Acetylation of Loperamide and Methadone

[Paregoric Kid]

I was wondering if it is possible to add an acetyl group to loperamide and if this would have any effect on it's ability to cross the BBB?
my other question was if you acetylate methadone would you get alpha-d-acetylmethadol? or what would you get?

[Zoop]

DUDE. TOTALLY. I have pondered the same question. I think what you'd get if you make O-acetyl loperamide is a pretty good opiate agonist with central nervous system activity. There is a drug that goes by the acronym PEPAP, which is very similar to what O-acteyl loperamide would look like, except stripped-down. PEPAP briefly was sold as a designer drug back in the 80's.

Anyway, I posted something about this on this forum a little while back - I can't remember what the initial thread was...

If you are going to make O-acetyl loperamide, you HAVE TO have either acetic anhydride or acetyl chloride, both are "watched" as they can be used to make heroin. I have purchased acetic anhydride from a company called "---" out of ---. I am pretty sure DEA only monitors large amounts of acetic anhydride being bought and sold. You can get 120ml of acetic anhydride from --- for about 30 bucks + shipping. You don't need much. I highly recommend ---.com - they don't ask no questions about nothing. Great for hobbyists like us.

Well, this company "---com" sells pure loperamide HCl too! I ordered some and was told that it's on back-order with an overseas manufacturer (probably in Asia). This was back in June. I waited and waited and finally cancelled my order for the loperamide, but the past few days I have been meaning to call them up and ask if they ever got it in.

I was going to tell them that I was treating irritable bowel syndrome (IBS) with the loperamide and it's drastically cheaper if I just buy it in bulk pure form rather than piddly little 2mg tablets, because the dosages for IBS treatment are on the order of like 14mg - seven tablets of Immodium.

Well, the reaction would be extremely simple, just mix the loperamide powder with straight acetic anhydride. A small amount of pyridine is needed in the mix if you really want FULL acetylation. Pyridine's not watched, and --- sells it too.

I have tried reaction of acetic anhydride with pulverized Immodium AD tablets and was able to get a product. I did a couple big rails of it and I think I could barely feel some type of opiate effect.

O-acetyl loperamide I think would need to be about 25-50mg to be a good hit.

This is absolutely intriguiging and I think it may be the next big thing if a reliable source of pure loperamide becomes available.

But to answer your question, YES, you'd get a "drug" from acetyation of loperamide. I am almost 100% certain of that.

[Zoop]

PK, pm me if you want to know what the redacted portions of my post say.

[Paregoric Kid]

also interesting is that hydromorphone can be acetylated and so can hydrocodone which creates a drug called thebacon.

[paesan]

The Bacon??? Nice we could call that one like "da cops" or "5-O" or "Jiggs" or "the Fuzz... you get what I'm sayin...

[Paregoric Kid]

SWIM boiled down 5% vinegar to get a stronger concentration of acetic acid. then swim turned the stove down a bit and added the vinegar to powdered hydrocodone and powdered hydromorphone. SWIM tried it sublingually, seemed much more potent than regular hydrocodone and hydromorphone, could be placebo effect or it could have really changed them into thebacon and acetylhydromorphone

[SomniGod]

definitely search the site for other Loperamide threads... there really may be someting to this!!!!



~S~

[ontario_opiophile]

I wish a good drug could be made from the reaction but I highly doubt it's possible to make anything good from loperamide. Well actually, I meant, it would be really hard to make anything desirable from loperamide. i may be wrong but I have to think that someone would have thought of this before and people would be dealing drugs made from loperamide. If you could make something really good from it, it would be amazing, and simple but I just don't think anyone could have overlooked something like this. There are tons of chemists out there and i'm sure one of them would have leaked this info out if you could make something decent out of it. I have no chemistry background and I know nothing about the acetyl-loperamide or PEPAP so I could be totally wrong and, in that case just ignore me. I really think that if you have the acetic anhydride and loperamide and pyridine you should try it and see what you get. If you experience opiate effects from it share it with all of us here that would be awesome. Imagine just going to the store to buy loperamide and going home to your acetic anhydride and pyridine and cooking up some good opiates.Great thread

[Zoop]

Yes, someone has probably though of this before, but the thing is, I mean what makes it so nobody did it before is that what you need is a source of multi-gram quantity of pure loperamide.

Lately, with the internet and chemical suppliers on the internet, I think this idea is coming around because there are now easy sources to buy chemicals off the internet.

