.wikipedia.org/wiki/Pharmaceutical) agent (http://en.wikipedia.org/wiki/Medication) that acts as a class I antiarrhythmic agent (http://en.wikipedia.org/wiki/Antiarrhythmic_agents) in the heart (http://en.wikipedia.org/wiki/Heart). It is a stereoisomer (http://en.wikipedia.org/wiki/Stereoisomer) of quinine (http://en.wikipedia.org/wiki/Quinine), originally derived from the bark of the cinchona (http://en.wikipedia.org/wiki/Cinchona) tree.

Stereoisomerism is the arrangement of atoms (http://en.wikipedia.org/wiki/Atom) in molecules (http://en.wikipedia.org/wiki/Molecule) whose connectivity remains the same but their arrangement in space is different in each isomer (http://en.wikipedia.org/wiki/Isomer).

So Quinidine and Quinine are pretty much the same shit. Kind of like Lexapro and Citalopram or Dramamine and Benydrl.

Look Immodium is nothing more than an effective drug for opiate withdrawl symptoms or a runny bum. Let's leave it as that. Or let the people with chemistry degrees figure it out.

Zoops
01-27-2006, 08:47 AM
Thing is, when loperamide is derived from morphine, as I understood it, they use morphine as precusor? Then the reaction can be driven back. question would only be the amount of work and chemical skills needed. And, of course, if morphine is only a blueprint for the molecule and they sythesized it from something else, then there probably is no chance.

I think it would be enough if the original, very first time loperamide, was manufactured from real morphine. If they later make it up from other precusors, dont matter. The molecule should be the same. And then one can for sure go back from loperamide to morphine. But like I said, if it is too much chemicals and skills needed...

Loperamide is not made from morphine. It is totally synthetic. It is chemically similar to meperidine, which is also completely synthetic.

Click here to look at the structure of loperamide:

http://chem.sis.nlm.nih.gov/chemidplus/

type in loperamide and then press "search"

US patent 3714159 tells how they make it. www.uspto.gov (http://www.uspto.gov) gives access to US patents, anyone can read it if they care to.

someday, I think we will break the code on this shit. and then , it'll promptly be made a controlled substance.

shaunclo
01-27-2006, 10:15 AM
Okee-Doe-Kee, Zoop found the old thread and PM'd me it.

Here it is http://forum.opiophile.org/showthread.php?t=929&highlight=loperamide+acetic+anhydride

We were all going nuts trying to figure a way to do this, you need pure Loperamide though, which Zooper was trying to get his hands on. I believe he is still trying.

bogumil
01-27-2006, 10:51 AM
... Look Immodium is nothing more than an effective drug for opiate withdrawl symptoms or a runny bum. Let's leave it as that. Or let the people with chemistry degrees figure it out.

Yeah, I think youre right, one should probably leave it at his. The bees would probably already have done it. But then, maybe they didnt care about it much?



... Loperamide is not made from morphine. It is totally synthetic. It is chemically similar to meperidine, which is also completely synthetic.
Do you mean, it never was made from morphine? I too am pretty sure, that now it is synthesized. What I meant was: When loperamide was "invented", they maybe experimented with morphine molecules and created loperamide this way. Then they looked for cheaper ways to produce loperamide on a large scale and found that synthsizing is cheaper. Since that loperamide is synthesized. Thats what I meant. Only the very first time, the molecule was created, did they create it from morphine then? Because if this was the case, then there would be a way from one molecule to the other ... But you probably meant the same, or? Maybe one can find the patent for the first loperamide somewhere?

Edited: Zoop, I just read the thread. You seem to have a good practice and knowledge in opie-chem? I fear then, if you say that it wont work, that then there really isnt a way ...

Zoops
01-28-2006, 02:00 AM
Yeah, I think youre right, one should probably leave it at his. The bees would probably already have done it. But then, maybe they didnt care about it much?



Do you mean, it never was made from morphine? I too am pretty sure, that now it is synthesized. What I meant was: When loperamide was "invented", they maybe experimented with morphine molecules and created loperamide this way. Then they looked for cheaper ways to produce loperamide on a large scale and found that synthsizing is cheaper. Since that loperamide is synthesized. Thats what I meant. Only the very first time, the molecule was created, did they create it from morphine then? Because if this was the case, then there would be a way from one molecule to the other ... But you probably meant the same, or? Maybe one can find the patent for the first loperamide somewhere?

Edited: Zoop, I just read the thread. You seem to have a good practice and knowledge in opie-chem? I fear then, if you say that it wont work, that then there really isnt a way ...

As far as loperamide's research and development goes, I have studied the literature and it was originally derived as part of the efforts to develop new synthetic opiates, inspired from the earlier work done with meperidine. Meperidine was discovered accidentally - the people who discovered it were trying to make some other type of drug and had no idea that the substance had opiate activity. I think they were investigating anticonvulsants. When meperidine was administered to the test animals (mice or rats), they observed a telltale opiate response, called the "Straub reaction," named after some German cat who discovered that morphine and other opiates caused a peculiar and unique reaction in rats and mice, where their tails get stiff and take on an "S" shape. they walk around with that silly stiff tail. They only do this when on opiates, so when meperidine caused this in the test animals, they knew they had an opiate on their hands.

sometime after that, it was observed by others that the meperidine molecule is indeed a VERY stripped-down morphine molecule. I wish I could paste some molecular structures here to show everyone what I mean. Well, loperamide was developed during the early 70's at the end of a period of time, beginning in the late 50's early 60's that began when meperidine was discovered. Chemists were busily making new phenyl-piperidine compounds in search of new and more potent opiates. Fentanyl and its cousins were invented as a result of the original work with meperidine as well - and as everyone knows, fentanyl derivatives are the strongest opiates. Sufentanyl is my dream opiate - if I could get my hands on a few ounces of pure sufentanyl, I would be SET FOR LIFE, literally - only about 50 to a 100 micrograms is needed (100 only if you have a monstrous tolerance) for a heavy hit of that shit. It's beautiful. I worked in a hospital pharmacy briefly, about 9 years ago, and I got to shoot up 50ug of sufenta on several occaisons (sp?). Nice. Very very nice indeed.

So, loperamide is sort of distantly related chemically to morphine, but it was never made from any morphine or anything like that.

I still think that acetylated loperamide would be a good opiate, because of the experiments with compounds that enable it to cross the BBB where they show that it does act like an opiate when that happens. acetylation would make the molecule more lipophilic, by masking that ugly hydroxyl group, and thereby enabling the BBB crossing. Shit, if only we could find a source for pure loperamide. I e-mailed a chem company in China, yet again, telling them that I want to purchase a small lot of loperamide, like 5 to 10 grams of it, for my "company." that would be enough to make 2,500 to 5,000 tablets of immodium at 2mg each!

Coddfish
01-28-2006, 04:06 AM
May the schwartz be with you, Zoop. Here's hoping you give it the old college try. Even if the stuff did end up as a schedule III or IV, everyone on this site would be set for life before any laws were passed. This is worthwhile; as someone said, the 'holy grail.' I still wonder about quinine vs. quinidine. Isomers can share many of the same characteristics as their brothers. Someone tell me I'm not making sense.

katomic
01-28-2006, 11:04 AM
over at synthetikal thay where talking of the dehalogenation of loperamide and never mentioned acetilzing (sp?) it one also seid maybe the bees where keeping it to themselves so not to get it banned.

is loperamide soluble in water?

katomic
01-28-2006, 11:09 AM
over at synthetikal thay where talking of the dehalogenation of loperamide and never mentioned acetilzing (sp?) it one also seid maybe the bees where keeping it to themselves so not to get it banned.

is loperamide soluble in water?

bogumil
01-28-2006, 11:32 AM
"Straub reaction," named after some German cat who discovered that morphine and other opiates caused a peculiar and unique reaction in rats and mice, where their tails get stiff and take on an "S" shape. they walk around with that silly stiff tail. They only do this when on opiates,

Dude, thats hilarious. But dont all we opie users kind of walk with a stiff tale when we see beautiful opiates? :D I was wondering several times, if it is possible to order something as a company. Cause when I see what they offer on those pharma sites, like opium, morphine, fenta, codi, cocaine just everything one could wish, all in the kilo-range. Unbelievable. I was wondering if normal pharmacies are allowed to order on such sites?
If I ever run across some pure loperamide I will let you know for sure. Until then, cant one just do an extraction like with ephedrine? I mean people produce good stuff fromo pill ephedrine. So if one extracted some packs of loperamide, one might get a relatively pure basis for some experiments. On that one then could run all the standard operations that can be done on an opiate, like acetylation, halogenation, and whatever I dont know even exists. lol





over at synthetikal thay where talking of the dehalogenation of loperamide and never mentioned acetilzing (sp?) it one also seid maybe the bees where keeping it to themselves so not to get it banned. ... is loperamide soluble in water?

Who knows, maybe a part of the morphine and heroin sold on the street is already made from loperamide! lol No, really, sounds possible to me, that they keep a very useful thing for themselfes, but sooner or later someone maybe will break the rules (if they found something).

SomniGod
01-28-2006, 01:32 PM
watch someone get sniped....the thread mysteriously disappears.... we caught on to their secret!!!

LOL



~S~

bogumil
01-31-2006, 05:08 AM
Central analgesic actions of loperamide following transient permeation of the blood brain barrier with Cereport

The bradykinin analog, Cereport (RMP-7), was designed to increase permeability of the blood brain barrier (BBB). ... Cereport was able to increase delivery of loperamide across the BBB, allowing it to gain access to opiate receptors in the CNS to produce a centrally mediated analgesic effect."
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9729419&query_hl=7&itool=pubmed_DocSum


Variable modulation of opioid brain uptake by P-glycoprotein in mice.

"The efflux transporter P-glycoprotein (P-gp) is an important component of the blood-brain barrier (BBB) that limits accumulation of many compounds in brain. Some opioids have been shown to interact with P-gp in vitro and in vivo. Genetic or chemical disruption of P-gp has been shown to enhance the antinociceptive and/or toxic effects of some opioids ... influence of mdr1a P-gp on initial brain uptake of chemically diverse opioids in mice. ... The difference in brain uptake between P-gp-competent and P-gp-deficient mice ranged from no detectable effect (meperidine) to >/=8-fold increase in uptake (DPDPE, loperamide, and SNC 121). In addition, loperamide efflux at the BBB was inhibited by quinidine. ... The variable influence of P-gp on opioid brain distribution may be an important issue in the context of pharmacologic pain control and drug interactions. "
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14698039&query_hl=2&itool=pubmed_docsum



Increased drug delivery to the brain by P-glycoprotein inhibition.

BACKGROUND: Although the antidiarrheal loperamide is a potent opiate, it does not produce opioid central nervous system effects at usual doses in patients. ... we postulated that inhibition of P-glycoprotein with quinidine would increase entry of loperamide into the central nervous system ... RESULTS: Loperamide produced no respiratory depression when administered alone, but respiratory depression occurred when loperamide (16 mg) was given with quinidine at a dose of 600 mg (P < .001). These changes were not explained by increased plasma loperamide concentrations. CONCLUSION: This study therefore demonstrates first the potential for important drug interactions to occur by a new mechanism, namely, inhibition of P-glycoprotein, and second that the lack of respiratory depression produced by loperamide, which allows it to be safely used therapeutically, can be reversed by a drug causing P-glycoprotein inhibition, resulting in serious toxic and abuse potential."
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11014404&query_hl=7&itool=pubmed_DocSum



Did it say "serious abuse potential"???

So, where can I buy this P-gp?:D No, for real, they talk not only in this text about drug interactions between P-gp and opioids. So, can one buy this P-gp or is it available in other medications in useful amounts? There is a huge difference between in vitro and in vivo studies. But since they point it out so often, that drug-interactions might occur between opioids and P-gp, one should check this...

Shit that would be great. Getting high on loperamide/immodium!!!


Central analgesic actions of loperamide following transient permeation of the blood brain barrier with Cereport (RMP-7).

The bradykinin analog, Cereport (RMP-7), was designed to increase permeability of the blood brain barrier (BBB). ... Cereport might also be used to increase delivery of pharmacological agents across the normal (i.e., non-tumor) BBB. This was accomplished by testing the ability of Cereport to enhance delivery of the peripherally acting opiate agonist, loperamide, to the brain ... Intravenous administration of a combination of Cereport and loperamide produced a significant analgesic effect (2-fold increase in response times) when animals were tested on a hotplate apparatus. Loperamide alone did not produce analgesia. An analysis of the time course of analgesia revealed a graded onset of analgesia which peaked at 30 min, maintained asymptote at 60 min, and began to diminish by 120 min following Cereport and loperamide administration. Finally, the analgesic effects of combining Cereport and loperamide were completely blocked when animals were pre-treated with the opiate antagonist naloxone, demonstrating that the analgesia was mediated through opiate receptors. Collectively, these results suggest that Cereport was able to increase delivery of loperamide across the BBB, allowing it to gain access to opiate receptors in the CNS to produce a centrally mediated analgesic effect. They therefore provide clear evidence that safe and well-tolerated doses of Cereport can increase permeability of the normal (i.e., non-tumor) BBB. Moreover, they provide the first evidence of a pharmacological effect specifically enabled by controlled (i.e., receptor-mediated) modulation of the BBB. "
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9729419&query_hl=7&itool=pubmed_DocSum

Mokelly
01-31-2006, 08:30 AM
so uhhh, WHERE ON EARTH DO WE GET SOME OF THAT CEREPORT?????!!!!!!!!

bogumil
01-31-2006, 10:11 AM
Yeah, that, or from how I understand it, where do we get quinine? And quinine shouldnt be too difficult, or? Anyone an idea?

Edit: It is called quidine, not quinine, sorry.

exitwound
01-31-2006, 11:47 AM
Anything that inhibits P-glycoprotein sounds like it would work. There must be natural plants/substances that have this action! Get hunting!

bogumil
01-31-2006, 03:59 PM
So we have: quidine (a heart medicamentation I think) and Cereport by now, who definately make it cross the bbb. A good start Id say! Someone should post this into the bee forums.

Yeah, we should google for P-gp-inhibitor, P-glycoprotein inhibitor, inhibits P-glycoprotein and so on ... Dude, that sounds great doesnt it?!

Only thing that sucks it that the bb reads about our bbb tries, too.

Hey exitwound, I found a plant that contains quinidine, the strongest p-gp inhibitor:

1. QuinidineAntiarrhythmicCinchona ledgeriana (http://www.rain-tree.com/quinine.htm)

Family: Rubiaceae
Genus: Cinchona
Species: officinalis, ledgeriana, succirubra, calisaya
Synonyms: Quinaquina officinalis, Quinaquina lancifolia, Quinaquina coccinea
Common names: Quinine bark, quina, quinine, kinakina, China bark, cinchona bark, yellow cinchona, red cinchona, Peruvian bark, Jesuit's bark, quina-quina, calisaya bark, fever tree
Parts Used: Bark, wood

http://www.rain-tree.com/quinine.htm

Edit: here is some stuff I found. Links and so on:

The most powerul inhibitors are, like it seems paroxetine and quinidine.

http://www.biomedcentral.com/1741-7015/2/8/abstract

"Tetrafosmin), des Glukoseumsatzes ([18F]FDG) und der Pgp-Aktivität ([3H]Vinblastin) unter dem Einfluß verschiedener Pgp-Inhibitoren (u.a. Verapamil, Vinblastin,Valinomycin). "
It says: "Several P-gp inhibitors (for example Verapamil, Vinblastin, Valinomycin)"
Link: http://www.fz-rossendorf.de/pls/rois/publications_fwp_1998

"
Richard Kim from Vanderbilt University reviewed the most recent developments in the field of P-gp inhibitors [Abstract S1]. Kim presented results of a study using LY335970, a P-gp inhibitor developed by Lilly. In that study, mice treated with LY335970 experienced a substantial increase in nelfinavir concentrations, more pronounced in the CNS than in the plasma, when compared to controls. In addition, LY335970's inhibitory effect seemed only to target P-gp function, with minimal effect on CYP3A4 activity. This compound also proved to be the most potent P-gp inhibitor when compared to other P-gp inhibitors such as cyclosporin and PIs. A number of other compounds are currently under investigation as potential P-gp inhibitors including oral ketoconazole, and preliminary studies revealed encouraging PK results . "
Link:http://www.hopkins-aids.edu/publications/report/mar01_8.html


"[B]Tariquidar (XR9576) is a potent and effective P-glycoprotein (Pgp) inhibitor that can be administered safely with chemotherapy ..."
Link: http://meeting.jco.org/cgi/content/abstract/23/16_suppl/3093

"Inhibition of P-glycoprotein by newer antidepressants ... we investigated citalopram, fluoxetine, fluvoxamine, paroxetine, reboxetine, sertraline, and venlafaxine and their major metabolites desmethylcitalopram, norfluoxetine, paroxetine-metabolite (paroxetine-M), desmethylsertraline, N-desmethylvenlafaxine, and O-desmethylvenlafaxine for their ability to inhibit Pgp. ... All antidepressants tested except O-desmethylvenlafaxine showed Pgp inhibitory activity with sertraline, desmethylsertraline, and paroxetine being the most potent, comparable to the well known Pgp inhibitor quinidine."
Link: http://jpet.aspetjournals.org/cgi/content/short/jpet.102.046532v1

Paregoric Kid
01-31-2006, 10:47 PM
I drink a lot of tonic water, maybe I'll give it a shot.

Zoops
02-01-2006, 01:58 AM
Yeah, quinidine and quinine are just opposite stereoisomers (enantiomers) of one another. quinidine is more potent on the heart, so it probably is better to try taking just plain old quinine for our purposes. I am positive that if quinidine has the effect of increasing loperamide BBB crossing, then quinine would also do it to some extent too. Just not as potent.

