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View Full Version : A New Chance To Try And Feel Immodium?



Paregoric Kid
08-15-2007, 08:44 AM
hey I was wondering now that methylnaltrexone is (and possibly other similar drugs are) coming out soon I was wondering what would happen if you took a peripheral acting opiate antagonist that had a higher binding affinity than loperamide first and then took a shit load of loperamide (and depending on the half life of the antagonist redosing with it). now I don't know the binding affinity info for either methylnaltrexone or loperamide but what do you guys think, would it be an experiment worthy of trying?
in case you didn't know methylnaltrexone and peripheral acting opiate antagonists are like the opposite of immodium they are designed to knock agonists off the opiate receptors in your GI tract to PREVENT constipation from opiates.

Synack
08-16-2007, 01:58 AM
Give it a shot, but let me know first so I can purchase all the loperamide in a 5 count radius..heh

pharmboy
08-16-2007, 03:53 AM
Im not getting near anything with the
word Naltrexone in it.Methyl or not.

GOLD N DIEMONDS
08-16-2007, 04:23 AM
still need the loperamide to cross the BBB. just because there is a shit load of it floating around with no place to go doesn't mean that is going to happen.

Paregoric Kid
08-16-2007, 07:10 AM
pharmboy don't be ignorant, METHYLnaltrexone does not cross the BBB so it will not effect the receptors in your brain! this is why it is called a peripheral opiate antagonist, it doesn't effect the receptors in the central nervous system just the ones in the GI tract.
well I've heard that when taking large doses of loperamide some do slip through the BBB and if you took something like quinine or quinidine that would help it cross.

flipside
08-16-2007, 08:30 AM
Ketaconozole will help get it across the BBB PG

There is a large thread here about it.

I've used it with sucess as has Jacky and a few others.

Z-man
08-16-2007, 03:13 PM
pharmboy don't be ignorant, METHYLnaltrexone does not cross the BBB so it will not effect the receptors in your brain! this is why it is called a peripheral opiate antagonist, it doesn't effect the receptors in the central nervous system just the ones in the GI tract.
well I've heard that when taking large doses of loperamide some do slip through the BBB and if you took something like quinine or quinidine that would help it cross.

Yep, it appears that Methylnaltrexone won't put you into withdrawal, although it will probably put you in the bathroom...

But might not the quinine/quinidine change that? After all, if it helps the loperamide cross the BBB, won't it do the same for the MNTX? Seems to me like you'd be taking a bit of a risk for precious little reward.

betmylife
08-16-2007, 03:36 PM
isn't lopermide related to meperdine? sounds like you would have to go through alot of trouble just to take some demerol....which last time I checked was about as much as immudium on the street..

Paregoric Kid
08-16-2007, 08:14 PM
loperamide is structurally related to meperidine, they are both phenylpiperidines, but that doesn't mean it is similar in strength to it. by your logic that is like saying codeine is the same strength as morphine or darvon is the same strength as methadone just because they share a structural similarity.

the reason I think it isn't a bad idea is because I've read that taking huge doses of loperamide does achieve some results and with something like methylnaltrexone you could try that and not have to worry about shitting rocks for a year. I have to read more about this, there is more to loperamide getting through the BBB than meets the eye.

pharmboy
08-16-2007, 08:43 PM
I just dont like THAT word. Gives me the
Willies.:confused:

jacky
08-24-2007, 01:12 AM
nah, I havnt used any pharms to potentiate loperamide...tried quercetin, but that was about it...
I am quite interested in which pharms could be used to make loperamide readily avialable to the brain, but havnt gone there quite yet.

...
anyway...

Synack
08-24-2007, 03:04 AM
Note: I've only started studying organic chemistry over the last three nights for a few hours and have been nodding off in between so this may ALL BE WRONG, or bits and pieces and may fubar'd

PK, from my very limited research on methylnaltrexone it appears to only remove the unwanted side effects that are created from outside of the BBB, with only peripheral action and not central action like needed to pass the BBB. I may be barking up the wrong tree here as far as understanding this correctly - but it seems cranial action could also break through the BBB, Do you know if this is true? Some 'scientists'/'chemists' are also trying to get past the BBB for treatment of brain tumors, and brain related disorders. Perhaps we could look at some of what they're doing until to get additional idea's and even brainstorm a few things.