I have read some literature on using loperamide as an analgesic. It is rather potent in the mouse hot plate test (poor mice!). So, that makes me think there is DEFINITELY something to this.

It's just not practical to do with loperamide tablets - you'd need some pure loperamide.

[Paregoric Kid]

you can get near pure loperamide from the tablets. crush them and mix them in water and use a micron filter. you can also buy pure loperamide. I don't think you'd need pure loperamide anyways though. acetic anhydride or acetyl chloride would do a much better job than acetic acid, acetyl chloride isn't a watched chemical by the way. it's not hard or impossible to make loperamide into something useful.

[Zoop]

Huh. I seem to remember reading on some website that acetyl chloride was "watched" just b/c it could be used to make H, though it probably is rarely so.

PK, do you know where one can see a list of all chems which are watched by DEA?

That would be a good reference.

Anyway, I called sciencelab.com today and they said they never did get that loperamide in.

So, my next attempt will be with ---. I bought some acetylcarbromal from them a few months ago (nice sedative hypnotic - 100g for like 40 bucks - I ended up having to throw most of the shit away b/c I was getting hooked on it and was VERY sleepy all the time, but I digress).

Though --- doesn't list loperamide on their online catalog, they have a thing where the say "if you don't see it, ask us and we can maybe get it for you." So, I'll ask. I had to make up a fictictious company name when I ordered the acetycarbromal few months ago. All they wanted was just a name, no "proof" or anything. That's what I'll do next.

Yes, I could use loperamide tablets for a source of loperamide, but they're only 2mg per. I think the O-acetylated loperamide is not a super-potent opiate. You'd need at least 30, maybe 50mgs for a good hit. So, that's a LOT of tablets. I am going to try and procure the pure chemical. :p

[Paregoric Kid]

List I chemicals: http://en.wikipedia.org/wiki/DEA_list_I_chemicals http://www.erowid.org/psychoactives/law/law_fed_list1_2000.shtml
Watched chemicals: http://www.erowid.org/psychoactives/law/law_watched_chemicals.shtml

[Zoop]

I just sent an inquiry to "DSL Chemicals" out of Shanghai, China, asking for loperamide HCl.

Let's see if I can procure this stuff from oveseas. Fucking Sigma-Alrich are dicks. They only will sell to you if you have a "company," and want proof of it too!

I made up a fictitious company name for this DSL chemicals place; hopefully over in China they aren't too concerned with whether or not it's a real company.

[Paregoric Kid]

anyone can have a company, but DO NOT bother trying to order from Sigma.

[rachamim18]

It's is actually a very intelligent question but unfortunately the answer is no. Acetylation wouldn't offer any compund worthy of anything. As you correctly stated, the key with loperamide is the bbb. Acetylation does not make a compound more adept at this, or rather it depends on the paticular compound.

[rachamim18]

Zoop: Not only are you talking in a public forum and all DRUG forums [especially the public ones] are regularly monitored by Big Bro, but you need to have a DEA import liscence for the order. It will not be filled. If by some chance there is a fly by night company that would fill it, it will almost defnitely be snagged coming in. Unlike the grey market pharmaceuticals, you are asking for federal time.

[shaunclo]

WOW, Thats something I think we all didnt know......Big Bro is watching us, NEWS FLASH: BIG BRO IS WATCHING US ALL!!! You know, even a broken watch is right 2 times a day. Rachimimi, I dont think I have read 1 post of yours that is either trying to help out or just be kind. All I hear from you is negativity. If you havnt noticed this is a drug forum where people come together to talk about using drugs (not that I do, or ever have) Big brother is watching us at all times, no matter what you do. Try being a little more constructive than desctructive. I am starting to believe Kramorph when he said that you are probably a case-worker trying to spoil everyones fun......tell me i'm wrong

[Zoop]

Rachamin, thank you for enlightening us with the pearls of wisdom from your huge and so very amazing brain.

There is no literature anywhere out there on acetylated loperamide. So, unless you did your own secret experiments, you have no idea what you're talking about. What you are correct in, however, is that loperamide all by itself will not cross the BBB. That was stated at the beginning of this thread. Everyone knows that. The idea here is esterification of the hydroxy group on loperamide, so that it becomes more lipophilic and better at crossing into the central nervous system. I have read several articles on the central opiate activity of loperamide, when administered with certain compounds that enable it to enter the CNS. These studies were done in rodents.

Many drugs become more lipophilic upon esterification of hydroxy groups present in the molecule, most notably, morphine.