As a matter of fact, one can buy quinine tablets OTC in the U.S. It's one of those behind-the-counter-over-the-counter deals. The tablets are like 300 or 350mg (I can't remember exactly) and they are used for treating nighttime leg cramps.

So, a couple quinine tablets, on top of like 20 immodiums would maybe get you off.

I wouldn't take more than two quinine tablets at a time, because it has some kind of effect on the heart, like slows down the beats or something, and an overdose would not be fun.

The tablets of quinine would provide WAAAAAY more quinine than tonic water.

Anyway, something was said about dehalogenating loperamide. That is interesting, but I doubt that it could be done without some pretty severe reaction conditions. That chlorine atom is firmly attached - not reactive at all. Removing it, I don't think, would have ANY effect on the activity, and certainly would only make it LESS likely to cross the BBB, because halogen-carbon bonds in molecules INCREASE their lipophilicity, as a rule. So, you wouldn't want to screw around with that. That hydroxyl group is what we need to mask or get rid of.

I heard about that stuff called "cereport" a couple of years ago. It is an extremely expensive material, available in small quantities only. I think it can only be administered IV. All these animal experiments with loperamide are done with injections (intraperitoneal - where they just jam a needle into the poor wittle mousie's abdominal cavity and shoot it in there).

What do y'all think about that "teamlifereasearch" websit that MkChil put up yesterday - they sell grams of pure 'lope. The manner in which you have to order it is a little funny, though - the dude wants either CASH or a BLANK MONEY ORDER, with the receipt stub attached (so you can't stop payment on the MO after you get the product, he says). So, you have to MAIL the payment to him before anything happens. What does that sound like to you. I think I'll order a gram of lope. I have to get a mailbox over at the local "UPS store." first, though. I can't e-mail the dude from home either, becaue my wife will fucking divorce my ass if she finds out I am still ordering strange chemicals off of the internet, and I am afraid I'll spook the dude if I sent him an e-mail from my work, because my e-mail address ends in "gov."

hmmmm.

bogumil
02-01-2006, 03:13 AM
edited ... sorry, please delete

Opiyum
04-04-2006, 01:32 PM
Where can you get this loperamide? I could definatly use some in the next oh say ten hours. If I were to dose to the point where it covered the withdrawals would I still be able to go to work? Enlighten me please oh great Illuminati.


I detoxed off of heroin, outpatient, using clonipin, muscle relaxants and tegretol
You mentioned tegretol and Im wondering if I shoud dig up my old leftover prescription. I used it because at age eleven I got the flu bad then started Hallucinatiing in a very very bad way. These hallucinations were far more intense than any "hallucinagen" Ive taken. Frightening horrific, complete loss of control of what I was seeing and I was aware of it at the time....I still to this day have never been more scared in my life.
So after a visit to the doc he said I had epilepsy but its not the rolling around on the floor kind its something else I cant describe. My mother could do a better job of this because she saw me though it all. Like I said I was 11 and very frightened for days on end.

Anyway I had to take the Tegretol everyday three times a day for about five years and ever since I've been off of it. What is Tegretol? I realize I should know since I was on it but I was so young at the time my mother was the one who really knew what was going on with me. Why does it help with withdrawal? And once again is this Loperamide the stuff found in Immodium AD cause if so I'm on my way to Giant eagle right away.

Thanks

devilsdrug
04-04-2006, 03:56 PM
opi you lazy fuk check out the infinite (almost) posts on in the search jesus as per loperamide and or imodium

Opiyum
04-04-2006, 04:11 PM
Thats what I did bro and it took me here. And then I realized I had to change my options to allow older threads and posts. This one seems to have the most knowledgable on the subject so I stuck with it. Plus Im hoping Jackie can answer my question about tegretol which Im sure isnt posted anywhere in this forums archives.

Devil is this some sort of initiation because I seem to really irritate you more than anyone ever. Theres a few here that hate me but I hate them but you seem cooler than the Fonz

devilsdrug
04-04-2006, 05:24 PM
dude it was always my job to fuk with the youngins in the pen because some tend to yak to much and show their ignorance rather than sit back and take in the knowledge around them , of course this screen is way different than 1 on `1 in the dorm or cell block or yard ,whatever the moral is that almost always they would be really be mad call me asshole bla bla bla, but in the end it would be that i was right but my methods suck oh yeh it doesnt really matter but are you going to change your avatar everyday now and another oh yeh i see someone took pts aways from me again , i think im gonna cry, no i guess ill donate so i can see who the spineless prick is

caesee
04-04-2006, 05:26 PM
Thats what I did bro and it took me here. And then I realized I had to change my options to allow older threads and posts. This one seems to have the most knowledgable on the subject so I stuck with it. Plus Im hoping Jackie can answer my question about tegretol which Im sure isnt posted anywhere in this forums archives.

Devil is this some sort of initiation because I seem to really irritate you more than anyone ever. Theres a few here that hate me but I hate them but you seem cooler than Fonz


hate is such a strong word...

bogumil
04-04-2006, 07:23 PM
There were tests on rats or mice, that showed that loperamide, wehn injected in large amounts, crosses the bbb, in very tiny amounts though.

qinidine is the best accelerator for this from what I know so far. SWIM has ordered it and will report. The stuff is used for heart problems though, so i dont think that SWIM can use lots of quinidine. But they gave test-animals shots of qinidine and loperamide and it crossed the bbb.

btw: loperamide is supposed to be as strong as fentanyl. the only reason it doesnt feel like this is, that it doesnt cross the bbb. so be careful if you open the gates to your brain ... the lopi-army might just march in and rip it to pieces.

Opiyum
04-04-2006, 08:15 PM
Hate is strong huh?

Forum- A place where ideas can be discussed.

Your not the only one who wishes I had control of my thoughts. Or more importantly control over the ones that become words.


dude it was always my job to fuk with the youngins
You do your job well. I bet you run a tight ship with those painters of yours.


are you going to change your avatar everyday now
Nope I found just the one. hehe

Its been good shareing ideas with you Double D. If you really want I'll try to tone it down only out of respect to you though...and the administrators of course.

I still dont even understand what this points power shit is although I did realize that people took them from me. Originally I thought every time I edited a post they took a point, but no, so dont look at me....Its a popularity contest huh..Fuck that.

chemboy7
04-05-2006, 01:31 AM
finally I wonder just what potentially more potent opioids may be synthesized from loperamide? I asked this question in the hive but the post went unanswered, and now the hive doesnt even exist.

Indeed one could take Loperamide and synth up a batch of Lofentenil Oxalate, very potent. I am not going to post the synth here as its long and it would take me hours to find. Janssen Pharmaceuticals holds the patent on it and it should not be hard for you at all to find for yourself, although the synth would be difficult for anyone without a few years of college organic chemistry.... but we are just reading for information purposes anyways so that doesn't really matter.

chemboy7
04-05-2006, 01:45 AM
actually loperamide is related to meperidine not methadone and it might not be a smart idea to mess around with loperamide in the lab unless you know EXACTLY what you are doing because if you don't know EXACTLY what you are doing the risks of contaminating a batch with MPTP is too great. MPTP is related to loperamide and meperidine and chemically induces parkinsonism/parkinson's disease.

Actually, Alexader Shulgin states in his epic "Controlled Substances" that Loperamide HCL is closely related chemically to Methadone, not Meperidine. If one were to look at the chemical structures of Loperamide and Meperidine they would see for themselves that they are not related (even without knowing anything about chemistry its obvious). I also seen somewhere on here where you claimed that Loperamide was not water soluble... This is also incorrect, it is actually water soluble, my current PDR doesn't give solubilties for Loperamide but I have seen it listed in some of the back issue PDRs at my college for anyone that wants to double check.

Mokelly
04-05-2006, 06:38 AM
damn man if devils finds out where you live......... I mean the whole painter thing man? I think you may have pushed a little too hard on that one for your own good, you should have just stfu.........

cronosaegis
05-21-2006, 07:44 PM
I'm basically a cheapass who's now living in an area where kind chemicals are not readily available. So I've been trying to read about increasing the permeability of loperamide, in addition to sourcing other methods of chemical consumption...

I've heard about using quercitin to possibly bypass the BBB, but I thought I'd share some things I'd seen, to see if anyone with genuine chemistry knowledge had any ideas of how to apply them, with other available chemicals...

Interesting bits about biochemicals, from: http://www.mhhe.com/biosci/genbio/life/articles/article4.mhtml

Anyone know of any bradykinn agonists available from the health store ?:p See here for going past the BBB: http://www.ingentaconnect.com/content/ben/cmciema/2002/00000002/00000002/art00003

A synopsis of the patent with some neat info, for the previously mentioned RMP's... http://www.freepatentsonline.com/5268164.html

Too damn bad we don't know of any naturally occurring peptides that are RMP equivalent.

I know none of this is useful, but I enjoyed reading it and researching the processes- despite not being chemistry literate. Hey, hope springs eternal. Maybe an Opiophile will discover some beautiful RMP growing in our backyards or at the healthfood store.

Se bien, no ?

jacky
05-24-2006, 03:33 AM
took quercitin and loperamide together....a few times.....20 milligrams lop. to a few grams quercitin.....so real effect discernible........maybe the next day from the loperamide I was a little sleepier though.

keep thinking man, you are on the right track.

recently a certian purveyor told me he had sold out of his picralima nitida alkaloids...which is a plant from africa that contains alkaloids with opioid activity, kappa and mu agonist about the potency of pentazocine..these alkaloids have been described as mild like iboga stimulant as well by one chemist in personal communications....this has got me wondering...who is ordering, and what are the effects...I have taken the stuff a few times...but not in doses high enough to do much besided a little dizziness, and obvious stimulant qualitys. I know of a few places that have the material in stock. PM me if anyone is int.

storm
06-04-2006, 04:19 AM
I'm definately interested in this -- have read that quinadine helps to cross the BBB but I don't know where to obtain -- just like cereport. Any ideas?

Zoops
06-12-2006, 05:36 PM
Hey man, I finally got the pyridine needed as the catalyst for the acetylation reaction (yeah, still thinkin' about that - been gone a while - apparently, things have gotten on to bigger and better and even more interesting topics!).

So, the other day, I took 10 loperamide 2mg tabs, crunched them up, dissolved them in about 10ml acetic anhydride, and put about 10 drops of 3-methylpyridine (catalyst - the literature calls for pyridine, but I used 3-methyl pyridine b/c it's what I could get). Cooked the reaction mixture for about 30 minutes at around 190dg F (my oven has degrees F, sorry, I'm not very scientific!)

well, the shit is drying out now. It's light blue/green from the loperamide tablets. We'll see...

I think I really got 100% acetylation this time, because I did what the literature says. acetic anhydride and pyridine is what you need to acetylate a tertiary alcholic hydroxy group.

I will insufflate about half of the shit (should be around 10mg, give or take a few) and see what happens. I am on bupe, but I'll go off of it for about 24 hours before doing it. Keep ya posted.

chemboy7
06-12-2006, 06:14 PM
Hey man, I finally got the pyridine needed as the catalyst for the acetylation reaction (yeah, still thinkin' about that - been gone a while - apparently, things have gotten on to bigger and better and even more interesting topics!).

So, the other day, I took 10 loperamide 2mg tabs, crunched them up, dissolved them in about 10ml acetic anhydride, and put about 10 drops of 3-methylpyridine (catalyst - the literature calls for pyridine, but I used 3-methyl pyridine b/c it's what I could get). Cooked the reaction mixture for about 30 minutes at around 190dg F (my oven has degrees F, sorry, I'm not very scientific!)

well, the shit is drying out now. It's light blue/green from the loperamide tablets. We'll see...

I think I really got 100% acetylation this time, because I did what the literature says. acetic anhydride and pyridine is what you need to acetylate a tertiary alcholic hydroxy group.

I will insufflate about half of the shit (should be around 10mg, give or take a few) and see what happens. I am on bupe, but I'll go off of it for about 24 hours before doing it. Keep ya posted.

Ha, I was just wondering the other day if you had ever gotten around to trying this out... sounds very interesting to me, O-Acetyl Loperamide.

chemboy7
06-12-2006, 08:05 PM
One side note though Zoop; and I don't mean to correct/question your method... mainly because I know that you are much more knoweledgable (sp) in this area than I (in fact I consider the path I walk to be on track with the road you have taken... your like an older version of myself), but it might not be a bad idea to start with miniscule dosages and work your way up gradually factoring in tolerance along the way... because I know that alot of the Phenylpiperidine Opioid Agonist ( to which this chemical beauty would belong) are fully active at less than a mg... not all, but some; and I would hate to see you OD. I believe that you had mentioned that there was no pharmalogical information on this chemical, just patent/synthesis data. It might just be worth the extra chemicals and lengthy wait for results in the name of saftey/science. Either way Zoop, I am more than alittle bit interested in your results. I mean, Acetylation has proven to be effective in administering higher brain plasma concentrations with other drugs... although all the ones I am thinking of were active without the addition of an Acetyl group. I don't know though, you may just come up with a face slapper, and with the ease of synthesis and semi-availability of necessary chemicals you may be on to something major... do keep us posted. :D

LegalizeOpiates
07-01-2006, 02:09 AM
fuck taking diarrea medicine to get high. if it was possible to get high off immodium it would be illeagle like all the other good drugs. c'mon guys just go buy some fuckin real drugs and stop waisting your time. It ain't gonna work.

karmacoma
07-01-2006, 02:32 AM
fuck taking diarrea medicine to get high. if it was possible to get high off immodium it would be illeagle like all the other good drugs. c'mon guys just go buy some fuckin real drugs and stop waisting your time. It ain't gonna work.


man, don't be so negative. are you going through wd?

just because it's legal doesn't mean there's no potential. kratom is legal. you can get poppy seeds at the local health store, can't you? even pods (which is definitely on the 'good' list) can be bought and sold with relative safety. the very fact that it is legal makes it a perfect candidate. and if you end up being right, and it is a blind alley (which is not at all a sure thing) it doesn't hurt to try. and if you don't want to experiment, well please don't discourage these generous souls who do work which we all, some fine day, may benefit from. do i hear music?

SirDonkeyPunch
07-03-2006, 11:20 AM
i found a chemical supply company that sells quinidine hydrochloride and quinidine sulfate, they go for about 30-50$ / 10grams. Considering that experiment above called for 600mg quinidine along with 16 of immodium, thats like 20 doses give/take. they also sell amounts of quinine, if anyone needs some assistance lemme know.

SirDonkeyPunch
07-03-2006, 12:35 PM
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9098875&dopt=Abstract

this makes for some good reading as well, lets find some polysorbate 80

PURPOSE: The possibility of using polysorbate 80-coated nanoparticles for the delivery of the water insoluble opioid agonist loperamide across the blood-brain barrier was investigated. The analgesic effect after i.v. injection of the preparations was used to indicate drug transport through this barrier. METHODS: Loperamide was incorporated into PBCA nanoparticles. Drug-containing nanoparticles were coated with polysorbate 80 and injected intravenously into mice. Analgesia was then measured by the tail-flick test. RESULTS: Intravenous injection of the particulate formulation resulted in a long and significant analgesic effect. A polysorbate 80 loperamide solution induced a much less pronounced and very short analgesia. Uncoated nanoparticles loaded with loperamide were unable to produce analgesia. CONCLUSIONS: Polysorbate 80-coated PBCA nanoparticles loaded with loperamide enabled the transport of loperamide to the brain.

this could be another avenue of interest to those of you doing experimentation

by the way, ive found a source for pure loperamide hcl and quinidine/quinine

Powdered Love
07-05-2006, 06:47 PM
Okay, time to take this loperamide debate in a new direction. I was browsing wikipedia the other day looking at chemical sweeteners and their effects on the body when i stumbled across this little gem:

__________________________________________________ ___________________________________
Mannitol or hexan-1,2,3,4,5,6-hexol (C6H8(OH)6) is an osmotic (http://en.wikipedia.org/wiki/Osmosis) diuretic (http://en.wikipedia.org/wiki/Diuretic) agent and a weak renal (http://en.wikipedia.org/wiki/Kidney) vasodilator (http://en.wikipedia.org/wiki/Vasodilator). It is a sorbitol (http://en.wikipedia.org/wiki/Sorbitol) isomer (http://en.wikipedia.org/wiki/Isomer).
[edit (http://en.wikipedia.org/w/index.php?title=Mannitol&action=edit&section=1)]
[/URL]
Chemical properties

Chemically, mannitol is an alcohol (http://forum.opiophile.org/) and a sugar (http://en.wikipedia.org/wiki/Sugar), or a polyol (http://en.wikipedia.org/wiki/Polyol); it is similar to xylitol (http://en.wikipedia.org/wiki/Xylitol) or sorbitol (http://en.wikipedia.org/wiki/Sorbitol). However, mannitol has a tendency to lose a hydrogen (http://en.wikipedia.org/wiki/Hydrogen) ion (http://en.wikipedia.org/wiki/Ion) in aqueous solutions, which causes the solution to become acidic (http://en.wikipedia.org/wiki/Acid). For this reason, it is not uncommon to add a substance to adjust its pH (http://en.wikipedia.org/wiki/PH), such as sodium bicarbonate (http://en.wikipedia.org/wiki/Sodium_bicarbonate).
[edit (http://en.wikipedia.org/w/index.php?title=Mannitol&action=edit&section=2)]
Mannitol can also be used to open the [U]blood-brain barrier (http://en.wikipedia.org/wiki/Blood-brain_barrier) by temporarily shrinking the tightly coupled endothelial cells (http://en.wikipedia.org/wiki/Endothelial_cell) that make up the barrier. This makes mannitol indispensable for delivering various drugs directly to the brain (http://en.wikipedia.org/wiki/Brain) (e.g. in the treatment of Alzheimer's disease (http://en.wikipedia.org/wiki/Alzheimer%27s_disease)).