It looks like the simplest way would be to make our weaker opiates lipid soluble, just to test it out - but I'm not sure what effect the fatty tissue would have on the absorption of the opiate. Could you look into Lipid Signaling (http://en.wikipedia.org/wiki/Lipid_signaling) as a possible answer in order to activate the correct receptors instead of passing the BBB, it's self? (if what I'm understanding is true, these "lipid signals" (http://en.wikipedia.org/wiki/Signal_transduction#Signaling_Molecules) are located outside of the BBB and signal the brain to "hit the on switch" and work it's magic.

From what I understand, we would need to find a way to get the opiates past the endothelial cells tight junctions in the brain, or something pretty similar. Can you verify this so I understand if I'm on the correct track?

I also believe that it's oxidative stress which can cause damage to the BBB, which from what I glanced at involves reactive oxygen molecules which are very small(small enough to fit through the tight junctions?) - but are very unstable.

God Speed Gentlemen :p (always wanted to say that)

Thanks and let's get to thinking, even if it's wrong and demented - cover all the bases and narrow down the current possibilities.


p.s. Feel free to delete this post if it's complete bullshit and adds nothing to this conversation :)

GOLD N DIEMONDS
08-24-2007, 03:37 AM
Yes Keep at it P.KID, you can crack the code!
wouldn't it be great/funny if it was just the addition of some real common, but strange household item

robojunkie
08-24-2007, 06:09 AM
Personally I think all this fascination with loperamide/BBB is like trying to find a way to extract that last few bits of corn out of a 50 pound pile of shit when you have a cornfield in your back yard. There are so many good opiates that are powerful and known to be of top quality. Loperamide promises at best a potent demerol derivative, and not to mention a "reverse ester" derivative (of the same configuration as the infamous MPPP, the reverse ester of meperidine that in unskilled hands of wannabe chemists can lead to MPTP which leads to MPP+ in the brain and fries an entire region of the brain leading to instant Parkinson's). I mean even if this shit did work in a "loperamide for the masses" way, off it'll go to schedule V or maybe even III, just like PE is now (V).

All this time is better spent finding a portal to the fourth spatial dimension so you could throw a bottle of robo DM in and get out a bottle of robo levomethorphan, the codeine version levo-dromoran/levorphanol. Sorry, the idea being that you can "flip" 3-D things into their mirror image in the imaginary fourth dimension, just like you can "flip" a 2-D image in the third dimension.

Anyway for those still into the lope thing, why not just cleave that amide and esterify, and alkylate or esterify that tertiary OH? Maybe then it will have a better shot like some similar compounds...I know just esterifying the tert-OH won't do it but both of these together would make it pretty damn oily.

edhorfin
08-24-2007, 08:29 AM
Im not getting near anything with the
word Naltrexone in it.Methyl or not.

God damn you got that right...I don't even like to SAY that word..

Paregoric Kid
08-30-2007, 03:39 AM
there is a thread over on bluelight and they seem to think if loperamide crossed the bbb it could be neurotoxic or form mptp like metabolites. http://www.bluelight.ru/vb/showthread.php?t=331067
another way you could probably get it through is to acetylate it into o-acetyl loperamide

robojunkie
08-30-2007, 05:17 AM
there is a thread over on bluelight and they seem to think if loperamide crossed the bbb it could be neurotoxic or form mptp like metabolites. http://www.bluelight.ru/vb/showthread.php?t=331067
another way you could probably get it through is to acetylate it into o-acetyl loperamide

I'm pretty sure I may have posted about that once in response to one of the loperamide threads. I don't have the reference right now but someone did a study on that O-acetylated derivative and it still did not show up (don't recall if it was based on qualitative observations or biopsied tissue).

Myself, I would not wanna fuck with it. I don't know what SARs exist for the neurotoxic tetrahydropyridine derivatives. Would the N-diphenylpropyl derivative be neurotoxic? I don't know, don't know if anyone does, nor do I know if anyone knows if these could form in the brain or if it would require initial -----PTP formation.