As for "Big Bro," everyone is aware of that too. So, do you really think you are shocking everyone with these amazing revelations?

Loperamide, for your information is available OTC in the U.S. It is not controlled either and not subject to ANY restrictions, nor could you fairly call it "gray market" or "black market." The only way I could get in trouble with DEA or FDA with this substance would be to manufacture my own loperamide drug product and market it to the public without proper licensing, which I am not going to do. There is nothing preventing me from acquiring loperamide HCl for treatment of irritable bowel syndrome on myself. The O-acetylated loperamide is only referenced in the chemical literature ONE TIME (I have done a search on STN, CAS online and registry), in a Journal of Chromatography article back a few years ago, where it was used as an analytical standard in gas chromatographic determination of serum levels of loperamide, so there is absolutely no way that it's controlled, watched or even cared about by the DEA. If the order is not filled, the reason will be either it's back-ordered or I don't want to buy the smallest amount they're selling. I already inquired with a supplier stateside and they didn't bat an eyelid. I have bought chems for household chores from them before, so I know they weren't bullshitting me when they told me it was back-ordered and they couldn't get it in.

Dude, chill out. :chillpill Are you a narc?

[ontario_opiophile]

You guys probably won't want to hear this but I have to agree with Rachamim. I really don't think it's possible for the acetylated loperamide to have any effect other than constipation and other loperamie type effects. I'd like to try making Racemorphan or Levorphanol thatwould be interesting but I lack the chemicals and equipment. It would be cool if someone here had all the stuff to make it. Fentanyl is hard to produce but you could cut it with quinine and lactose or caffine and produce like 100grams of high quality white synthetic"heroin" type drug out of 1gram of fentanyl. I may be a bit off in the numbers but 1 gram of a fentanyl would be equivalent to 100grams of pure diamorphine. Anyways, thats not the topic so anyways, I guess we could try the experiment with the Loperamide, maybe it's possible who knows it can't hurt to try it though. I've been looking for info on loperamide analogs and haven't found anything interesting. I am interested in Acetylated methadone though. Would that make LAAM or something different and better? I wonder what we could do to alter methadone to make it into something more powerful or euphoric.

[Zoop]

If I had NOT read a bunch of medical/pharmaceutical research literature on this subject, then I would probably feel the same way, but the fact is that loperamide is an opiate mu agonist, and the ony reason it's not centrally active is that it's just not lipophilic enough. Acetylation is a commonly used "trick" to get drugs into the CNS which won't do it on their own.

I have read one article where monkeys were given massive doses of plain lopermide orally via gastric tube, over a period of weeks, and the monkeys became opiod dependent from just the loperamide, so in large doses it does something.

I have read a couple articles about the analgesic activity of loperamide in mice and rats, when the loperamide is administered in such a way so as to get it into the CNS. They used a synthetic polypeptide called "cereport" which basically will take drugs and import them across the blood brain barrier, and the effects of this combination of loperamide and cereport were not distinguishable from morphine in the animals.

The total dearth of any research on the acetylated loperamide speaks to the fact that nobody knows how this compound would work. There are lots of synthetic opiates in the meperidine "family" which share a molecular structure very much like what an O-acetylated loperamide molecule would look like, and some of these meperidine derivatives are extremely potent. This particular group of meperidine analogs are known as "reversed ester" meperidine analogs. That is what O-acetyl loperamide would be.

So, I am not convinced that it would not work, based on the musings of a couple of dope addicts - you're also outvoted, if you want to come at it from a totally democratic point of view. Most of the commenters on this thread are at least open-minded about the possibility of this new compound being a good opiate agonist.

I am, and I am definitely going to work on it. If there is a good opiate you can make easily with an OTC drug, then we need to work hard to GET IT OFF THE MARKET! Someone might get hooked on it!

Ahhh!:D

[jacky]

an anonymous opiophile about 6 months ago contacted me on the subject of loperamide...........

This person was a chronic pain sufferer. They were maintained daily on an opiate painreliever. They had however started using loperamide in high doses (over a hundred milligrams daily) to help with the pain. They were in a panic, because they could no longer afford their loperamide bill, they could only afford the standard opiates they recieved with insurance. The claim was that they already knew that a cut of the loperamide dose was going to hurt them.