Mannitol is also used as a sweetener (http://en.wikipedia.org/wiki/Sweetener) for people with diabetes (http://en.wikipedia.org/wiki/Diabetes). Since mannitol has a negative heat of solution, it is used as a sweetener in "breath-freshening" candies, the cooling effect adding to the fresh feel. In doses larger than 20g, mannitol acts as a laxative (http://en.wikipedia.org/wiki/Laxative), and is sometimes sold as a laxative for children.

It is sometimes used as an adulterant (http://en.wikipedia.org/wiki/Adulterant) for heroin (http://en.wikipedia.org/wiki/Heroin), methamphetamines (http://en.wikipedia.org/wiki/Methamphetamine) or other illicit drugs (http://en.wikipedia.org/wiki/Illicit_drug).

__________________________________________________ ___________________________________


Hmmm.... this got me thinking. Maybe we have been looking in the wrong direction this whole time. I'm sure, because of it being a sweetener, Mannitol is readily available. But even if it is readily available, would it work with loperamide? It's pretty obvious that much more research is needed. If Mannitol were shown to get loperamide across the BBB, I would be the first one buying crates of Immodium, because you can be sure it would not be OTC for long. Anyway... I think someone with more knowledge about Mannitol and how it works on the BBB should look into this because it may just be the key to the OTC high we've all been searching for. :D

WarmCyanide
07-05-2006, 08:24 PM
My only experience working with Mannitol is for the reduction of acute rise intraocular pressure (pressure within the eye), Intracranial pressure and swelling of the trachea. I spilled some on the floor a couple of years ago. It's only about two bucks for 100mL from medical suppliers. The parts that I didnt clean up crystallized almost immediately. Don't even think about using that stuff IV unless it is warmed up thoroughly, feed through a micron filter, cotton or whatever.. you get the idea. I believe it's main mode of action is changing the osmotic gradient of tissues and body fluids. Same reason why it's used as a laxative i'll bet. As for Loperamide, the mechanism of action that i'm aware of it decreases gastric motility or movement, allow the colon to absorb more water from your shit. (is this why opiates can cause constipation???) viola! diarrhea worries magically whisked away. Maybe just stick to banana peels, wing of bat, or eye of newt? ;)

storm
07-22-2006, 11:36 PM
Just a quick update. My wife takes hydroxychloroquine, which is a derivitive of quinine. I tried 600 mgs with 40 mgs of loperamide and nothing. I guess you have to have quinidine for it to work.

insanesteveo
07-23-2006, 01:02 PM
so zoop, what happened with your reaction? did you try out the products?

also, whats the deal with snorting loperamide tabs? anyone have good evidence that works? im staring at 12 - 2mg tabs now. ive never snorted anything, but if it works in the least, ill try it.

Liptonbuddy
08-07-2006, 11:32 AM
I was just wondering if Loperamide actually would make you fail a drug test for opiates? I know eating poppy seeds in excess could cause you to fail, and was just wondering if high doses of Loperamide can do the same? I've read that Loperamide is technically an opiate, so this kind of intrigues me. Thanks a bunch!

candy
08-07-2006, 02:13 PM
To be honest, I really don't know. I am going to say NO, but I could be wrong.

Is this question just purely out of curiosity or are worried about passing a drug test?
I would imagine that someone here must know the answer to that. Keep checking back here to see if someone knows the answer to your question.

Sorry, I couldn't be more help.

Liptonbuddy
08-08-2006, 12:23 AM
The reason I ask is because my work is just starting a drug screening program where they need 2 people a month to take a test. Now, I'll be fine as long as I don't get it this month. I'm currently in the process of weening myself off the drugs that have hindered my life daily for 7 months now. I'm down to 1 vicodin every 6-8 hours or so, but that's still enough to fail a drug test. I was just wondering if I could actually pass it off as just being on a high dosage of Loperamide, since I do have chronic diahrrea when not taking opiates. Serves me right for being dumb enough to drink heavily creamed coffee all day when I'm lactose intolerant. heh It would just be easier to do that, then do the whole "have a clean friend piss in something, then tape it between your leg and balls" trick all of my friends seem to do. I just don't want to get fired since I really love this job, and it would be a shame to get fired for not even being high anymore. Not to mention the fact they do nothing about the 2 staff members who come in drunk almost every day they work. Then again, alcohol is legal, so it must be alright. :rolleyes:

Opiyum
08-08-2006, 12:59 AM
That's a real good question. I would think that you would hear of that happening to people. i never have but it could be a possibilty. Maybe you wont fail when you take a standard dose like normal people but a higher dose may show up.
Hope someone can answer this. It would be good to know.

Good job Lbuddy

zombiewoof23
08-08-2006, 01:47 AM
It would be worth using a home test kit to find out, instead of having to explain it to your employers. And then also report back. That is an interesting question.

Opiyum
08-08-2006, 02:46 AM
Granted Im not the best when it comes to finding info on the net but from what i can tell noone knows the answer to this question. Ophile.org may be the first to find the answer if you do the experiament. you just gotta manke sure that you have no other opiates in your system. Which i guess is pretty obvious. Anyway I hope that someone can try this.
I guess I could when I go back on my suboxone later in the week.
I know the subs wont show in the test but they may interact with the Loperimide so i dont know how conclusive it would be if i tried it while on Subs.

Opiyum
08-08-2006, 08:25 PM
While at the pharmasist today picking up my Subs and newly prescribed Temazepam Iasked if this was possible. The pharmasist said that it was very possible.
I didnt realize till afterwards that I was wearing my Opiophile.org T-shirt. I felt proud and a little stupid upon realizing this.

Hammilton
08-09-2006, 11:52 AM
Depends what the test is for exactly. Most employers just do a dip test with the 5 tests in the standard NIDA battery. If thats what they do you'll be fine even with hydro since the only opiate on that test is morphine. Loperamide is chemically a lot different than morphine so it won't show on that test. I don't know of any that it might. Its my understanding that loperamide is in the piperine-opiate family like meperidine and its cogeners. So maybe for those. i dunno

WarmCyanide
08-09-2006, 01:22 PM
Positive test for anti-diarrheal medication :uhhohh:RPh is hitting the smackk??

chemboy7
08-09-2006, 02:02 PM
What kind of drug test are you talking about? 5 panel? If they do a 5 panel and you show up dirty most places will send your sample to the lab and have it GC/MS'ed which would tell them the specific substance that caused the possitive result... this way they cover all their bases. If they don't send it into the lab all you have to do is complain, people that don't do drugs and test possitive are known to get defensive and aggrivated, and offer to pay for the labwork to prove your clean. If Loperamide was the only Opaite that you have in your system it should be straight.

Zoops
08-17-2006, 07:33 PM
I prolly should wrap this one up. I took the little blue-green ball of putty I recovered from the mixture of loperamide tablets, acetic anhydride and pyridine, mixed it with boiling water, and steep it for about 10 minutes. Then I mixed it with some chai tea hot beverage mix (left over from my 10 month long kratom binge last year. If you wanna make kratom taste good, use Harris Teeter brand chai tea powder). drank it. Had a slight medicinal taste, still smelled slightly of pyrdine. My work-up is not very sophisticated to say the least. More like cave man technology.

I had only gone about 12 hours without bupe. Just can't bring myself to actually go off it for two or three days. Man, I'd be sick! But I guess I'd know I could get well really quick if the acetylated loperamide stuff didn't do anything. But, as I said, I took it. This was about a month ago - I think I pm'd someone about it, but never posted anything? Or did I?

Well, no effects that I could tell, but that definitely doesn't mean it ain't active. My feeling is that if it is, it's not a super-potent one on the level of fentanyl or anything, maybe more like demerol - were you'd need at least 100mg, preferably more to get off. I had only 20mg of this stuff, assuming 100% conversion (and recovery). I prolly ended up with taking 10mg in that mug, after it's all said and done, and on top of bupe about 12 hours earlier, I didn't feel anything. This is definitely not over. I think the real deal is to get some pure loperamide powder and then do the reaction.

If anyone's got the $, you can buy lopermide from this place called 'team life sciences' or something, they're on the web, just yahoo or google it. They only take money orders through the mail, you have to send 'em a blank money order and then trust them to send you your chems. I wasn't really too eager to take that riske, although I did correspond with the dude who works there by e-mail. He was interested in my job that I did for a living, so we talked back and forth about it for a while. I think they're reputable, but not sure.

"sciencelab.com" supposedly sell 5grams of loperamide for like 75 bucks, but it's always on "backorder" tried to order that from them last year. They don't give you any trouble, they just can't get the stuff.

oh well, I will keep my eyes and ears open. Get to work you freaks, grow a pair and buy some friggin acetic anhydride from sciencelab.com - they're the only outfit I know of that'll sell it with no questions asked. It's cheap too. No dea guys are going to come to your house for a 120ml bottle of acetic anhdyride. just say it's for an experiment making esters for high school. DEA has bigger fish to fry than some dude with a four ounce bottle of acetic anhydride.

warmgun
11-02-2006, 09:12 AM
hi,
as a means for curbing symptoms i took to loperamide.
100mg not only took complete care of any symptoms whatsoever and i had undeniable
slight opioid-like effects.

now i don't take any conventional opioids anymore but just lp.
i what to stop completely rather soon though it seems easier than
usual i still cling to the slight positive effects is occasionally get with lp.

i should have known of its powers sooner than i'd never had to suffer w/d.

what are ur exp with lp?

SpecialGuy69
11-02-2006, 09:33 AM
Warmgun- do you think lp's effects would only be noticable to someone with a low tolerance? Do you think that the higher dosage necessary for a higher-tolerance user would have any toxic or negative side effects?

I'm very interested, it would be really nice to be able to just go to the CVS and get something w/no script to cure w/d's!

warmgun
11-02-2006, 09:45 AM
well i haven't heard of such a thing.
to be honest: what interests me even more is what a person with no/very little tolerance would feel.

and if one gets too constipitated there's always a huge amount of VitC which will turn you into a fluid man very fast ;)

i have no idea how safe such an attempt would be.
though beside this constipiation issue which should be treatable suffieciently armed, i am not aware of other dangers beside the usual things to be considered with any opioid.

Levity
11-02-2006, 10:28 AM
Loperamide shouldn't produce any euphoric effects. It can't cross the blood-brain barrier and only effects mu-receptors in the colonic tract.

If you felt something from it, either your brain is in your ass or it was placebo effect. But hey, if it gets you high, it gets you high. Some one chop me up a line of Pepto.

Opiyum
11-02-2006, 02:19 PM
^^^^yeah thats definately what I thought. I used it once or twice and it was only to mute the effects of WD's. It worked rather well and I was suprised.Haven't been in a position to need it for awhile now but to here that someone is using it recreationally and it's doing something for them is great. Way to buck the system man.
I just wish I had a tolerance that would allow that.

nick
11-02-2006, 02:40 PM
Might have confused getting well,with "getting well".Whatever as long as you felt good.

vaxn8
11-02-2006, 03:01 PM
It doesn't cross the bbb in amounts significant enough to get an effect. Now that's true for the recommended human dose range. It is an extremely tiny amount that is able to make it across. When you get up to 25 times the recommended dose, I have no idea how much would cross, and I doubt anyone has even looked at dosages like that to find out.

http://forum.opiophile.org/images/icons/icon4.gifSeriously, taking it in amounts like that, especially more than once is asking for an impaction! You will cause some serious colon problems and will most likely end up having someone dig in your ass to straighten it all out.http://forum.opiophile.org/images/icons/icon4.gif

The only way to get central effects with loperamide is to work with the bbb permeability raising compounds. And I am in NO way recommending that or suggesting it is a good idea. I actually think it is a horrible idea, you do not want random things crossing into your brain- well I don't want random things in my brain.


If you're getting some kind of placebo or location reaction I really think it is a dangerous way to do it. Obviously its up to you, just be careful. Fecal impaction is supposed to be quite painful and it is not a pleasant experience to have it taken care of (at least it doesn't sound fun in my opinion!) of course YMMV.

Levity
11-02-2006, 03:38 PM
It doesn't cross the bbb in amounts significant enough to get an effect. Now that's true for the recommended human dose range. It is an extremely tiny amount that is able to make it across. When you get up to 25 times the recommended dose, I have no idea how much would cross, and I doubt anyone has even looked at dosages like that to find out.

http://forum.opiophile.org/images/icons/icon4.gifSeriously, taking it in amounts like that, especially more than once is asking for an impaction! You will cause some serious colon problems and will most likely end up having someone dig in your ass to straighten it all out.http://forum.opiophile.org/images/icons/icon4.gif

The only way to get central effects with loperamide is to work with the bbb permeability raising compounds. And I am in NO way recommending that or suggesting it is a good idea. I actually think it is a horrible idea, you do not want random things crossing into your brain- well I don't want random things in my brain.


If you're getting some kind of placebo or location reaction I really think it is a dangerous way to do it. Obviously its up to you, just be careful. Fecal impaction is supposed to be quite painful and it is not a pleasant experience to have it taken care of (at least it doesn't sound fun in my opinion!) of course YMMV.


My thoughts exactly.
I had a fecal impaction after my accident. Nothing like being doubly anally fisted while a third hand pulls rock hard shit from your ass.

Long story short, just use fucking heroin.

Sitar
11-02-2006, 06:39 PM
Why would Loperamide be any more constipating than any other opiate? I mean, you're either constipated or you're not. And actually Loperamide is one of the many natural alkaloids present in opium.

In any case, it would probably be a good idea to use a stool softener and/or laxatives with the Loperamide.

I have heard from several different sources that high doses of Loperamide does work to help combat opiate withdrawal. It surely wouldn't hurt to give it a try.

warmgun
11-03-2006, 06:57 AM
And actually Loperamide is one of the many natural alkaloids present in opium.

is that true?
i always thought of it as being a 100% synthetic.

ZodiacKiller
11-03-2006, 07:12 AM
I can't post a source to back this up, but I remember reading a while back that when Loperamide was being developed (at first, it was thought that it would be another powerful analgesic opioid), one in a hundred people tested reported significant opioid effects.

Maybe you're the one in a hundred lucky ones, warmgun. Wouldn't it be nice to walk into Walgreens and get high as fuck for $2.99....


ZK

flipside
11-03-2006, 10:21 AM
I think your thinking of Lomotil ZK, I believe if memory serves ( and that's iffy) it's an RX of atropine w/ codiene, OTC loperamide has no opiates in it, although there have been studies that at extremely high doses delerium has been reported

Narkotikon
11-03-2006, 10:40 AM
Warmgun- do you think lp's effects would only be noticable to someone with a low tolerance? Do you think that the higher dosage necessary for a higher-tolerance user would have any toxic or negative side effects?

I'm very interested, it would be really nice to be able to just go to the CVS and get something w/no script to cure w/d's!


I've taken loperamide several times, and I can't say that it really does much for me. I mean, I think the highest does was 40 milligrams or something like that. I can't imagine taking 100. I just don't see it helping much because it doesn't cross the BBB. It does help with GI problems, but that's about it. I think it must be a placebo effect if it helps with anything else. If you were really desperate and had GI problems, I'd just go to the doctor and get a script for Lomotil. At least that will provide some relief for other things. But it has atropine in it, so it's probably not a good idea to take too much. Yeah, I wish we lived in the days when you could order heroin through the Sears catalog.

flipside
11-03-2006, 10:43 AM
Yeah, damn prohibitionist, afraid all those Chinese opium smoking men were gonna lure their "white" women into their opim dens and rape em. LOL

Narkotikon
11-03-2006, 10:51 AM
Yeah, damn prohibitionist, afraid all those Chinese opium smoking men were gonna lure their "white" women into their opim dens and rape em. LOL

Yeah, tell me about it. Narcotics are outlawed because the Chinese are sexual predators. Cocaine because white "masters" were afraid that their african-american workers would revolt, even though they were given it to increase productivity. Why was weed banned? I don't remember. Something to do with the southern states I think. Or maybe that's just for the cocaine. It's all just a bunch of pseudo-moral bullshit.

suffocate
11-03-2006, 02:37 PM
Reading through this post again, I found a point that requires a bit of clarification. The dosage mentioned was 100mg's. Now, the recomended dosage for loperamide is 2mg, plus an additional 1mg after each loose bowel movement (to a maximum of 4mg per 24-hour period). This would mean that you took a 50 dosage units at once.

Perhaps this was why you felt opiate-like effects, seeing as how you took such a mega-dose. Perhaps also you were mislead in regards to the actual dosage you took (just a though, try not to take it the wrong way).
I think it needs to be stressed to anyone without much experience in these matters that 100mg can cause overdose resulting in: "Symptoms of a loperamide overdose may include headache; nausea; vomiting; dry mouth; dizziness; drowsiness; or confusion." (Quoted from Yahoo! Health). Such as large dose of loperamide may also cause severe constipation ultimately resulting in fecal impaction, a serious medical condition that often requires surgical removal of the impaction, as well as [often] the removal of part of the large intestine.

I personally use loperamide for withdrawl symptoms, but usually in the dosage area of 4mg to start, as well as 2mg additionally every 3 or 4 hours, only if cramping or loose stool persist.