I looked over a report on loperamide once. I will get a link to it. It states that three metabolites of loperamide are created after ingestion, and that the saturation levels of these metabolites and loperamide contintue to raise for some 30 hours after ingestion, and continue tapering for a measurable 72 hours.
So the quest I geuss in this case needs to be formatted to these loperamide metabolites and lopermide perhaps. do the metabolites of loperamide have similiar action? is one of them perhaps even a little lipophyllic?
I dont know.
I have taken loperamide on many occassions. and from what I percieve it only has given me energy initially, and made me more tired, it states that right on the package, that it can cause tiredness ya know? the tiredness was a welcome addition to the many opioids and drugs that I was experimentiing with back then, I was also on a daily low DXM dose. I would take loperamide at work, and it would seem initially I would get a percievable lift from the drug after a few hours time.

And then there is the question about what loperamide does at opiate receptors THAT ARE "PEPPER' THOUGHOUT THE HUMAN BODY.
I know that the blood brain barrier exists. I think that opiate receptors all over the body may have a percievable effect on some people perhaps when theyre being stimulated or suppressed. I mean is our perception of awareness created from just our brains? Or is our WHOLE body a possible effector of our emotions/ or perception specifically of the feeling of EUPHORIA?

It is obvious that loperamide can be used to create stronger drugs, some way, but probably not a very easy nor economical way perhaps. One poster warned of the possibility of creating that opioid analog
that gives people instant parkinsons symptoms is a distinct possibility when trying to create loperamide analogs, that only those with specific chemistry knowledge should try.

So I wonder what happened with the opiophile with chronic pain that had to cut their daily loperamide use? I think they stated that it was at times up to 190 milligrams of loperamide they used daily....which may after a few days contributed to a much higher saturation level of loperamide and its metabolites in the blood.

In one study 10 people who were not opiate niave were given something like 32 milligrams of loperamide. 1 person reported mild euphoria.

Jonathan Ott states that 10% of the population feels euphoria from opiates, so opiophiles may be both blessed and cursed.
Perhaps loperamide is a drug like codeine and hydrocodone? only a small percentage of people may feel its effects culminate in a euphoric way? and some people wont feel the drug AT ALL due to insufficient levels of the enzymes needed for further metabolization of the drug into a drug that is active in the cns.

I think that anyone that may enjoy knowing just what to do with loperamide as far as creating lipophyllic analogs of it might just for public safety, keep it a secret.?

[Paregoric Kid]

the brain processes all the signals, it would be like trying to use a computer without a processor, ram, and a harddrive. the opiate receptors in the GI tract are more responsible for digestion/shitting, they do not effect the CNS and this is why loperamide doesn't work. does a small amount of loperamide cross the BBB? does some of loperamides metabolites cross the BBB? those are possible, the only thing you will get from the opioid receptors in the GI tract is a case of constipation.
yeah there is a risk, and I've mentioned it on the board before, of creating MPTP while trying to create something else from loperamide, but acetylating loperamide would not yield MPTP.

[oldschool?]

simply regarding acetic anhydryde you probably are on a watch list even for puchasing a small amount of it...considering that here in canada to buy (from a local chem supplier) in person you do have to give a name and adress and a frend of mine who bought many other chems from the place was trying to find somone else to get it for him because of the implications - i find it highly unlikly this would be the case in canada and not the usa - not to be parnoid...i am saying this from experience to be helpfull...of course they will easily sell it to you provided you give id...

[hovadagod]

Isn't it easier to just get pods and work from there?

[shaunclo]

What would have happened if Albert Hoffman kept his little "LSD" secret to himself. That would have been a great dissapointment. I think we keep coming up with great new tricks of the trade and these findings should not be kept secret. I understand the fact that some things should be kept on the DL, but we need to keep moving forward to finding the best and cheapest way of keeping us happy. Regardless of the consequences of Big Bro, or being put on a list. I myself have never been very paranoid though, I probably would have stayed out of a lot of trouble if I was though.

[hovadagod]

Opiates are way better than acid. But I just don't see how it can get much better than a strong batch of T.

[Zoop]

Here are some molecular structure diagrams to show what we're talking about.


First, the drug "PEPAP" - short for 1-(2-Phenethyl)-4-phenyl-4-acetoxypiperidine - can be viewed at http://chem.sis.nlm.nih.gov/chemidplus/chemidheavy.jsp (just type in the name "PEPAP" and hit "search").