I though that this was an important point to bring up, seeing as how the dosage mentioned was so incredibly high. Perhaps someone else can comment on this (warmgun?).

madnesscult
11-03-2006, 02:55 PM
Yeah, tell me about it. Narcotics are outlawed because the Chinese are sexual predators. Cocaine because white "masters" were afraid that their african-american workers would revolt, even though they were given it to increase productivity. Why was weed banned? I don't remember. Something to do with the southern states I think. Or maybe that's just for the cocaine. It's all just a bunch of pseudo-moral bullshit.

This is what I posted in the "Dog Food" thread...

"On the subject of opiates for coughs...

Apparently morphine and heroin were first marketed as cough remedies (TB and others being bid scourges at the time), so mothers would give the shit to their colicy babies and stuff. The history channel just started airing a series called "Hooked: Illegal Drugs and How They Got That Way". Apparently heroin was outlawed because of the Chinese immigrants in the country around the turn of the century, with all of them opium dens and stuff. I guess there were a bunch of rumors that the Chinese guys were getting white women high and having sex with them...so the whole outlawing of opiates came from a fear of white women being seduced, same reason cocaine was outlawed - it was said that when black men used coke, they would get uncontrollable sexual urges and go after the white girls. I guess another reason opiates were outlawed was that it had pretty much ruined China at that point...there were so many junkies that no one was really working. It's a really neat series.

I have also heard (I don't remember where) that heroin was developed as a cure for morphine addiction, although I doubt that."

Narkotikon
11-03-2006, 03:22 PM
This is what I posted in the "Dog Food" thread...

"On the subject of opiates for coughs...

Apparently morphine and heroin were first marketed as cough remedies (TB and others being bid scourges at the time), so mothers would give the shit to their colicy babies and stuff. The history channel just started airing a series called "Hooked: Illegal Drugs and How They Got That Way". Apparently heroin was outlawed because of the Chinese immigrants in the country around the turn of the century, with all of them opium dens and stuff. I guess there were a bunch of rumors that the Chinese guys were getting white women high and having sex with them...so the whole outlawing of opiates came from a fear of white women being seduced, same reason cocaine was outlawed - it was said that when black men used coke, they would get uncontrollable sexual urges and go after the white girls. I guess another reason opiates were outlawed was that it had pretty much ruined China at that point...there were so many junkies that no one was really working. It's a really neat series.

I have also heard (I don't remember where) that heroin was developed as a cure for morphine addiction, although I doubt that."

You're right, heroin was initially marketed as a non-addictive cure for morphine addiction by Bayer, but they dropped it when they found out that heroin is metabolized into morphine and is more addictive because of the increased lipid solubility. It was also in "soothing syrups" for collicy babies and other patent medicines. Just like cocaine was in infant teething drops. That's how I found out about this stuff, those History Channel shows. They were really interesting. Yeah, the chinesse emperor had tried to outlaw opium in China during the 19th century, but it was such a profitable commodity for the European superpowers of the day, they engaged in the Opium Wars, which opened up China for trade with the West. That's why Hong Kong was a British dominion until 1998. I think it was 1998 when they formally handed it back to the Chinesse. Of course opium had been used in China before westerners came, but it was taken orally. The Portugesse introduced smoking opium with tobacco in the sixteenth century I think.

ZodiacKiller
11-03-2006, 04:50 PM
I think your thinking of Lomotil ZK, I believe if memory serves ( and that's iffy) it's an RX of atropine w/ codiene, OTC loperamide has no opiates in it, although there have been studies that at extremely high doses delerium has been reported

Nope, I'm talking about Loperamide (aka. Immodium). It's long been known as a "junky trick" for its withdrawal-stopping ability. And also has been referred to as "over the counter methadone" in some articles and discussions on it. There has been threads here discussing it many times.

Again, I can't source this, but I remember reading that it shares a similar molecular structure with one of the opioids, and was initially developed as another marketable opiate, but when it's inability to cross the BBB was discovered, it was relegated to an uncontrolled substance for it's diahhrea controlling property. And that is one of the properties of opiates (constipation), so it sounds like a possiblity to me.

But I ain't no scientist, so I could be wrong....


ZK

flipside
11-07-2006, 08:25 AM
This is what I posted in the "Dog Food" thread...

"On the subject of opiates for coughs...

Apparently morphine and heroin were first marketed as cough remedies (TB and others being bid scourges at the time), so mothers would give the shit to their colicy babies and stuff. The history channel just started airing a series called "Hooked: Illegal Drugs and How They Got That Way". Apparently heroin was outlawed because of the Chinese immigrants in the country around the turn of the century, with all of them opium dens and stuff. I guess there were a bunch of rumors that the Chinese guys were getting white women high and having sex with them...so the whole outlawing of opiates came from a fear of white women being seduced, same reason cocaine was outlawed - it was said that when black men used coke, they would get uncontrollable sexual urges and go after the white girls. I guess another reason opiates were outlawed was that it had pretty much ruined China at that point...there were so many junkies that no one was really working. It's a really neat series.

I have also heard (I don't remember where) that heroin was developed as a cure for morphine addiction, although I doubt that."

Heroin was actually prescribed as a cure for alcoholism believing that while drunk men beat their wives, got in street brawls, the H user was less of a nusiance to socoety. I have a old pic of a woman by a water fountain in the couthouse shooting up in the hallway. It's crazy.

As for China their society had indeed been ravaged by o abuse and they refuesed to export to England anymore so England declared war onChina. The US got thier supply but it still remained illegal in China.

flipside
11-07-2006, 08:27 AM
Nope, I'm talking about Loperamide (aka. Immodium). It's long been known as a "junky trick" for its withdrawal-stopping ability. And also has been referred to as "over the counter methadone" in some articles and discussions on it. There has been threads here discussing it many times.

Again, I can't source this, but I remember reading that it shares a similar molecular structure with one of the opioids, and was initially developed as another marketable opiate, but when it's inability to cross the BBB was discovered, it was relegated to an uncontrolled substance for it's diahhrea controlling property. And that is one of the properties of opiates (constipation), so it sounds like a possiblity to me.

But I ain't no scientist, so I could be wrong....


ZK

Like I said "if memory serves "( and that's iffy) Hope grampa is still doing better.

stross
11-15-2006, 01:54 PM
Not sure if anyone said this already...but: Loperamide was actually a Schedule V substance when it first started being used because of its ability to cause "opiate-like withdrawal symptoms." Long-term users of the drug began complaining of these symptoms upon cessation. Interesting, ehh? It was eventually taken off because it has little-to-no potential for abuse. If you look on the box, it says not to take it for x number of days (which is for multiple reasons, (1) severe constipation which is a danger to the body and (2) physical addiction).

I also found this in the Opiophile.org archives:

Pharm Res 1997 Mar;14(3):325-328 Delivery of loperamide across the blood-brain barrier with polysorbate 80-coated polybutylcyanoacrylate nanoparticles.

Alyautdin RN, Petrov VE, Langer K, Berthold A, Kharkevich DA, Kreuter J

Department of Pharmacology, Sechenov Medical Academy, Moscow, Russia.

PURPOSE: The possibility of using polysorbate 80-coated nanoparticles for the delivery of the water insoluble opioid agonist loperamide across the blood-brain barrier was investigated. The analgesic effect after i.v. injection of the preparations was used to indicate drug transport through this barrier. METHODS: Loperamide was incorporated into PBCA nanoparticles. Drug-containing nanoparticles were coated with polysorbate 80 and injected intravenously into mice. Analgesia was then measured by the tail-flick test. RESULTS: Intravenous
injection of the particulate formulation resulted in a long and significant analgesic effect. A polysorbate 80 loperamide solution induced a much less pronounced and very short analgesia. Uncoated nanoparticles loaded with loperamide were unable to produce analgesia. CONCLUSIONS: Polysorbate 80-coated PBCA
nanoparti cles loaded with loperamide enabled the transport of loperamide to the brain.

PMID: 9098875, UI: 97253432

Life Sci 1983;33 Suppl 1:315-318 Loperamide: evidence of interaction with mu and delta opioid receptors.

Giagnoni G, Casiraghi L, Senini R, Revel L, Parolaro D, Sala M, Gori E

Loperamide was tested on electrically-evoked contractions using a series of "in vitro" isolated preparations, in comparison with morphine, met-enkephalin, beta-endorphin, ethylketocyclazocine used as representative agonists of mu, delta, epsilon, kappa receptors respectively. The IC50 of loperamide on myenteric
plexus longitudinal muscle of guinea pig ileum was found to be 1.90 X 10(-7)M and equal to that of morphine. The IC50 on mouse vas deferens was found to be 13.02 X 10(-7)M. In this tissue, loperamide resulted as active as morphine, but 54 times less active than met-enkephalin (IC50 0.24 X 10(-7)M). On the rat vas
deferens where, as expected, beta-endorphin was strongly active (IC50 1.38 X 10(-7)M), morphine exerted a stimulatory action within the range 10(-5)M-10(-4)M and loperamide was only poorly depressive. The Ke value of naloxone, a specific mu receptor antagonist, against loperamide in the guinea pig ileum was 3.83 nM, and in the mouse vas deferens was 82.87 nM indicating that
loperamide in the guinea pig ileum acts on mu receptors while in the mouse vas deferens on another opiate receptor.

PMID: 6319884, UI: 84116593

vaxn8
11-15-2006, 02:23 PM
Why would Loperamide be any more constipating than any other opiate? I mean, you're either constipated or you're not. And actually Loperamide is one of the many natural alkaloids present in opium.
In any case, it would probably be a good idea to use a stool softener and/or laxatives with the Loperamide.
I have heard from several different sources that high doses of Loperamide does work to help combat opiate withdrawal. It surely wouldn't hurt to give it a try.

Since none of the drug (or minute amounts) are able to act on the CNS, the whole dose is available to act at peripheral receptors, making the constipating effects seem stronger for the amount used. If you were using morphine to constipate, it would take a much higher equivalent dose since you have lots of the drug going to the brain and only part available to act at peripheral receptors.


is that true?
i always thought of it as being a 100% synthetic.

It is synthetic, it's a demerol analog.


If you were really desperate and had GI problems, I'd just go to the doctor and get a script for Lomotil. At least that will provide some relief for other things. But it has atropine in it, so it's probably not a good idea to take too much.

Lomotil is actually diphenoxylate, which is another demerol analog, but different from loperamide. If you are trying to use for w/drawal, you would NOT want lomotil. Small doses of atropine are okay, and will help reduce cramping, large doses are no fun. If you could get the diphenox on it's own, that would be preferred. It actually has CNS effects at 2-3 times the recommended dose, unfortunately the atropine at that dose is way too much.

Papa Verine
11-15-2006, 03:04 PM
Everybody.

I have A LOT of experience with Loperamide. I researched the hell out of it a couple years ago when I was w/d and learned quite a bit. I experimented a lot with it on myself and came up with some interesting stuff.

First of all, it is an opioid similar to Demerol (meperidine) but it crosses the BBB very poorly. I have personally taken up to 200mg at a time to see if the little bit that does cross would get me feeling the opioid effects. When I say it crosses poorly I mean it. There are very little effects even at such a high dose.

Here's where it gets interesting though. Loperamide is a substrate of P-glycoprotien. P-gp is a transporter that makes up part of the BBB by EFFLUX from the brain. (in simple terms) Drugs that are substrates of p-gp cannot enter because the p-gp flows out of the brain and into the blood. It's like trying to swim up river. Now, certain drugs have been found to be p-gp inhibitors. They can slow down the efflux and potentially let substrates in. If you can completely shut down that efflux Loperamide can enter the brain and produce the desired effects.

Some drugs that are known p-gp inhibitors are quinidine, ketoconazole, retonivir, cyclosprin A and Erythromycin. (in order of potency actually). I have had success with ketoconazole. I would dose up on it taking a double dose and a half hour later I'd take about 40mg of loperamide.

It works. unfortunately the effects are not great because it is still only seeping into the brain. Also, there are side effects to these p-gp inhibitor drugs and side effects to taking too much loperamide. It works but it isn't all that pleasant on the GI system. I'd compare the constipating effects of Loperamide to any other strong opioids though. After a couple days you can pass some tennis balls.

This is something I still do if there's nothing else available. It's a LAST resort.

stross
11-16-2006, 10:20 PM
40mg of loperamide? Wouldn't that constipate the hell out of you?

During withdrawal from a 80-120mg OC habit, 6mg of loperamide stopped the horrible diarrhea I experienced. I can't imagine what 40mg would do, especially with its long half-life. Geez man.

Coddfish
11-17-2006, 11:17 AM
^^^did you miss the 200 mg part of that previous post?

Papa Verine
11-17-2006, 01:51 PM
I was thinking the same thing. I took 200mg at once a couple times. I know what you're thinking but the constipation was no worse than what I get from Heroin or other potent opiates. It's a couple days with no gut motility. The problem is that the high isn't sufficient enough to be worthwhile having to deal with unwanted side effects. It also causes some nausea for hours and I don't get nausea from opiates anymore so that sucks too.

All in all Loperamide isn't worth trying to get high off of. I'm craving opies pretty bad right now and I'm not considering it.

acey
12-04-2006, 02:48 AM
Yeah, tell me about it. Narcotics are outlawed because the Chinese are sexual predators. Cocaine because white "masters" were afraid that their african-american workers would revolt, even though they were given it to increase productivity. Why was weed banned? I don't remember. Something to do with the southern states I think. Or maybe that's just for the cocaine. It's all just a bunch of pseudo-moral bullshit.

first post, hello eh'rybody....first off...Opium was another one of the white brit's tools to control and conquor. You every wonder why China is closed to the western world nowadays? Think about it!

Opium fuct up China for a long while, hence the opium dens, we hear about, thinking oh, those chinese really know how to chill out, be lazy, and take advantage of people. We are mis-informed people.
The white britian people introduced and shipped crates and crates of this stuff into China and it worked for awhile, untill one chinese Emporor realized what was happening, and burnt hundreds of thousands of crates of Opium (I know its a bittersweet thought to imagine all that opium!), having built up an army, and erradicated the "parasite" that had infested and was destroying the nation.

And finally to this day closed the doors to the western world. You dont hear much about opium dens in England.

Just droppin a lil truth.

acey
12-04-2006, 03:09 AM
Everybody.

I have A LOT of experience with Loperamide. I researched the hell out of it a couple years ago when I was w/d and learned quite a bit. I experimented a lot with it on myself and came up with some interesting stuff.

First of all, it is an opioid similar to Demerol (meperidine) but it crosses the BBB very poorly. I have personally taken up to 200mg at a time to see if the little bit that does cross would get me feeling the opioid effects. When I say it crosses poorly I mean it. There are very little effects even at such a high dose.

Here's where it gets interesting though. Loperamide is a substrate of P-glycoprotien. P-gp is a transporter that makes up part of the BBB by EFFLUX from the brain. (in simple terms) Drugs that are substrates of p-gp cannot enter because the p-gp flows out of the brain and into the blood. It's like trying to swim up river. Now, certain drugs have been found to be p-gp inhibitors. They can slow down the efflux and potentially let substrates in. If you can completely shut down that efflux Loperamide can enter the brain and produce the desired effects.

Some drugs that are known p-gp inhibitors are quinidine, ketoconazole, retonivir, cyclosprin A and Erythromycin. (in order of potency actually). I have had success with ketoconazole. I would dose up on it taking a double dose and a half hour later I'd take about 40mg of loperamide.

It works. unfortunately the effects are not great because it is still only seeping into the brain. Also, there are side effects to these p-gp inhibitor drugs and side effects to taking too much loperamide. It works but it isn't all that pleasant on the GI system. I'd compare the constipating effects of Loperamide to any other strong opioids though. After a couple days you can pass some tennis balls.

This is something I still do if there's nothing else available. It's a LAST resort.

quinidine, ketoconazole, retonivir, cyclosprin A and Erythromycin. Are any of these available OTC or at healthfood stores.
Aslo, Orange, grapefruit, lemon, tangerine, basically all citrus products contain p-gp inhibitors and suppliments are either made or being made.....just google "inhibit P-glycoprotien".....

OxyContinuously
12-04-2006, 07:47 AM
Interesting thread and such but I hate to bust everyone's bubble. There is no opiod activity in loperamide, it's not even an opiate. Someone brought up a good point that it doesn't cross the blood brain barrier. I wish it was a narcotic, but then again, there's another pipe dream

suffocate
12-06-2006, 07:51 PM
There is no opiod activity in loperamide, it's not even an opiate. Someone brought up a good point that it doesn't cross the blood brain barrier. I wish it was a narcotic, but then again, there's another pipe dream

You are correct in saying that loperamide is not an opiate, but it is an opioid. Despite the fact that loperamide is not an analgesic and cannot effectively cross the blood brain barrier, it is still classified as a narcotic. Although not a narcotic analgesic, loperamide is considered a narcotic antidiarrheal. Also, while having no (or negligible, depending on who you talk to) opioid activity in the brain or central nervous system, it does demonstrate opioid agonist activity on the mu-opioid receptors in other parts of the body (particularly in the large intestine).

I hope that I did not come across as attempting to undermine your intelligence as that was not, by any means, my goal.

Calling it a pipe dream would be an understatement :D! If someone did however discover how to make loperamide penetrate the BBB, there would likely (more than likely) instantaneously be a worldwide shortage of Immodium and Kaopectate (I can imagine it now... "Now for our top story, millions of westerners have spent the last week in their bathrooms as pharmaceutical companies are battling a 2,000 fold increase in demand for antidiarrheal medicine).

Papa Verine
12-06-2006, 09:18 PM
Interesting thread and such but I hate to bust everyone's bubble. There is no opiod activity in loperamide, it's not even an opiate. Someone brought up a good point that it doesn't cross the blood brain barrier. I wish it was a narcotic, but then again, there's another pipe dream

OK, I wanted to drop the whole "Loperamide" discussion but I guess it must go on and I'm going to continue on with what I learned over the years.