Second, the drug "MPPP" - short for 1-Methyl-4-phenyl-4-propionoxypiperidine - can be viewed at the same website - search "MPPP"

Third, the subject of this thread, loperamide - the structure of which can be viewed there too (type in "loperamide")


See that hydroxy group on loperamide beggging to be acylated with something. MPPP is supposedly a LOT stronger than ol' meperidine, and PEPAP I am not sure, but I think it's at least as potent as meperidine.

For reference, the structure of meperidine, aka "demerol" can be viewed at ChemIDplus also (type in "meperidine").

See how the ester group in meperidine is oriented the opposite way as it is in MPPP and PEPAP? The loperamide acetic acid ester would be like those other opiates, "reversed ester" meperidine analogs.

I think it would be relatively potent, but I don't know.

I am bound and determined to procure some pure loperamide, about five grams of it, for experimenation.

PK is right, there is no risk of forming the neurotoxic Parkinson dis. inducing compound MPTP upon acylation of loperamide. MPTP forms from a different reaction in the synthesis of other meperidine analogs, most notably "MPPP" (not to be confused with "MPTP").

I tried to put those structures in as hypertext links, but when I clicked on them, it cam up as "error" so you'll have to visit the site and enter the name of the substance. ChemIDplus is an awesome resource - thanks NIH!


I have been diagnosed as being schizophrenic, with an overlay of mania.

[Paregoric Kid]

Opiates are way better than acid. But I just don't see how it can get much better than a strong batch of T.
many opioids are stronger than poppy seed/pod tea

[hovadagod]

Whenever tea is not good enough...drink more. I understand that many sythetics are stronger but I've never gotten to the point where I needed it. But loperamide is the best thingfor detox...cheapest detox med around....doctors would be prescribing it if it weren't available OTC but hey, docs need money too right? I've heard that if you drink enough T it feels like long acting H.

[Paregoric Kid]

Whenever tea is not good enough...drink more. I understand that many sythetics are stronger but I've never gotten to the point where I needed it. But loperamide is the best thingfor detox...cheapest detox med around....doctors would be prescribing it if it weren't available OTC but hey, docs need money too right? I've heard that if you drink enough T it feels like long acting H.
what do pods have to do with this thread at all? pods are illegal, o-acetyl-loperamide is not illegal. there are many opioids stronger and better than tea, pehaps you don't have a tolerance and that isn't an issue for you.

[regis]

i just want to second hovadagod said. loperamide is a GREAT detox med. i use it basically as someone would use methadone. there have been some posts over at the porg, where someone was doing a "study" and included a few of their friends IIRC. the doses i use are around that 100 mg mark- i usually use 96 mg for the first few days then cut down to 72 or 48 mg for the maintenence period. it works great. it is my lifesaver, no joking about that. i ended up finding how well it worked one weekend when i was really sick, no prospect of refil of the drogen for days and days. i was sick enough that i even called a methadone clinic a few times with weird, frantic messages. i'm sure they get lots like that. but cuz the runs were so bad, i went and got some loperamide, and over a few hours ended up taking 18 pills. and i napped. i woke up feeling normal. i was confused, let me tell you that. i wasn't high, but i was right baffled that i wasn't sick anymore.

then i figured out it was the loperamide. i was so happy, basically high on joy (on life?) and was able to eat. i went and ordered some chinese food and ate it up. took a shower (which i hate doing when sick) and even hung out with some friends. i called the done clinic and said "nevermind, i found what i needed online!" (i was pretending to do a research paper for school in my previous calls)

the first time i did it, i had bad constipation. but since, on repeated trials of this lil experiment, i haven't had those problems. every morning, i take a shit. then i dose around 8-10 am. then i don't shit the rest of the day. wash, rinse, repeat. i am able to indefinately maintain on nothing but loperamide. no valium, benadryl, whatever. just loperamide, and big doses of it. it, for me, is seriously a miracle drug, because it is a methadone-like maintnence therapy, but it doesn't tie me to a clinic and it is a TON cheaper than methadone would be. like $2-5 a day, which isn't too bad.

the trick with the immodium diet (what i call it here) is that if you go from dose to immodium it doesn't take effect right away. that is, for me it goes like this:

day 0: regular high-producing oral tea dose at 10 am.
day 1: 96 mg of immodium at 2pm. i wait until i'm a little sick. the dose doesn't make me feel 100% fine straight away, i would say i feel about 75% fine, 75% non-sick. the first night i'll sleep 6 hours usually. no diahrea, no gooseflesh, no kicking. a very slight runny nose (not much to blow out but some sniffling) and for me i get some lower back pains. none of the aching legs or hurting in your skin and bone marrow of a usual sick though. you still get the pain you get when you hit something, the hightened pain sensitivity of your skin when something scratches you, etc.
day 2: 96 mg of immodium at 8am. same as day one as far as symptoms.
day 3 or 4: this is when things get better. depending on how i felt on the previous day, i step down to 48-72 mg and i feel fine. i usually get a slight buzz, but imho, when you are dopesick feeling normal is a buzz, so i attribute it to that. also, the little bumps and bruises no longer hurt like hell, but feel like they normally would.