Loperamide CAN be a psychoactive opioid, and infact very easily!
Read my thread above and continue on to this one!

Loperamide does NOT cross the Blood Brain Barrier under normal circumstances in ANY amount.

However,

There are also chemotherapy drugs that do not cross the BBB and therefore will not work to fight off brain tumors. These drugs work well on tumors throughout the body to kill cancerous tumors but have no premeability through the BBB, hence they don't work in the brain. The BIG drug companies who market these drugs have invested HUGE amounts of money into why their drugs don't work on brain tumors. We opiophiles have a thing or two to learn from their studies!!!!!!!

Loperamide is a substrate of P-glycoprotien. (It just so happens to be, lucky us...) P-glycoprotien makes up one small part of the so-called Blood Brain Barrier by Efflux.

This is an important part of what's going on in the BBB. "Efflux" means that in this narrow channel the flow is going in one direction and one direction only. There is no "Influx" at the P-glycoprotien sites. Period!!!! This is why Loperamide will never be a "potent opioid". But listen closely opiophiles... If you can shut down the flow of P-glycoprotien at these sites in the BBB, Loperamide will be able to enter the brain. It's an open door that Loperamide can and will enter but there's no real force behind it. If you ingest a P-glycoprotien inhibitor and follow up with a large dose of Loperamide you will feel the effects of loperamide crossing the BBB and activating mu-opiod receptors. The activation will never be "Heavy" and you will never get a rush or any potent opioid effects. You will get activation by using P-gp inhibitors but the entrance to the brain will never be "uninhibited and resistance free opioid receptor activity".

I've done it and it works. I've taken a P-gp inhibitor and followed up with a large dose of loperamide and I've felt the effects. If you have used Loperamide to help with W/D's than you will recieve considerably better results by inhibiting P-glycoprotien before ingesting loperamide.

Some people may have a natural lack of P-glycoprotien and these people will feel the opioid effects of loperamide much better than the rest of us. The rest of us have to chemically inhibit it with one of the drugs I mentioned in my previous thread.

Papa Verine
12-06-2006, 09:26 PM
Remeber this. I may have said previously that Loperamide isn't worth fucking with but if you have a P-glycoprotien inhibitor, you will feel it! To relieve yourself of W/D's, this is an Excellent tool.

Some known potent P-glycoprotien inhibitors;

Quinidine
Ketokonazole
Retonavir
Cyclosporine A
Erythromycin

robojunkie
12-06-2006, 09:34 PM
Could someone explain this: I know loperamide doesn't cross the BBB without some kind of delivery system, therefore there are no central opiate effects. Yet it can essentially with enough of a dose relieve virtually all withdrawal symptoms, not just the runs and such. Vax? Anyone? I have tried to find this explanation in several articles and have failed. I know it works for WDs only but I just don't get it based on its inability to get to the brain. No WDs equals something acting agonistically at mu-OR.

red26
12-06-2006, 10:16 PM
My thoughts exactly.
I had a fecal impaction after my accident. Nothing like being doubly anally fisted while a third hand pulls rock hard shit from your ass.

Long story short, just use fucking heroin.


Whers poonwalla when you need him? His sister is a nurse and had to pull marble sized pieces of shit outta this junkies ass for a good 45 minuites!!!! The rest of it goes that the junkie went home and told his mom what had happened. She of course flipped out, and made said dude to get her a buncha flowers and bring that shit to her straight away!!!! HA! If I could remember all the sweet, caring nurses that helped me out over the years I'd give em all flowers in a heartbeat. Especially that one that snuck me in a shot of Dilaudid "FOR THE ROAD".

jacky
12-07-2006, 12:11 AM
YOUR A GENIUS PAPA VER!!!

damn, if what your are saying actually works, and I dont doubt you, then you are one of the first people to come up with an alternate way of using lop. that crosses the BBB.

an older opiophile member with chronic pain was taking 200+ milligrams a day in conjunction with their other pain meds. they contacted me as they were worried about withdrawls as they couldnt afford to keep buying the loperamide daily, due to their insurance costs on their standard meds going up. they stated that they felt shitty when they tried to quit.

a few other freinds of mine clued me in a few years ago that they found loperamide helped considerably some effects of opioid withdrawl.

I started taking the drug with dxm, and swear that enhanced weirdness was felt. I also notice a stimulant effect a few hours after taking loperamide, and sedative effects. it says RIGHT on the box that loperamide can have sedative effects. it also seems to be a good mix with standard opiates and nutmeg.

In one study done on seasoned opioid users, 1 out of 10 people experienced euphoria when taking loperamide.
the same study reports that the plasma levels peak at around 30 HOURS after the loperamide is taken. and the drug is mostly out of the system by 72 hours.
there are also metabolites produced when consuming loperamide, and I wonder, if some of these metabolites are more viable candidates for crossing the BBB.
I have a question about the above information, could some psychoactivity from loperamide be felt not the day the materials is consumed, but the next day, when the materials is at its peak in the bloodstream? might some of the metabolites increase its effects?
could drinking your urine 30 hours after taking large amounts of loperamide cause a psychoactive effect?

there are hoards of opioid receptors ALL OVER our bodies....brain cells are found in other parts of the body besides the brain...I think that it is possible that our feelings of wellbeing, and opioid effects, might be beneficially enhanced by opioid receptors BESIDES those that reside in the brain. I personally dont believe the body can be looked at in such a defined way as to seperate the brain and body when it comes to considerations of psychoactives. of course the brain is important for psychoactivity, I just suggest somatic response not be looked at as unimportant in these considerations.

some day a chemist out there with take loperamide, and turn it into.........DOPERAMIDE!!

hovadagod
12-08-2006, 08:06 PM
You people are nuts who total deny the possibility of loperamide crossing the BBB. it def. works for WD's and I've personally been craving like crazy then taken about 10mg and craved less and felt better. Not Opi feeling but no WD's and less cravings. IT works. Try it before citing a bunch of crap;

Papa Verine
12-09-2006, 01:15 PM
quinidine, ketoconazole, retonivir, cyclosprin A and Erythromycin. Are any of these available OTC or at healthfood stores.
Aslo, Orange, grapefruit, lemon, tangerine, basically all citrus products contain p-gp inhibitors and suppliments are either made or being made.....just google "inhibit P-glycoprotien".....

Hey Acey, I've tried to inhibit P-gp with large dosages of Quercetin, which is the active ingredient in citrus products responsible for this action but it just didn't work. I expected it to work but I was disappointed when it didn't. I used oral ketoconazole when I did it because that's the only P-gp inhibitor I had when I discovered the medical studies being done on this. It worked very well and what I got after the combination was a feeling like a low dose of methadone. It lasted for a couple days. It was very noticable with the Ketoconazole/Loperamide combo. Quercetin didn't do anything??? I think this whole process is more complicated then my descriptions are about how it works so the only thing I have to go on here is my personal experience. I also read quite a bit that Clarithromycin was a P-gp inhibitor like Erythromycin but I tried this drug a few times at various dosages and felt nothing. So, the only drug I have personal experience with and can say undoubtably works is Ketoconazole.

jacky
12-09-2006, 01:21 PM
I tried the quercetin combination as well....great anti-oxidant, but it didnt seem to increase any of loperamides effects.

flipside
12-09-2006, 02:14 PM
Seeing as how this could potentially help me out a great deal right now. I am taking the ketaconozole I have and 40mg of loperimide. i will report back in a bit. pap ver if this works for me I will be forever grateful for your time and research in this post!

Powdered Love
12-10-2006, 06:15 AM
alright, i feel like i've gotta post my thoughts on lope because i think others may benefit from what i have to say here...


first of all, i think lope gets a bad wrap... i mean, it really gets beaten down like it methdone's red-headed step child or something... (well, i suppose chemically, it is... but still)

the past three times i've been in the middle of WDs.. i've taken loperamide at doses around 6 to 10mg, and EVERY time i take it, my WD symptoms completely disappear and (much to my surprise :D ) i actually feel *gasp* slight euphoria!

When I say slight, i do really mean slight.. as in, a small lift in mood. Seriously though, Lope has been a GODSEND when i'm in the middle of WDs... It's gotten to the point where I actually carry three Immodium pills with me at all times for emergencies.

I really can't ignore lope's effects on me anymore, that is why i have chosen to post this.. i'm very serious about this.. when i take lope for WDs, ALL of my symptoms go away. Ass-piss, cramps, lethargy, low appetite, depression, aches, pains, etc, etc.... the whole nine yards. I actually feel normal.

I find that it also makes me drowsy at about the 2 hour mark, and i sleep very easily on lope, as opposed to my irregular, insomniac sleep cycles. And another good point, the WDs stay at bay for about 2 days!

If you are reading this and haven't tried loperamide for WD.. i strongly suggest that you take in next time you go CT. I also know that probably not everyone can feel effects from lope, and maybe i am just extremely lucky (or maybe all my previous ecstasy use has left HOLES in my brain for the lope to pass through).. but i thought i would just put it out there.

So, don't drop the lope just yet... it may just prove to save your ass one day like it's done for me three times now.:D

flipside
12-10-2006, 06:34 AM
Papa ver I am eternally grateful!! I took 400mgs of the nitrozole and ended up taking 80mg of the loperimide , all WD symptioms ceased and were still being held at bay this am. Did not notice a great deal of euphoria or anything but it take a hell of a lot of pure pharm grade narcotices to do that for me anymore.... I DID sleep though wich is something I can NEVER do when WD'ing no matter how many bezo's I take. So in short I tried it , it worked. Thank you!! I did take some colace in case of plumbing problems.

Whoever asked if the meds listed to push the lope acrsoss the BBB are OTC no they arre RX'd antibiotics.

Kyuss"" Thanks to you also my dear.. I tried seed tea in desperation because it is all that is availabe to me for the moment ( there goes my spring crop LOL!) Ended up drinking it this am cause I wanted to expericnce ^^ first, this am I am not feeling sick and am a lot happier than I was earlier.:)

Pwdered Love: It certainly did save my ass!! LOL no pun intended.

Papa Verine
12-10-2006, 10:11 AM
alright, i feel like i've gotta post my thoughts on lope because i think others may benefit from what i have to say here...


first of all, i think lope gets a bad wrap... i mean, it really gets beaten down like it methdone's red-headed step child or something... (well, i suppose chemically, it is... but still)

the past three times i've been in the middle of WDs.. i've taken loperamide at doses around 6 to 10mg, and EVERY time i take it, my WD symptoms completely disappear and (much to my surprise :D ) i actually feel *gasp* slight euphoria!

When I say slight, i do really mean slight.. as in, a small lift in mood. Seriously though, Lope has been a GODSEND when i'm in the middle of WDs... It's gotten to the point where I actually carry three Immodium pills with me at all times for emergencies.

I really can't ignore lope's effects on me anymore, that is why i have chosen to post this.. i'm very serious about this.. when i take lope for WDs, ALL of my symptoms go away. Ass-piss, cramps, lethargy, low appetite, depression, aches, pains, etc, etc.... the whole nine yards. I actually feel normal.

I find that it also makes me drowsy at about the 2 hour mark, and i sleep very easily on lope, as opposed to my irregular, insomniac sleep cycles. And another good point, the WDs stay at bay for about 2 days!

If you are reading this and haven't tried loperamide for WD.. i strongly suggest that you take in next time you go CT. I also know that probably not everyone can feel effects from lope, and maybe i am just extremely lucky (or maybe all my previous ecstasy use has left HOLES in my brain for the lope to pass through).. but i thought i would just put it out there.

So, don't drop the lope just yet... it may just prove to save your ass one day like it's done for me three times now.:D

Hey PL, I suspect that you may be one of the lucky people who have a natural defficiency of P-glycoprotein. With the myriad of different things that can go on in the human body I don't see why this wouldn't happen to some people.

Flipside, I'm really glad this helped you. I kept W/D's away like this for a couple days myself!!!! Anything that helps is a valuable tool!!!

flipside
12-10-2006, 11:05 AM
alright, i feel like i've gotta post my thoughts on lope because i think others may benefit from what i have to say here...


first of all, i think lope gets a bad wrap... i mean, it really gets beaten down like it methdone's red-headed step child or something... (well, i suppose chemically, it is... but still)

the past three times i've been in the middle of WDs.. i've taken loperamide at doses around 6 to 10mg, and EVERY time i take it, my WD symptoms completely disappear and (much to my surprise :D ) i actually feel *gasp* slight euphoria!

When I say slight, i do really mean slight.. as in, a small lift in mood. Seriously though, Lope has been a GODSEND when i'm in the middle of WDs... It's gotten to the point where I actually carry three Immodium pills with me at all times for emergencies.

I really can't ignore lope's effects on me anymore, that is why i have chosen to post this.. i'm very serious about this.. when i take lope for WDs, ALL of my symptoms go away. Ass-piss, cramps, lethargy, low appetite, depression, aches, pains, etc, etc.... the whole nine yards. I actually feel normal.

I find that it also makes me drowsy at about the 2 hour mark, and i sleep very easily on lope, as opposed to my irregular, insomniac sleep cycles. And another good point, the WDs stay at bay for about 2 days!

If you are reading this and haven't tried loperamide for WD.. i strongly suggest that you take in next time you go CT. I also know that probably not everyone can feel effects from lope, and maybe i am just extremely lucky (or maybe all my previous ecstasy use has left HOLES in my brain for the lope to pass through).. but i thought i would just put it out there.

So, don't drop the lope just yet... it may just prove to save your ass one day like it's done for me three times now.:D


Hey PL, I suspect that you may be one of the lucky people who have a natural defficiency of P-glycoprotein. With the myriad of different things that can go on in the human body I don't see why this wouldn't happen to some people.

Flipside, I'm really glad this helped you. I kept W/D's away like this for a couple days myself!!!! Anything that helps is a valuable tool!!!


Not sure if you posted this but how many mgs of the nitrazole did you take? And did you have to up the lope dose as the days went on if you were still without?

Or could you maintain by re-dosing with the same combo and amounts of each? sorry if you already stated, i just didn't see it when I loked back over the thread. Thanks again for that neat little trick to get thorugh the BBB .

Papa Verine
12-10-2006, 11:17 AM
Not sure if you posted this but how many mgs of the nitrazole did you take? And did you have to up the lope dose as the days went on if you were still without?

Or could you maintain by re-dosing with the same combo and amounts of each? sorry if you already stated, i just didn't see it when I loked back over the thread. Thanks again for that neat little trick to get thorugh the BBB .

Hey flip, I took 400mg of ketoconazole to inhibit p-gp before taking my lope. 400mg worked very well. I don't know how long this will work for because I only did it a dose at a time. I mean I didn't try to keep taking more and more and more. When I was in W/D I always managed to get more of my DOC eventually and never had to use Lope for more than a day at a time. I wish I had more info for you but I hope this is helpful.

flipside
12-10-2006, 11:26 AM
^^ Thanks papa ver I also took 2 of the nitrozole tabs ( 2oo mgs each), so i guess i will just re-dose daily with the same combo for now. Thanks for all your help.

alowishus
01-11-2007, 12:38 PM
For those that have used it, did it work?
How much did you take?
How long before you felt any relief?
How long did it last?
How long before you took more?


Yeah I know......:rolleyes:

Just trying to get a understanding here.

lister40
01-11-2007, 09:05 PM
I've heard that it does work..

chemboy7
01-11-2007, 09:40 PM
Yeah, it works; not the way subs or Methadone or even benzos do.... but it's nice to have in your arsenal. Really the thing it helps most with is the gange gut and the mud butt, still gonna be feeling it though. Whenever I use it I drink the whole bottle (120 ml) at 1 mg per 5 ml so that would be about 50mg right, that sounds small... maybe that's why it hasn't been helping as much lately. You need alot, so swallowing pills is a bad idea; get the liquid and chug it. It not only coats your painful queasy stomach but also absorbs faster... it last quite long too, about all day if I remember correctly. One thing to remember though, a week or so after you stop taking it be prepared for the biggest, most jagged, tear your asshole apart chunk of shit to pop out of you... it's what I imagine giving birth would be like, except I have no hand to squeeze or doctors patting sweat from my forehead.

edit: "How long did it take to kick in?" - I felt better as soon as it was finished, not good but better... just knowing that it's going to ease up a bit. Kinda like how you feel better when you score and your still dopesick, like that. Really though I think it took a good hour, hour and a half to reach any adequeit plasma concentrations

"How long until you had to re-dose?" - I usually did it in the morning and then later at night right before bed, and I could have done without that really... just didn't want to wake up with the gange.

I wonder if one would get more acrossed the BBB and be more effective if the bottle was bummed instead of drank? Pass first pass metabolism and all those waiting blood vessels and shit waiting to suck it up. Anyone up for trying? I'll but the bottle.

alowishus
01-12-2007, 04:47 AM
Thanks for the image of you upside down w/ a bottle poking out of your ass, going glug, glug, glug like a water cooler. :D I needed the laugh. Karma points for you.