after this, it is smooth sailing. i usually maintain around 48 mg, but have done a taper down. the longest i've gone on nothing but immodium is two months and i had no problems. whenever i go out of town or on vacation for more than 3 days i switch to immodium. it is SO much less hassle.

LOPERAMIDE IS AN OPIATE. for those who don't comprehend, repeat that til you do. as a result, the dose you need of loperamide for maintnence is dependent on your dose of other opiate. the 96 mg is what i take when i'm using anywhere between one cup to three cups of pod grounds. the first 3 days are rougher when i'm as high as 3 cups of grounds for tea, but it still makes me feel SO much better than without it.

i don't pretend to know what is going on, but loperamide works. from the literature i've read, it isn't that loperamide CAN'T cross the BBB, rather it is pumped back across it. i don't know if by taking it for a few days in a row my BBB starts to gain affinity in some way and lets more of it pass. loperamide, when injected into the brain, is a really, really strong opiate. i am by no means achieving the full effect at that dose. but something is getting across.

the other weird and possibly diagnostic tidbit of info is that when i was sick for a couple days and then tried loperamide it worked right away. i only have to wait a few days when i'm going from tea to loperamide within 24-36 hours. i don't know why, but that's what happens.

i usually go on loperamide on purpose once every couple months for 4-7 days. why, you ask? to bring down my tolerance. in an 8 day stretch of loperamide, and during that time feeling pretty darn normal, i was able to go on a camping vacation *and* bring my tea tolerance down from 3 cups of grounds to a half a cup, which is almost my 'virgin' dose. i was pretty surprised when all i needed was half a cup again! so now i do it on purpose, usually 4 days on the loperamide halves my tolerance. even better is that is also has a huge, perhaps bigger, effect on the other aspect of tolerance- how long the dose lasts. that is, if, by habituation, i came to need two tea doses, one at 8 am and one at 6 pm, going on the loperamide for a couple days resets things back to the original 24+ dose cycle that tea has for me. that is a huge money saver :P let me tell ya.

whoever injected the loperamide with attempted acytalization and felt something ... you were prolly just feeling the loperamide man. nothing more, nothing less.

[exitwound]

One of the earlier posts said that a poster's friend, suffering chronic pain, used large frequent doses of Loperamide to boost their prescribed meds. Has anyone else got any information on this topic?

While its uses for detox are widely known, I'm curious about its uses alongside a frequent opiate regimen. Anything that can help me get more out of my prescribed & supplemental meds, I am all over it!

[bogumil]

There is a similar drug, which is used for the same purpose as loperamide. It is called Diphenoxylate (http://forum.opiophile.org/showthread.php?t=1328). It crosses the bbb. Not in large amounts but at least partly. Because of this it is sold only together with atropine. To get Diphenoxylate (http://forum.opiophile.org/showthread.php?t=1328) in a pure form should be no problem, since getting rid of the atropin shouldnt be too much of a problem. Definately more difficult than cleaning Codeine pills and for sure not a simple CWE, maybe even more difficult than cleaning Ephedrine pills, but it should work. So question is:

Has anyone ever tried to acetylate this drug?

Edited: If this is offtopic, just click on the " Diphenoxylate (http://forum.opiophile.org/showthread.php?t=1328) ", there is the other topic I made about it.

[hovadagod]

I've used Loperamide and "loperamida" to detox plenty of times. Strong opiate!! I just don't see how there isn't a better starting point if you are going to play scientist. That's all.

I get that it is fun to mess around with the structure and all....just think you'd have better luck and results experimenting with T or kratom alkaloids.

I was also saying that stuff about T B/C when there is no ceiling level of an opi. then there should be no problem regarding tolerance. Loperamide is good for detox but when it comes to trying to make new, better substances, I'd stick to the ones that cross the blood-brain barrier in their natural state and go from there.

Also, diphenoxylate is very different from loperamide. If you had a large amount of diphenoxylate, I think you'd be pretty set without much work.

[Hammilton]

I wanna find out if Loperamide is possibly enjoyable. Since it's not likely we're gonna be able to find out about loperamide itself (even P-GPi's don't increase opiate effects), I want to follow the only guide who can guide me.

Is there a way to create a Acetyl-loperamide, or I dunno... 5-MeO-Loperamide, 4-HO-Loperamide Bromo-Loperamide or 2CT-Loperamide???

lol- you get my picture, I think.

So we can't make heroin from vineager, but what about Hoperoina? Can I boil loperamide in vineager or whatever and make it the great white hype?

[Papa Verine]

I wanna find out if Loperamide is possibly enjoyable. Since it's not likely we're gonna be able to find out about loperamide itself (even P-GPi's don't increase opiate effects), I want to follow the only guide who can guide me.

Is there a way to create a Acetyl-loperamide, or I dunno... 5-MeO-Loperamide, 4-HO-Loperamide Bromo-Loperamide or 2CT-Loperamide???

lol- you get my picture, I think.

So we can't make heroin from vineager, but what about Hoperoina? Can I boil loperamide in vineager or whatever and make it the great white hype?

First of all, P-gp inhibitors DO increase opiate effects. It's not enough to get anywhere near the full effect of Lop but I've done it with the right inhibitors and large doses of Lop.

I've also wondered how difficult it would be to alter this drug and make a useful opioid. I just don't have enough chemistry knowledge to even know where to begin. Maybe one of the chemists here can chime in and see how likely they think this would be to work.

[roxi*stardust]

First of all, P-gp inhibitors DO increase opiate effects. It's not enough to get anywhere near the full effect of Lop but I've done it with the right inhibitors and large doses of Lop.

I've also wondered how difficult it would be to alter this drug and make a useful opioid. I just don't have enough chemistry knowledge to even know where to begin. Maybe one of the chemists here can chime in and see how likely they think this would be to work.
Chemists where are you guys? Interested in hearing if this is remotely possible. Just bought a bottle of 48 lopermide tablets for 3 dollars at one of the Family Dollar/Dollar General type stores.

[Hammilton]

Well, if you're saying P-GPi's will give Loperamide opiate-like effects, you either know something the authors of the studies don't, or you're speaking about opiates in general. That much'd be true. These studies were using very large doses of Loperamide (specially the one with AIDS patients- since they're taking P-GPi's in large quantities, and often have diarhea as a side effect, and also are frequently past drug abusers)- with doses topping 100mg. That's one hell of a dose.

Just because Loperamide is able to get into the brain doesn't mean it's gonna do anything enjoyable just because it's there. There are lots of mu-agonists that have no discernable narcotic effects. All the agonist-antagonists, come to mind, along with dozens of herbals.

[robojunkie]

I think Janssen, lovely makers/discoverers of the fentanyls, who also originally made loperamide also acylated it as well (or it could have been someone else later) but I believe it was still not able to produce real opiate effects. I read this somewhere recently but I can't recall off the top of my head where...I also don't know the roa they used so this could very well have been metabolized back to "regular" loperamide anyway. One other thing about it though, I don't know the specific procedure they used to acylate it (I think it was acetyl or propionyl or something similar) but if you look at the structure and then look at the structure of MPPP there are some rather unpleasant similarities, ie the potential for decarboxylation/dehydration to the tetrahydropyridine analogue...I have no idea how this would affect the brain in the case of dehydrated lope but it is a pseudo-opiate and if it could cross the brain in this form...who know's but not good I imagine, could be kinda like the MPTP thing. Wouldn't want to be that guinea pig!

[Paregoric Kid]

this has been covered before: Acetylation of Loperamide and Methadone http://forum.opiophile.org/showthread.php?t=929&highlight=loperamide+acetylation

it creates o-acetyl loperamide, and it is not likely that this is CNS active either.

also check:
http://www.bluelight.ru/vb/showthread.php?t=227410&highlight=loperamide+acetylation
http://www.bluelight.ru/vb/showthread.php?t=238424&highlight=loperamide+acetylation

[robojunkie]

this has been covered before: Acetylation of Loperamide and Methadone http://forum.opiophile.org/showthread.php?t=929&highlight=loperamide+acetylation

it creates o-acetyl loperamide, and it is not likely that this is CNS active either.

also check:
http://www.bluelight.ru/vb/showthread.php?t=227410&highlight=loperamide+acetylation
http://www.bluelight.ru/vb/showthread.php?t=238424&highlight=loperamide+acetylation

Yeah, sorry bout the repeat, sometimes I get mixed up when there's a thread from like year ago suddenly brought back a few posts up.