I don't know if I haven't hit it yet or what is going on, it's been over 48 hours since I had anything, other then the lope, I took 6mg, in the morning and 6 mg in the evening cuz well I wanted to damn it. :p

I'm achey, nose is stuffed, have no energy (never did), but the hot flashes & cold sweats are no where to be found, which is what I always go through and are the WORST for me. Thank god I'm not a women, if I had to do that hot flash shit all the time I'd put a 12ga slug in my head. Some either the lope kicks ass or I haven't hit the wall yet....... :rolleyes: :o :(

Narkotikon
01-12-2007, 06:09 AM
It helps for GI problems for me, but nothing else. I usually get a big generic bottle of Kroger's brand pills. I think they come in bottles of 40 or 50 or something like that. It's around $8.50 for it. When I take it, I usually take four or five 2mg pills at a time. I've had the mint-flavored liquid before, and it I think hits faster, but I usually get the pills for some reason. For me, it doesn't help with anything other than what it's supposed to do. It would be interesting if you could get ahold of some of those alterted loperamide nano-particles that are supposed to cross the BBB. I read that somewhere. I don't remember how they were altered, but they got across. For the legs and anxiety, I've been buying a bottle or two of wine and having a few glasses at night when I'm sick. It definately helps calm me down and makes my legs feel better, but it sucks for sleep. I mean, it makes me sleepy, but I always wake up and never get a restful night's sleep on alcohol.

jacky
01-13-2007, 01:16 PM
I know of one opiophile with a chroni pain condition that used loperamide daily in large doses to help supplement their other opiate narcotic pain relievers.

they contacted me cause they were really worried about having to get off of loperamide. seemd their new insurance wasnt going to cover the full cost of their prescription meds, so they were not now going to be able to afford buying loperamide in large quanititys.

they were taking upwards of 190 milligrams of loperamide daily.

they stated that the pain relief from loperamide was obvious, and that cutting the dose brought about increased pain. even when taking other opiates.

I dont know how much research has been done on the metabolites of loperamide, but there are two or three supposed active metabolites of loperamide. peak plasma levels are around 30 hours after the dose is taken, and a certian amount of loperamide is still found in the blood some 72 hours after dosing. maybe metabolites of loperamide need to be researched further?

there are opiate receptors all over the body, there are cells in other parts of the body besides the head that appear to be basically brain material, I keep saying this when I come across the loperamide disscusions, because I think that seperating the brain and body to a finite degree can be misleading when considering psychoactivity. a feeling of wellbeing, and neurotranmitter release can be created from such simple acts as smiling...so perhaps the action of loperamide in the body really can lead to increased euphoria or pain relief.
in one study done on loperamide, 10% of a control group of seasoned opiate addicts described mild euphoria from loperamide.
also take note that loperamide can be psychoactive as a sedative, it says right on the box that it can cause sedation.
when I take it I notice a stimulant action in the first 4 hours. I have noticed increased stamina when taking loperamide when I dont have enough opiates to get real loaded feeling. I would be at work, and getting chilly, with goosebumps not cause it was cold, but because I was on a substandard dose of opiates. taking loperamide abolished this completely. at the point of feeling ucomfortable from lack of enough opiates, I become withdrawn, but taking 30 or so milligrams of loperamide, I would feel better, and start motor mouthing it with my co-workers like I do when I am inebriated on opiates.

I remember billi contacting me excited a few years ago when he found that loperamide helped withdrawls...I was not aware of its limited opioid pharamcodynamics at that point. I was elated when I did the research and realized that though it had limitations, that loperamide was at least a legal opioid that had sedative effects possibly, and might take the edge off of withdrawls.

The only experience I had with loperamide before that call from billi, was some 5-6 years before.
I had taken loperamide once trying "cold turkey" heroin withdrawl at my ex-wifes parents house. but they controlled the meds, and taking the one loperamide that I took most likely wasnt enough to do anything...the next day we relapsed, so I would have had a chance to find out anything on my own about the substance.

I have used loperamide with my standard opiate dose when I was using psychoactive amounts of DXM, and it seems to augment the effects of DXM, that is just a far flung opinion, but I swear it enhances the experience.

some day someone will find a way perhaps to potentiate loperamide, get it passed the BBB, or use it as a precursor, but I think the drug at this point has some obvious uses. on countrys where people die from chronic diarhhea it might be a compassionate aid...here in the "1st world", perhaps it might reduce agony of drug withdrawl to a degree.
that chronic pain patient convinced me that something is going on with loperamide that is being overlooked, ignored, or maybe that some people havnt got the concept that we dont know everything about the human body and the drugs that we put in it, and the reactions that result.
this person was adament that it was a very important part of their pharmacopioid stash.
perhaps the brain/body interaction needs to be considered in a looser fashion. maybe endogenous opioid release is a result of loperamide having a mild analgesic effect at locale besides the brain? such things are known to happen as endorphin release just from mental exercise, meditation etc.

some brash souls insist that some people are wrong for suggesting that loperamide is more than a diarrhea. it doesnt take much to look at the box and notice it can have sedative effects. how might those sedative effects arise? that is anyones guess...but it is definitely a consideration that they might arise as a bybroduct of opioid agonist activity.

I know 1 person out of ten stating that they got euphoria from loperamide in a clinical study is not proof of loperamide being a psychoactive opioid.
but maybe we can gather information from our own population...
we could have a poll study....
over a certian amount of time. and let people vote in their particular reaction to loperamide. if we could get 20-30 people interested in this, then we might be able to observe some similiar reactions/ratios.
it is worth a try, and people could do it in their own time and such. maybe we could take the poll over a few months time.

RoadHead
01-13-2007, 04:23 PM
I know 1 person out of ten stating that they got euphoria from loperamide in a clinical study is not proof of loperamide being a psychoactive opioid.
but maybe we can gather information from our own population...
we could have a poll study....
over a certian amount of time. and let people vote in their particular reaction to loperamide. if we could get 20-30 people interested in this, then we might be able to observe some similiar reactions/ratios.
it is worth a try, and people could do it in their own time and such. maybe we could take the poll over a few months time.

jacky, this sounds like a great idea for not only loperamide but also for other natural (or unnatural) drugs. is this poll something that you are going to start? or is this poll going to be more like the kind of article that you would be putting in your newsletter/e-zine? maybe one or two polls in each edition and post the results in the next edition, along with online? that sort of thing?

i think this would be an excellent way to promote harm reduction and self preservation for those hard to handle "in between" times. i think there would be several people willing to help out in various assorted ways. some people have the experiences but not much in the ways of comp skills while others have the comp skills but not necessarily the writing skills and such. just some food for thought.

btw, thanks to you and billi for all you do for this whole community. the help and hope you give to all of us to make this hell we call life, a little more bearable and a lot more enjoyable, is more appreciated than we can ever repay you for. kudos to you both and may all your days be filled with happiness and happy nods. :)


to get back on topic now, yeah alow, it works for me for those times of need. i usually took a couple of swigs and usually felt effects from it within 20-30 minutes. liquid definitely works the best for me. usually lasted several hours depending upon the gorilla. when i felt them too familiar rumblings and burning, i took more, usually 3 to 4 doses daily for first few days. i rarely ate when w/d'ing cuz not much worse in my mind than flaming squirts. the only thing i wanted to feed was my gorilla, not the porcelain god.

kannibal4_2o
01-15-2007, 07:38 PM
Does anyone know a way to make Loperamide cross the bbb besides the polysorbate 80 method? There has to be some kind of cocktail out there!!!

devilsdrug
01-15-2007, 08:50 PM
nope , havent even heard of the ps 80 concooction

cronosaegis
01-15-2007, 10:02 PM
If you'll use the search engine, hell search for quercetin and loperamide, you'll discover that members have tried everything and seen it all fail.

From herbals like quercetin to using antibiotics to slam plasma levels to getting pure loperamide and acetylizing it- all attempts have failed.

If anyone would really have found anything that has worked, and not been deadly- ie mega doses of quinine and quinide or drilling a damn hole into the brain- the world heroin market would have been devastated.

Just be glad it's there for the king shits of withdrawals.

Papa Verine
01-15-2007, 10:16 PM
P-glycoprotein inhibitors.

Quercetin doesn't work. That's a myth. Google Quinidine and loperamide drug drug interactions.

kannibal4_2o
01-15-2007, 10:18 PM
i heard somewhere, dont quote me, that inhibitors/ bloodthinners such as verapamil would allow some across the blood brain barrier. Being that it is stronger than fentenyl its not something i would experiment with. But there are inhibitors out there that make alchohol soluable drugs cross into blood so why not with Loperamide? Not tryin to get flamed.... just wondering if anyone did some independent research on the subject, I always do my research befor asking... But thank you cronosaegis. I do appreciate all input. And your right, If there was an easy way heroin market would plummit and Loperamide would go SII in seconds flat if the public found out... But where theres a will- theres a way, and theres always someone out there that knows more than you. Some opiate crazed mad scientist is probably laughing as we speak!!

Papa Verine
01-15-2007, 10:24 PM
i heard somewhere, dont quote me, that inhibitors/ bloodthinners such as verapamil would allow some across the blood brain barrier. Being that it is stronger than fentenyl its not something i would experiment with. But there are inhibitors out there that make alchohol soluable drugs cross into blood so why not with Loperamide? Not tryin to get flamed.... just wondering if anyone did some independent research on the subject, I always do my research befor asking... But thank you cronosaegis. I do appreciate all input. And your right, If there was an easy way heroin market would plummit and Loperamide would go SII in seconds flat if the public found out... But where theres a will- theres a way, and theres always someone out there that knows more than you. Some opiate crazed mad scientist is probably laughing as we speak!!

Verampamil is a P-glycoprotein inhibitor. It will help lop cross the BBB but it's not the most potent P-gp inhibitor known. Quinidine ot Ketoconazole would work better. And lop. is not stronger then fent wether it crosses the BBB or not.

cronosaegis
01-15-2007, 10:31 PM
P-glycoprotein inhibitors.

Quercetin doesn't work. That's a myth. Google Quinidine and loperamide drug drug interactions.


No where, no where, no where did I say that quercetin worked. Nor was it implied. It's a fairly rare word that when combined with loperamide brings up most of the past discussions.

And for what it's worth to the casual observer...
I wouldn't just lightly suggest anyone to lay hands on quinidine, as it and quinine both can kill you and or cause serious damage. But, hell, this is a hard drugs board, so does that need saying ?

Papa Verine
01-15-2007, 10:38 PM
No where, no where, no where did I say that quercetin worked. Nor was it implied. It's a fairly rare word that when combined with loperamide brings up most of the past discussions.

And for what it's worth to the casual observer...
I wouldn't just lightly suggest anyone to lay hands on quinidine, as it and quinine both can kill you and or cause serious damage. But, hell, this is a hard drugs board, so does that need saying ?

You're right. It's a dangerous drug with dangerous side effects, but it will allow loperamide to cross the BBB by shutting down efflux of p-glycoprotein from the brain to the blood. This is widely accepted, and newer, safer P-gp inhibitors are being made right now for use in combination with chemotherapy drugs. But my own experience with ketoconazole and 40mg+ doses of loperamide resulted in a typical opioid response for me equivalent in effect to a low dose of methadone.

kannibal4_2o
01-15-2007, 10:42 PM
thanks, I read somewhere that it was stronger than fent, but I was wrong. Thank you for pointing that out. But it is close, read a few articles about coating nanoparticles with ps 80 and injecting, and mu bonding was strong like fent. and anelgesia and euphoria were present. Im definately not a chemist. But has anyone ever tried this with these inhibitors? Just curios, I only have easy access to verapamil. So how much would you have to take, would you take them at the same time? Been looking into this for a long time but never experimented with it, and i cant really find any straight answers. Would be a cheap fix for a dope sick person if it was possible to get some kind of euphoria out of it.

Papa Verine
01-15-2007, 11:00 PM
thanks, I read somewhere that it was stronger than fent, but I was wrong. Thank you for pointing that out. But it is close, read a few articles about coating nanoparticles with ps 80 and injecting, and mu bonding was strong like fent. and anelgesia and euphoria were present. Im definately not a chemist. But has anyone ever tried this with these inhibitors? Just curios, I only have easy access to verapamil. So how much would you have to take, would you take them at the same time? Been looking into this for a long time but never experimented with it, and i cant really find any straight answers. Would be a cheap fix for a dope sick person if it was possible to get some kind of euphoria out of it.

Do you want advice from a high school drop-out with no real medical or scientific experience?

Good.

I'd take a double dose of the Verapamil and 30 minutes later about 50mg of loperamide... myself...

HistoryofMadness
01-15-2007, 11:01 PM
if anyone's wondering, i've merged several posts about loperamide here. call it cleaning up, whatever. but everything you've ever wanted to know, and some shit that most likely isn't true, is in here.

Seedy
01-16-2007, 02:59 AM
^^
Holy crap I was wondering why it was so long!

alowishus
01-19-2007, 08:04 AM
^^ Me too.

Either my CT was the easiest I've ever had, or the lope is a gift from the junkie gods!!

I walked out untouched on the other side.....

Now it's just all in my head.:rolleyes:

lister40
02-05-2007, 03:26 PM
I snorted 4mg's of it and it made me sweaty like most opiates do at first to me.. I need to do some more, but I can tell it did something.. the small burn spot doesn't hurt as bad as it did.

HistoryofMadness
02-05-2007, 03:30 PM
i took a couple with some tagamet and a shot of dxm... weird buzz

Euphoricgirl
02-05-2007, 05:08 PM
So are you saying Hom that it will help little ol Egirl with her withdrawals??? Because I bought some, some bring me some good news huh?

HistoryofMadness
02-05-2007, 08:50 PM
So are you saying Hom that it will help little ol Egirl with her withdrawals??? Because I bought some, some bring me some good news huh?

yes if i were in WD right now, i'd have 2 loperimides, 2 tagamets, a double shot of dxm, and a good rinse of water over a pound of seeds...

ok maybe the last is too much but i could see how the others could help... i would get some kratom for sure. that's not too obvious if you just make them into capsules and put them up.

Euphoricgirl
02-06-2007, 07:24 AM
MUAH Hom. Always a help you are!!!

Opiyum
02-06-2007, 08:03 AM
If your really desperate (in full blwon withdrawals) and dont mind taking the most painful shit of your life go buy a bottle of the liquid Loper....Drink it all. youll be fine.

Euphoricgirl
02-06-2007, 09:11 AM
Thanks guys. Just took some loperamide and black cohosh extract, will let y ou know how it goes. Prayer for those of use in withdrawals.... :-)

prhighmalrage
02-06-2007, 12:03 PM
let us know how it goes, i'm very interested to see

Euphoricgirl
02-06-2007, 12:55 PM
Alittle buzz but not much of anything, may be the placebo effect. I just went out and bought what papa ver tried and gonna give that a go around and will update ya.

jacky
02-09-2007, 12:31 PM
hmmm, a good honest experiment in the works.

thanks for keeping us updated, play by play withdrawl abatement...is it possible?

hope you feel better.

L0VE
02-09-2007, 07:18 PM
long acting opiate agonist and anti diarrheal OTC drug called loperamide is structurally related to methadone. the drug has aboiut a 72 hour stay in the body, the merabolites of loperamide actually build to greater amounts on the second day after dosing. with 10 opiate experienced people taking the drug only 1 described any sort of euphoria from the drug. this interests me as this 1 in 10 number is described by some as a general consistant percentage of people who experience euphoria from other opiates. I talked to other opiophiles that have used loperamide to kick other opiate substances. I have used loperamide in conjunction with other opiates in an attempt to percieve any potentiation of those drugs. this loperamide is the only OTC opioid regularly offered without a prescription in the united states besides the irregularly supplied OTC codeine cough syrup. I have gone through some severe detox's unaware that this drug even existed. I notice a surge of energy when I consume loperamide initially, and have consumed it at work when starting to suffer anxiety/cold chills from cutting other opiates dosages. Its amazing to me that in a country where people insidiously avoid discussing opiate pharmacology that this drug is just hanging out, nowhere on the package does the product warn opiate abstainers that the product could encourage relapse etc. why cant he facts be presented first hand? probably because telling the truth would put the power in the hands of the masses. finally I wonder just what potentially more potent opioids may be synthesized from loperamide? I asked this question in the hive but the post went unanswered, and now the hive doesnt even exist. lopermide, the long acting, mild and legal OTC opiate goes basically unabused and perhaps underapppreciated. the antidiarrheal tag perhaps is associated with the mundane.

Are you serious? Loperamide does nothing for my withdrawls, except make my stomach stop hurting. ??. It's pointless and can not take away withdrawals or make you high.

alowishus
02-09-2007, 09:05 PM
Are you serious? Loperamide does nothing for my withdrawls, except make my stomach stop hurting. ??. It's pointless and can not take away withdrawals or make you high.


Helped my wd's a million fold, too bad it didn't work for you.
Has nothing to do w/ getting high, but everything w/ not rolling around in bed, soaked in sweat, can't sleep and in pain.

How much did you take? 10 mg was fine for me once a day.

HistoryofMadness
02-11-2007, 01:28 PM
i have a theory that loperamide helps people on a sliding scale... some a lot, some barely, and some none.

i have a lomitil, some loperadmide, some tagamet, and a decent herbal potentiator recipe. i might even throw in some dxm. i think i have a highly acute reaction to opiates... always have hit me harder than most...

so i'll try a few variations and see if anything interesting pans out... will post bioassy / experience report soon.

BizzyBone
02-26-2007, 05:17 PM
Im Just gonna report that i took 12 mg of lop And i am on my 3rd hour now and feel almost alright still achey a bit no stomach problems sweating once in a while like once every hour ...Other then that thighs just seem to aCHE A LITTLE BACK DONT HURT NO WHERE NEAR AS BAD AS IT USALLY DOES.....Sorry for caps, But all in all it gives me a crazy head high like a rush or maybe its my blood pressure from no opiates....Ive been doing about half a cup of grounds a day with some percs or tabs if i find them .......Didnt have nothing yesterday except 2 darvocets....And this morning i did 0.5 of bupe that i have been saveing for awhile ...Believe it or not i had a half of a quarter and broke that into and thought foursure that wouldnt help i snorted it this morning and it kept me feeling alright till i got home 8 hours shift and a lil over time so about 10 hours...I just got 2 norco 10's and took them ...i will report back ...hope fully buzz will be stronger

BizzyBone
02-26-2007, 05:20 PM
That is if i even feel 2 norcos ...with the tolernce i have ..And plus that little bit of bupe i did ...But that might be a reason the lop aint working as good as others ...Maybe Maybe not...But i dont think that matters with the lop because it dont go to ur brain as ive read it goes through your stomach i believe....

mrklean
03-09-2007, 09:09 PM
OK, Whoa. REporting in from DXM space this is captain klean. speaking. I am offficially spun on the syzurp and I'm gonna particiapate in the thread like it or not. I have no opi tolerance or habit right now. Would it be worth getting some ketonamuchacwulcallzit you know the inhibitor that is an antibotic and some loperamide and seeing what they do to a non tolerant individual? When you say its like a low dose of methadone I am interested. How low a dose? LIke 30mgs? I might go out and do and experiment if anyone would be interested in hearing about it. If you tell me 400mgs ket. followed with 40mgs lop. is equal or greater than 30mgs of methadone in effect on an individual with no tolerance then I will conduct the experiment whether you wanna hear about it or not. If this post makes no sense it is all the cough syrups fault.

mrklean
03-09-2007, 09:18 PM
Do you want advice from a high school drop-out with no real medical or scientific experience?

Good.

I'd take a double dose of the Verapamil and 30 minutes later about 50mg of loperamide... myself...

ROFL ,

I love this kind of advice. Listening to this kind of advice is how I got to where I am today. Atleast the advice wasn't from a junky this time. It just makes so much sense how can you not listen?

petal scars
04-21-2007, 09:43 AM
I've been using loperamide exclusively for two weeks now after finding a way to get it past the BBB. Here's some notes...

1. Loperamide is very strong but variable in it's effects due to the unpredictability of p-gp inhibition. The first time I got 16 mg past my BBB was close to the highest I've ever been. The day before I took 15 mg of Morphine and barely felt a thing due to residual tolerance.

2. The body seems to develop a tolerance for P-gP inhibitors faster than for opiates, but still this isn't easily predictable. One day the lope may only have a moderate effect at best and the next it may kick your ass.

3. High dose loperamide is not extremely constipating as long as it gets past the intestinal P-gp barrier. If it doesn't work that day you'll feel as if your guts have been trampled by a horse.

4. It's extremely long lasting with a slow onset. Two hours is a minimum to start feeling CNS effects, although it's usually more like four hours before it's good. It continues to escilate from there, going from good to great to super-awesome to "oh fuck, it's 20 hours later and I have to sleep but my respiratory system shuts down as soon as my head touches the pillow."

5. The hangovers are a bitch. At first I thought this might be mild neurotoxicity, but I'm kind of leaning against that intepretation as the eye twitches eventually ceased. But what do I know?

6. The inhibitor I use is not quinidine. I've never seen it discussed in relation to lope on any forums. If you manage to find out what it is, good for you. Remember that Loperamide will be scheduled or poisoned with apap if the secret is revealed. Don't let this go the way of poppy seeds.

7. I've given myself a case of diverticulitis experimenting with this stuff as both a methadone substitute and with various reputed inhibitors before I found the combination that works. It only took 12 mg a day for four months to fuck up my bowels. People who take massive doses without p-gp inhibitors are suicidal.

...

Lope might be just slightly stronger than morphine or it might be almost as active as fentanyl. I have no idea. It all depends on the degree of p-gp and enzyme inhibition you manage to accomplish. Remember: This shit is unpredictable in strength. This will wreck your intestines. It might be neurotoxic... and once you find out that you're a trip to the grocery store away from being high it's virtually impossible to resist despite the very real dangers.

alowishus
04-21-2007, 12:06 PM
I've been using loperamide exclusively for two weeks now after finding a way to get it past the BBB. Here's some notes...

1. Loperamide is very strong but variable in it's effects due to the unpredictability of p-gp inhibition. The first time I got 16 mg past my BBB was close to the highest I've ever been. The day before I took 15 mg of Morphine and barely felt a thing due to residual tolerance.

2. The body seems to develop a tolerance for P-gP inhibitors faster than for opiates, but still this isn't easily predictable. One day the lope may only have a moderate effect at best and the next it may kick your ass.

3. High dose loperamide is not extremely constipating as long as it gets past the intestinal P-gp barrier. If it doesn't work that day you'll feel as if your guts have been trampled by a horse.

4. It's extremely long lasting with a slow onset. Two hours is a minimum to start feeling CNS effects, although it's usually more like four hours before it's good. It continues to escilate from there, going from good to great to super-awesome to "oh fuck, it's 20 hours later and I have to sleep but my respiratory system shuts down as soon as my head touches the pillow."

5. The hangovers are a bitch. At first I thought this might be mild neurotoxicity, but I'm kind of leaning against that intepretation as the eye twitches eventually ceased. But what do I know?

6. The inhibitor I use is not quinidine. I've never seen it discussed in relation to lope on any forums. If you manage to find out what it is, good for you. Remember that Loperamide will be scheduled or poisoned with apap if the secret is revealed. Don't let this go the way of poppy seeds.

7. I've given myself a case of diverticulitis experimenting with this stuff as both a methadone substitute and with various reputed inhibitors before I found the combination that works. It only took 12 mg a day for four months to fuck up my bowels. People who take massive doses without p-gp inhibitors are suicidal.

...

Lope might be just slightly stronger than morphine or it might be almost as active as fentanyl. I have no idea. It all depends on the degree of p-gp and enzyme inhibition you manage to accomplish. Remember: This shit is unpredictable in strength. This will wreck your intestines. It might be neurotoxic... and once you find out that you're a trip to the grocery store away from being high it's virtually impossible to resist despite the very real dangers.


I just don't know what to say to any of that....
Besides that you have only said you broke the "lope code", proving it is different.

I'll stick w/ safer (to a degree) already illegal things that come all in one package and have a consistent effect w/ less badness over all. :D

petal scars
04-21-2007, 12:25 PM
I just don't know what to say to any of that....
Besides that you have only said you broke the "lope code", proving it is different.

I'll stick w/ safer (to a degree) already illegal things that come all in one package and have a consistent effect w/ less badness over all. :D

A good idea. It's inevitable that someone soon will figure out the same thing I did, so I'm not interested in proving anything. I just want to tell people the good and bad of this before that happens, and especially let people know that this stuff isn't Darvocet.

jacky
04-21-2007, 01:09 PM
I think that this drug is active in the brain even without p-gp inhibitors for some people.
I usually get a small stimulant action when taking loperamide, and then later sedative activity that is quite noticeable.

then I used it a few times for withdrawl from standard opiates.

know a chronic pain patient that couldnt deal without the loperamide in conjunction with other strong pain meds.

and some data suggests that a % have had euphoric effects presumably attributed to the loperamide ingested.

I would like to see a study on the bbb permiability of all of loperamides metabolites...the metabolites continue increasing for around 32 hours, and decrease substantially around 70.

so I am a believer that the drug has its uses.......and that there is probably alot concerning the pharmacokinetics that that we still dont know.

I think the packaging needs to mention opioid agonist effect, just for the consumers safety...should a recovering addict not know that this material has even somatic opioid effect? now it looks like some education about p-gp inhibitors might/should be included, that is, when enough interaction with the compound allows for more research.

so I am for MORE communication of the possibly harmful effects of consuming this drug with any combination.

has grapefruit juice made poppy seeds illegal yet? I dont know, maybe in some areas, doubt it though, poppy seeds still to this day remain culturally mundane to most people, there would have to be major attention on the media's part for this to escalate much more. the mythbusters even did a positive analysis of poppy seed products consumed on camera...hey, morphine and codeine consumption without a prescription on prime time cable everyone!!!....but no one really said anything about it.
I knew years ago when the poppy seed tea thing came to my attention that it might be a well guarded secret to some.....but with people dying all around me from heroin overdose/alchohol related deaths, I figured that things have become bad enough with the drug wars deletirious effects on communication/education about drugs and interaction with them that we need all the info we can get.

if there is a drug/compound that interacts with loperamide in a strong way, let us know.......if you are against spreading info that might harm someone I understand that, but in the end, only communication, education, and EMPOWERMENT and action will help make things better.

its a hard battle of the mind to warrant what to share with society, and what not to share. at one point some of the people within the research community that I deal with were open and sharing in a scientific sense. now I see secret recipes, blind consumption, and it can only lead to a drug culture that is ignorant, foolish, and acting on blind info. pet names, advertising schlock dont let you know how a product might interact with other compound.

now we will still, and have had others get interested in the p-gp inhibitor potentiation/pharmakinetic augmentation of loperamide....and a few souls will go there, and probably try anything that might share that activity. I am fairly ignorant of all the different compounds that have that specific activity, and really dont see me needing to try and get a lift off of loperamide for any reason besides using it for withdrawl, or for its intended purposes.

definitely a novel subject.

the cp patient that used up to a 200 milligram amount a day in conjunction with other opioids/opiates told me they feared withdrawing from the drug when they could no longer afford to pay for that much a day, so perhaps using loperamide even without a p-gp inhibitor is addictive long term

thanks for the info that you do share, its interesting, and slightly disturbing in the sense that now I can "see" some scenarios that have "probably" taken place when people consume loperamide with the wrong substance......crazed euphoria, saying the wrong thing at the wrong time.....or maybe all out retching opioid induced sickness....comas...death.

alowishus
04-21-2007, 01:21 PM
We can take it to the chem forum, er wait is that forum open? Or does it has it's access restricted?

80oranges
04-29-2007, 09:11 PM
Have you been using any kind of opiate before you started getting high with loperamide?

flipside
04-30-2007, 03:51 PM
*BUMP * for Jah

JahRed24
04-30-2007, 04:08 PM
loperamide is a potent opioid agonist, allthought because it's Too soluble in water it dosent pass the blood/brain barrier and is only of use as a cure for diarhhea. If given intrathecally or intracranially it dosent have to pass the barrier and therefore works as a potent opioid agonist.


i hear if u snort it that it may in fact actually cross the blood/brain barrier...is this true? :confused:

flipside
04-30-2007, 04:13 PM
Check out paragoric kid's posts on the first page.

The short answer appears to be yes.:)

80oranges
04-30-2007, 08:35 PM
i have tried snorting lop, and it definetly does not work...if it were that easy it wouldnt be otc

JahRed24
05-01-2007, 08:54 AM
lol did u just try doing it after i made that comment? if u read on wikipedia it will say that about it.

Papa Verine
05-01-2007, 11:54 AM
There's only one way to get Loperamide across the BBB.

Take 100mg and stand on your head for 2 hours.

Serious...

flipside
05-01-2007, 12:09 PM
There's only one way to get Loperamide across the BBB.

Take 100mg and stand on your head for 2 hours.

Serious...

:D

JahRed24
05-01-2007, 02:28 PM
or ill just say fuck it and go get my tramadols...i think those will be a better drug for me to take in the near future...:cool: i've just been puffin all day today so im stoned...


<<<i had to get high for my post number: "420" lol ..shit

Brony
05-01-2007, 02:35 PM
There's only one way to get Loperamide across the BBB.

Take 100mg and stand on your head for 2 hours.

Serious...

hahaha :D

Papa Verine
05-01-2007, 03:04 PM
hahaha :D

I knew you guys were going to laugh at me but I actually tried it. When I learned there was an OTC opioid with some string attached I was pretty determined to get it in there. I figured it was worth a try. I watched "The Sheild" up-side down as I remember it...

80oranges
05-01-2007, 09:48 PM
haha...did it work? No really i have tried blowing Lop many times and it really doesnt do anything. It is alright for WD, but other than that you have to take it with a Protease inhibitor, which actually works. There are other ways that are completley un-practical for your average junkie, but the best way to do it is expiriment.

Skript
05-01-2007, 11:07 PM
This thread should be closed.. Theres a ton of valuable information in the first half dozen pages... Probably the most informative loperamide thread you could find on the net.. Now its just a bunch of jibber jabber...

Chemical_Boy
05-01-2007, 11:25 PM
I knew you guys were going to laugh at me but I actually tried it. When I learned there was an OTC opioid with some string attached I was pretty determined to get it in there. I figured it was worth a try. I watched "The Sheild" up-side down as I remember it...

How'd that turn out for you??

:D:D:D

Papa Verine
05-02-2007, 09:02 AM
This thread should be closed.. Theres a ton of valuable information in the first half dozen pages... Probably the most informative loperamide thread you could find on the net.. Now its just a bunch of jibber jabber...

Go ahead. I've explained loperamide drug-drug interactions with P-glycoprotein inhibitors in the other threads. (The only thing I'm sure worked for me) Never mentioned the "Standing on my head" thing before but I think I remember it working. At least I thought so, which is good enough sometimes.

When I'm dope-sick I'll take some placebo-effect anyday to take the edge off.

SomniGod
11-22-2007, 02:19 AM
If one were truly gonna kick, will loperamide have any chance of prolonging the WD's? Being an opiod, I am a lil sketched on taking 20 immodium daily for the next 2 weeks while i kick..... i just don't want to prolong my kick, ya know? I just don't wanna substitute one drug for another....I wanna feel ok, by myself.... This may not be the best thread to post this in, but it seems to be the best info on loperamide. So...?


~S~

limitless_euphoria
01-23-2008, 08:08 AM
Okay, so I spent like AN HOUR literally reading through this thread. It's an awesome one, BTW. Just the thought of making loperamide cross through the BBB gives me a chubby as I'm typing about it. :)

Now, for w/d, what do any of you who SWEAR by this stuff reccomend for dosages? Are we talking 20 mg, 40 mg? Something CRAZY??? Also, how much to dose how long after last use of opioid substance?

A friend of mine has been using some opies and wants to chill for a while. Just wanted to know what I should say to him.

Ron-Doe
01-23-2008, 09:27 AM
Okay, so I spent like AN HOUR literally reading through this thread. It's an awesome one, BTW. Just the thought of making loperamide cross through the BBB gives me a chubby as I'm typing about it. :)

Now, for w/d, what do any of you who SWEAR by this stuff reccomend for dosages? Are we talking 20 mg, 40 mg? Something CRAZY??? Also, how much to dose how long after last use of opioid substance?

A friend of mine has been using some opies and wants to chill for a while. Just wanted to know what I should say to him.
i use as directed for dia works ok no miracle tho

Nate
01-23-2008, 09:36 AM
Personally I was taking 12mg a day and a great deal of the physical symptoms were releaved. I always figured because although lopermide doesn't cross the BBB, it is hitting the other receptors throughout the body.

I have read of people taking higher doses...I guess it's whatever works for you, for some people lopermide really helps, for some it just releaves the nasuea and runs.

limitless_euphoria
01-23-2008, 02:59 PM
Personally I was taking 12mg a day and a great deal of the physical symptoms were releaved. I always figured because although lopermide doesn't cross the BBB, it is hitting the other receptors throughout the body.

I have read of people taking higher doses...I guess it's whatever works for you, for some people lopermide really helps, for some it just releaves the nasuea and runs.

Well SWIM, ahem, yeah my buddy Fred as usual. He took 2 NyQuil with 30 mg dxm and then 10 x 2 mg immodium pills. :) Oh yeah. Kept the monsters at bay for a while. Maybe whomever mentioned lope & dxm was on to something! Throw in benzos and you've got it made (Fred said he took a 10 mg valium on top of everything).

Chicago
01-23-2008, 04:51 PM
This never helped any w/d from going away at all.
But since some of the people of the op no alot about this, so my question is this.
When I start to take my lop soon for my detox, I will also be taking a little amount of subutex for a few days, so should I wait till after taking my subutex to dose on lop if need for my stomach problems to stop the runs, or does this not matter, b/c the way I read this & if some people swear that this does work, I will not dought u at all, every one is diff, but if as said, then it could affect in some way starting the subutex?
I no when the subutex is already in the body you are kool, but I'm asking b4 starting the subs would I really have to wait till needed for the runs after the dose, or does it not matter if taking right b4 subs or does it?

limitless_euphoria
01-23-2008, 04:59 PM
Now, does anybody find if they already have a substantial dose of lope in their sys and they go back maybe 18-24 hours later and use opiates that it actually less becomes more and you get wicked super blasted high? I was just wondering, that's all. :)

Scoutii
01-25-2008, 05:58 PM
This never helped any w/d from going away at all.
But since some of the people of the op no alot about this, so my question is this.
When I start to take my lop soon for my detox, I will also be taking a little amount of subutex for a few days, so should I wait till after taking my subutex to dose on lop if need for my stomach problems to stop the runs, or does this not matter, b/c the way I read this & if some people swear that this does work, I will not dought u at all, every one is diff, but if as said, then it could affect in some way starting the subutex?
I no when the subutex is already in the body you are kool, but I'm asking b4 starting the subs would I really have to wait till needed for the runs after the dose, or does it not matter if taking right b4 subs or does it?

This is how how I have used lopermade in the past. I like to wait until I fully detox my bowels if you know what I mean. I like to make sure I have at least run to the bathroom once. It is a personal thing I know nothing worse that drinking only purple Gatorade and wondering wtf just happened in the toliet. I will never ever kick with out lopermade. I have found that it does help with the other opiate receptors in the body and gives relief. I typically take 10-12 megs and have found about every 12 hrs I need to dose. The next time I kick I am going to use more Lopermade and see if I can get some additional relief with the RLS in the legs etc.