Yeah I am nearly certain its not active. I really think it has more to to with either the amide group at the biphenyl group or a combination of that and the lower lipophilicity of the hydroxyl group. But then again a lot of the fents have amide linkages but I don't know their metabolic fate. I'll try to find the study about the acetylated version not crossing the forbidden barrier and post it/send it to you but I think its inability to cross is similar to part of the reason why you can't just bang enkephalins and other peptides. I went back and reread the earlier parts of the thread (its this one) and the BL ones and saw conflicting reports about activity but I can be as sure as I can be without having done it that's its no better than plain old lope.

Also I doubt that the acylation would matter as, in the case of diphenoxylate, it is hydrolyzed (although in that case the free acid is the compound, in lope of course it would just revert to lope, "reverse" ester as someone said) to the much more lipophobic free acid diphenoxin which is the actual active principle in vivo. If I have time some time I will try to find a real definitive answer as to why it can't cross the barrier in the research literature. I have always wondered about this myself (treats withdrawal, but no "high"???) wrt to the central effects.

[Papa Verine]

Well, if you're saying P-GPi's will give Loperamide opiate-like effects, you either know something the authors of the studies don't, or you're speaking about opiates in general. That much'd be true. These studies were using very large doses of Loperamide (specially the one with AIDS patients- since they're taking P-GPi's in large quantities, and often have diarhea as a side effect, and also are frequently past drug abusers)- with doses topping 100mg. That's one hell of a dose.

Just because Loperamide is able to get into the brain doesn't mean it's gonna do anything enjoyable just because it's there. There are lots of mu-agonists that have no discernable narcotic effects. All the agonist-antagonists, come to mind, along with dozens of herbals.

Which "Studies" are you referencing here? Can you attach a link?

[hovadagod]

The detox capabilities are not really widely known. They are kept on the DL, most likely to keep meth clinics and bupe and the whole business of addiction treatment going strong.

[suboxoneeater]

DUDE. TOTALLY. I have pondered the same question. I think what you'd get if you make O-acetyl loperamide is a pretty good opiate agonist with central nervous system activity. There is a drug that goes by the acronym PEPAP, which is very similar to what O-acteyl loperamide would look like, except stripped-down. PEPAP briefly was sold as a designer drug back in the 80's.

Anyway, I posted something about this on this forum a little while back - I can't remember what the initial thread was...

If you are going to make O-acetyl loperamide, you HAVE TO have either acetic anhydride or acetyl chloride, both are "watched" as they can be used to make heroin. I have purchased acetic anhydride from a company called "---" out of ---. I am pretty sure DEA only monitors large amounts of acetic anhydride being bought and sold. You can get 120ml of acetic anhydride from --- for about 30 bucks + shipping. You don't need much. I highly recommend ---.com - they don't ask no questions about nothing. Great for hobbyists like us.

Well, this company "---com" sells pure loperamide HCl too! I ordered some and was told that it's on back-order with an overseas manufacturer (probably in Asia). This was back in June. I waited and waited and finally cancelled my order for the loperamide, but the past few days I have been meaning to call them up and ask if they ever got it in.

I was going to tell them that I was treating irritable bowel syndrome (IBS) with the loperamide and it's drastically cheaper if I just buy it in bulk pure form rather than piddly little 2mg tablets, because the dosages for IBS treatment are on the order of like 14mg - seven tablets of Immodium.

Well, the reaction would be extremely simple, just mix the loperamide powder with straight acetic anhydride. A small amount of pyridine is needed in the mix if you really want FULL acetylation. Pyridine's not watched, and --- sells it too.

I have tried reaction of acetic anhydride with pulverized Immodium AD tablets and was able to get a product. I did a couple big rails of it and I think I could barely feel some type of opiate effect.

O-acetyl loperamide I think would need to be about 25-50mg to be a good hit.

This is absolutely intriguiging and I think it may be the next big thing if a reliable source of pure loperamide becomes available.

But to answer your question, YES, you'd get a "drug" from acetyation of loperamide. I am almost 100% certain of that.

You should buy some polysorbate 80 and try your acetylized version with it.

[Hammilton]

Both studies are in the Journal of Psychoactive Drugs, no on the link. I'll try to get back to the library in the next few days to get the exact info.