Scoutii
01-25-2008, 06:05 PM
Now, does anybody find if they already have a substantial dose of lope in their sys and they go back maybe 18-24 hours later and use opiates that it actually less becomes more and you get wicked super blasted high? I was just wondering, that's all. :)

Nope I haven't found that to be the case it is an interesting idea. Could always does up on some Lopermade get my plasma levels up and stable maybe 12 hrs after taking it? Then take my DOC an see what it does? I don't think taking them together would be any benefit. Most likely I am just setting myself up for hot one on one action with the salad tongs and a mirror.

So if my other opiate receptors in my body are being addressed by the Lopermade. Does that mean when I dose my DOC there is more opiate for the receptors in my brain since the ones throughout my body are being filled by the lopermade. Will that mean that all my DOC will bind and latch on to my brain opiate receptors since it doesn't have to share with my body or can Lopermade be easily kicked out of the other receptors.

BAH I will just get the Salad Tongs and Mirror ready and DO IT !!! BTW Generic Lopermade Liquid Gels for the WIN !!!

GOLD N DIEMONDS
01-25-2008, 06:58 PM
Nope I haven't found that to be the case it is an interesting idea. Could always does up on some Lopermade get my plasma levels up and stable maybe 12 hrs after taking it? Then take my DOC an see what it does? I don't think taking them together would be any benefit. Most likely I am just setting myself up for hot one on one action with the salad tongs and a mirror.

So if my other opiate receptors in my body are being addressed by the Lopermade. Does that mean when I dose my DOC there is more opiate for the receptors in my brain since the ones throughout my body are being filled by the lopermade. Will that mean that all my DOC will bind and latch on to my brain opiate receptors since it doesn't have to share with my body or can Lopermade be easily kicked out of the other receptors.

BAH I will just get the Salad Tongs and Mirror ready and DO IT !!! BTW Generic Lopermade Liquid Gels for the WIN !!!

WHAT A TROOPER! i hope you don't need the salad tongs though:D

alowishus
03-13-2009, 09:28 PM
Keeping this in the open for folks.

JonnyM
03-13-2009, 10:27 PM
Now, does anybody find if they already have a substantial dose of lope in their sys and they go back maybe 18-24 hours later and use opiates that it actually less becomes more and you get wicked super blasted high? I was just wondering, that's all. :)


I've done this and I can def. say it helped potentiate a hell of a lot.

however I am strange in the fact that with some grapefruit juice, and about 150mg of loperamide can make me feel pretty damn good. I dont have any signs of withdrawal, and everything is ok. I once had a friend try about the same dose and it did nothing, however I have heard of something similiar with other people to my experience before.

I say give it a go, you really have nothing to lose.

jacky
03-14-2009, 12:43 PM
from the data that I have read, with the loperamide orally taken, the peak plasma levels are around 32 hours after ingestion.
and the drug in pretty much out by 72 hours.

so if you dont feel something within the first 12-24 hours really, and then have a stronger reaction to other drugs, dont be suprised.

personally, I can feel a stimulant effect, and lessening of withdrawl just after a few hours of taking loperamide.
its not a 100% cure...but it helps alot, especially paired with other substances/herbs for detox.

also, I dont think much research has gone into the metabolic products of consuming this substance...there are metabolic products, are they active? its possible.

tch2296
03-17-2009, 12:40 PM
Having recently read about loperamide, I decided to give it a try to stave off my own withdrawals. I had been using maybe 1/3-1/2 gram of heroin per day for around a month, and entered detox 10 days ago, where I was given bupe. They released me with a small take-home supply (5 x 2mg doses).

4 days ago I took my last dose of bupe, and I woke up after two hours of sleep last night with bad restless legs, very lights sleep, GI discomfort, etc.

This morning, I was feeling even worse, yawning and sweating, feeling sensitivity to cold and pain, bad GI discomfort, and general just feeling shitty. It was apparent the bupe was pretty much out of my system. I took 96 mg loperamide around 10:30 this morning, so like 4 hours ago now.

After about 2 hours, GI problems were gone, and a lot of the physical stuff (yawning, sweating, gooseflesh) were getting a lot better too. Now, I feel like almost all the withdrawal effects are gone. I really just feel fine.

I am also starting to notice that the anxiety, restlessness, and discomfort have almost completely faded away as well. Additionally, I can feel the sort of heaviness in the eyes that usually accompanies an opiate high for me. I am far more relaxed and have stopped smoking cigarettes like every 5 minutes and squirming around.

This is the first time I have taken loperamide during withdrawals (never even taken it just to help w/ GI stuff), and I am very surprised. I realize there is a great amount of debate about whether any of the loperamide can cross the blood-brain-barrier, but I think the relief that it provides simply by its action on the peripheral nervous system is what's important.

Maybe the buzz some people report after taking a huge amount has something to do with the enormous relief on the PSN, even though it isn't really working for the CNS. I don't feel any euphoria, but I certainly feel relaxed, and from what I have heard it might take longer to fully take effect anyways.

Definitely wish I had known about this before....

JonnyM
03-17-2009, 01:14 PM
I took 96 mg loperamide around 10:30 this morning, so like 4 hours ago now.


I'm a firm believer in loperamide. I think you might try a little higher dose next time, and then report back in if you feel anything.


Im interested especially since I CAN get a buzz from it.

hovadagod
03-18-2009, 03:48 PM
But is it hard to taper imodium? I found that it was. Not too hard but it's very long acting. Kratom or imodium for WD's???

Spork
08-31-2009, 09:39 AM
I took 96 mg of loperamide yesterday with two tagamet and a bit of DXM (60mg) and to my complete shock, I actually got a buzz from it.

My back pain went away, my opioid cravings were gone, and I felt an electric glow, it was different from most opioids I have felt, it lacked a smoothness, it felt more "electric" if that makes any sense.

It was very shocking to me, I had taken 72mg of it once and nothing happened at all.

As for "not shitting for a week" I had no problems in that department last night, nor this morning :p

hovadagod
08-31-2009, 03:11 PM
that's a damn lot. be smart people. I don't think anyone's really studied high dose immodium use but i wouldn't use it to get a buzz. Next thing you know it will be moved behind the counter. Just be careful. But i'm glad it worked for ya. It should work for anyone with a little patience.

okie dokie
08-31-2009, 03:19 PM
But is it hard to taper imodium? I found that it was. Not too hard but it's very long acting. Kratom or imodium for WD's???


that's a damn lot. be smart people. I don't think anyone's really studied high dose immodium use but i wouldn't use it to get a buzz. Next thing you know it will be moved behind the counter. Just be careful. But i'm glad it worked for ya. It should work for anyone with a little patience.

it is not hard for me to taper off lope. i can cut my dose IN HALF each day (every 24 hours) no problem
40, 20, 10, 5, none

i have never caught a buzz from lope. the time i took 96 mg's i was expectin to get a mild buzz, but i just got out of wd's

Spork
08-31-2009, 04:39 PM
I think tagamet is key, as I remember reading that loperamide is heavily first pass metabolized.

okie dokie
08-31-2009, 04:52 PM
I think tagamet is key, as I remember reading that loperamide is heavily first pass metabolized.

"Loperamide molecules do not cross the blood-brain barrier (http://en.wikipedia.org/wiki/Blood-brain_barrier) in significant amounts, and, thus, it has no analgesic (http://en.wikipedia.org/wiki/Analgesic) or euphoric properties. Any that do cross the blood-brain barrier are quickly exported from the brain by P-glycoprotein (http://en.wikipedia.org/wiki/P-glycoprotein) (Pgp), also known as multidrug resistance protein (MDR1). Tolerance in response to long-term use has not been reported. However, loperamide can cause a mild physical dependence (http://en.wikipedia.org/wiki/Physical_dependence). Symptoms of mild opiate withdrawal have been observed in patients abruptly discontinuing long-term therapy with loperamide. For this reason, the drug was briefly classified as a Schedule V controlled substance (http://en.wikipedia.org/wiki/Controlled_substance) upon its introduction.[citation needed (http://en.wikipedia.org/wiki/Wikipedia:Citation_needed)]"


http://en.wikipedia.org/wiki/Loperamide

Spork
08-31-2009, 07:07 PM
We've all read the Wikipedia article on loperamide, okie-dokie, what are you trying to convey?

The p-gp pump can be oversaturated with a drug, allowing some of it to cross into the brain.

jacky
09-01-2009, 02:31 PM
one report/study I read showed that 1/10 people that have had a history with opiate use found loperamide to be euphoric.
it also showed that plasma levels peak after 30 some hours.

people should also consider the metabolites of loperamide...to my knowledge...not alot of research has gone into the metabolite study.

I can feel loperamide at rather low doses. it gives me a bit of a stimulant effect. it helps withdrawal a bit, and it also sedates me after 10 or so hours.

it says right on the box that the compound can sedate people....its obviously psychoactive to some folks. but maybe their mind is centered more in the stomach than most of us.

when I was a daily DXM user, I also noticed a synergy with loperamide.

we are damn lucky to have this compound as an OTC. I agree.

and as I usually spew, we did have one chronic pain suffering member here that used loperamide for chronic pain alongside morphine. when their morphine wasnt covered as much by their insurance, they were scared because they wouldnt be able to afford their loperamide. they suffered withdrawal even when on morphine if their loperamide was cut.

we have brain cells in other parts of our body than just in our skull, we also have opiate receptors all over our body...I reckon that the body and mind isnt as seperate as we like to think.
for some, loperamide has some suprises.

Papa Verine
09-01-2009, 02:54 PM
The most I've ever taken in one day was 200mg+400mg of ketoconazole (A P-glycoprotien inhibitor). I had a dope habit at the time and this combo completely eliminated my withdrawal symptoms. However, for the next several hours I had severe nausea that wouldn't let up. I never actually vomitted, just felt like I was going to for many hours.

Way, way back in the day, before I ever had an opiate tolerance, I could get a methadone-like effect from 40mg of loperamide with the ketoconazole. Weak, but definately noticable and it lasted for hours and hours.

I've never felt any effects from loperamide without a P-glycoprotien inhibitor.

chopstix
09-01-2009, 03:10 PM
^^ The last 3-4 times I've taken Loperamide, I've felt sick to my stomach for most of the day.. I'm sure there's something about it that fucks with my gut.. I usually take about 80mg..

okie dokie
09-01-2009, 03:49 PM
The most I've ever taken in one day was 200mg+400mg of ketoconazole (A P-glycoprotien inhibitor).

......and where can i get some of this ketoconazole???

JonnyM
09-01-2009, 03:55 PM
Like I've said before Loperamide gives me a slight buzz and removes withdrawal symptoms at a pretty high dose of +90mg's.


I'm not sure why it does the trick for me, but I have heard of others with the same experience.


Its really a life saver in w/d... I can continue life like normal.


We have many many threads dedicated to this strange opiod.

hovadagod
09-19-2009, 09:39 AM
If imodium is really easier to taper than other drugs there should be trials for using it to treat addiction. Think about the potential if it really doesn't cross the BBB. It sedates me a bit but nothing much. I remeber a long time back SWIM purchased pods on his lunch break one day when working and but got sick at work so he took a bunch of imodium (only 8-10mg max) and his cravings for hte pods went way down. He almost regretted purchasing them but was excited to do them nonoetheless.

In my experience imodium really cures WD 100% in doses under 20mg. More like 10mg usually. taken twice daily. Probably a good way off suboxone and maybe evben methadone(?).

This thread is like 4 years old now.

doctor diesel
09-19-2009, 10:55 AM
In my experience imodium really cures WD 100% in doses under 20mg. More like 10mg usually. taken twice daily.


Is this for real? Are you kidding us? Is there maybe a zero missing off that 20mg figure? :(


Doc

hovadagod
09-19-2009, 10:57 AM
Maybe I've never tried it after doing H for a while but I've done it to help huge 200mg hydrocodone habits.

JonnyM
09-19-2009, 01:54 PM
Maybe I've never tried it after doing H for a while but I've done it to help huge 200mg hydrocodone habits.

and it cures me 100+ oxy a day withdrawals at about 80mg.

okie dokie
09-25-2009, 11:58 AM
we all know that if you mix Loperamide with Polysorbate 80 (Tween80™) it may/will cross the BBB, well turns out there is Polysorbate 80 (Tween80™) in the NEW swine flue vaccine......i am just sayin....

http://articles.mercola.com/sites/articles/archive/2009/09/19/The-Truth-about-the-Flu-Shot.aspx

What is in the Regular Flu Shot?


Egg proteins, including avian contaminant viruses
Gelatin, known to cause allergic reactions and anaphylaxis are usually associated with sensitivity to egg or gelatin
Polysorbate 80 (Tween80™), which can cause severe allergic reactions, including anaphylaxis
Formaldehyde: a known carcinogen
Triton X100: a strong detergent
Sucrose (table sugar)
Resin, known to cause allergic reactions
Gentamycin, an antibiotic
Thimerosal: mercury is still in multidose vials

Paregoric Kid
09-25-2009, 12:19 PM
polysorbate 80 is very common, hell its in many kinds of eye drops and ice cream. the process by which loperamide can cross the BBB is nowhere near as simple as mixing polysorbate 80 with loperamide. the loperamide is attached to polybutylcyanoacrylate (PBCA) nanoparticles, that is what is important. after the loperamide is attached to the PBCA nanoparticles it should be able to cross the BBB. the polysorbate 80 is merely used as an emulsifier to make the PBCA-loperamide injectable due to loperamide's poor water solubility.

hovadagod
09-25-2009, 04:36 PM
Polysorbate 80 also helps hair loss!

Tha1der
10-15-2009, 05:29 PM
I just want to post my 2 cents on this topic.

Loperamide is honestly a life-saver for me. Lately it is very hard to consistently have opies, and so i spend alot of time without them, after having a good stash for a couple weeks. This has been going on for about 6 months. Im on opies enough that I will start WD's about 20hrs after my last dose (sometimes earlier). I have a very good job, but one that I have only had for a few months, so i dont have time for sick days. Luckily I found the information on this site about the benefits of loperamide, and was able to pick some up.

I was in WDs for about 30hrs, and was going through what all of us hate. The dia, the goosebumps, non-stop yawning, hot and cold flashes, the restless legs, insomnia, and bad depression. I took about 50mgs of Lope with about a 200mg of Oxy a day habit. The lope after only a couple hours, had stopped the awful diahrea, stopped my yawning, stopped the anxiety and restless legs, and I was able to get a good nights sleep.

Ever since that, I ALWAYS have a bottle of the lope pills around. One at my office, and a bottle at home. Since then, I have had many times of running dry on opies, and having to face WDs. The first day, i will take the highest dose which is usually around 50 mgs of lope, and then the following days after I will go down to about 20mgs.

Now granted, the first couple days are not great... The WDs are still there, but VERY mild. We all know how bad Oxy WD can be. For me it is the worse of any opies i have taken. Oxy WD starts very quick and very strong. But the lope absolutely cuts the WDs down to just a fraction of what the WDs usually are.

I cannot stress enough how much people who havent tried this, need to. There is no reason to go through the raw un-medicated WDs. Im sure im not the only person who doesnt have access to benzos, or low potency opies to help them taper the WDs. When im out, im out... and the only thing that Ill have access to is the Loperamide.

For those of you who havent tried this, its absolutely an option that should not be overlooked. I know it is hard to believe for some of you that there is an over the counter solution to WDs, but there is.

Thanks for letting me share this story. And i hope some of you out there that may be facing WDs give this a try.

I havent ever had uncomfortable constipation or an impacted bowel, like some people have "warned" of. It may seem like you are taking alot of lope, but it really is something you need to try for yourself and see what mg a day will work for you. But i wouldnt worry too much about serious health issues if you are under 50mgs a day.

Thanks,

-1der

More Feen
10-16-2009, 12:28 PM
Could getting Loperamide 'cross the BBB BE this simple??? (from Wiki)

Crossing the blood-brain barrier
Concurrent administration of P-glycoprotein inhibitors such as quinidine (http://forum.opiophile.org/wiki/Quinidine)(mainly and proven to work), Omeprazole (http://forum.opiophile.org/wiki/Omeprazole)(Prilosec OTC) & even black pepper with loperamide has been found to produce respiratory depression, indicative of central opioid action. [6] (http://forum.opiophile.org/#cite_note-5)

It really cannot be as simple as Pepper or otc Prilosec, can it?

M F

Be careful, don't kill yourself for science, science wouldn't kill itself for you!

HydroApe
10-16-2009, 12:37 PM
I don't know........but I'll let you know soon ;)

More Feen
10-16-2009, 12:42 PM
I don't know........but I'll let you know soon ;)

Hey Monkey Man--Hydro Ape!

Go easy on the lope after inhibiting the pgp--okay, start low dose, so you don't go into respiratory arrest--okay!

Let us know. US Gummimint, get ready to confiscate all the Loperamide on all the shelves, and to schedule it CII !!

The masses have found an easy way to get off on that shyte!

M F

doctor diesel
10-16-2009, 01:00 PM
I wonder what happens in lope is injected straight into the spinal fluid?
Seventh Heaven??


Doc

The Paregoric Man
10-17-2009, 07:22 PM
Here is what I have trouble understanding, if you're taking 100-200mg of loperamide at a time to help with WDs the absolute cheapest you'll find those amounts at retail in the US is about 10 USD at walmart.

10 USD for something that might work seems well silly since if you're in the US you have better options like pods or poppy seed tea that can be cheaper and let me tell you there is doubt opium isn't placebo.

And if you're not in the US you might have better OTC options than lope such as codeine or diphenoxylate, I know pods and poppy seeds are not sold/are illegal in much of the world.

For someone in the US to spend $50 USD on a couple days worth of loperamide when pods and seeds are cheaper and more effective doesn't seem cost effective.