Hammilton
09-03-2007, 01:52 PM
I dunno if an o-acetylated version will even be able to get around the PGP issue.

And like it's been said before, considering the close similarity to the neurotoxic tetrahydropyridines, I think trying to get it into the brain is awfully dangerous at best.

The toxicity that's been shown makes me really fucking leary of using this stuff at all. Young children, who have incomplete BBB's are probably the most important cases to look at regarding this.

Indy
09-09-2007, 04:07 AM
I've been interested in the 'lope for years now, as its almost like when i'm in w/d's i can feel it doing something, really really helps with w/d's for me. I remember before i even joined reading about paregoric kid talking about experimenting with acetylating loperamide. Anyways, i don't think loperamide if unacetylated is dangerous in the brain, since they say in young children it causes a morphine-like high. This means it's GETTING into the brain if they're getting the high, and if its in their brain and they dont die then it's not dangerous, right? However, i'm guessing you guys were talking about it being dangerous when acetylated?

Hammilton
09-16-2007, 04:37 PM
Loperamide has a lot in common with known dopa-toxic drugs, like MPP+, Haloperidol (and quite a few other old shool anti-psychotics).

It's not known how much gets through in children, if it does (children aren't real great at explaining psychoactive effects) or how much of an effect is created.

If it is a neurotoxin, it's true that it doesn't seem likely to cause immediate MPP+-style parkinson's effects. The drug hasn't been studied in children at much length. By that I mean that they haven't done studies of children taking the drug for weeks at a time the way addicts would.

Finding a legal opioid is pretty useless unless you're able to use it repeatedly- if you have to worry about developing parkinson's disease, it's not getting you further ahead than illegal drugs (ie: if you're only using occasionally you might as well be using illegal drugs occasionally).

A legal opioid that could be used all the time is already available- Nalbuphine (I got that right, right?) and tramadol.

They're both Rx only, though, which is definitely a detractor if you live in a state or municipality that criminalised posession of prescription drugs, sans prescription.

Hammilton
11-05-2007, 07:20 PM
Double checked, you could take gallons of a peripheral antagonist and you'd still not get into the brain. You'd need a strong P-gp inhibitor.

DCBA
11-06-2007, 04:20 AM
Double checked, you could take gallons of a peripheral antagonist and you'd still not get into the brain. You'd need a strong P-gp inhibitor.

But loperamide crosses the BBB alltought to some extent, or else no one would be able to feel imodium..
If you put all the loperamide out of the gut receptors by using an antagonist, more loperamide would be freed and be able to cross the BBB.

Papa Verine
11-06-2007, 05:41 AM
I'm the one who posted threads about Loperamide and Ketoconazole, quinidine and other P-gp inhibitors. I personally experimented with 200mg loading doses of ketoconazole and 50-100mg of Loperamide with positive results that ABSOLUTELY resulted in CNS opioid-like effects simlar to methadone.

But that was quite a tolerance ago and A lot of potentially dangerous drugs I don't think I want to experiment with anymore. Quinidine is associated with a number of dangerous side effects and so is ketoconazole, to a lesser degree. I don't consider Loperamide to be any more dangerous then regular methadone or meperidine use. All I had to complain about, after consuming thousands of mgs of the stuff, was nausea and constipation. The constipating effect is similar to heavy use of any opioid. In fact, I got a tolerance to the constipating effect of Loperamide and could take 20mg and be shitting regularly the next day, about 24 hours later. I did all this when I was not using opiates regularly, about a year ago today. Oh boy, how things have changed.

Paregoric Kid
11-06-2007, 05:52 AM
yeah that was the point, some slips across and if you took a huge amount then it would make sense that a dose big enough to feel would slip through, but if you tried this without a peripheral acting mu antagonist you would die from not being able to shit
and methadone is pretty safe, meperidine on the other hand can cause some nasty problems in certain situations, like seizures from it's metabolites. no one to my knowledge has tried taking loperamide for an extended period of time in a way that bypassed the BBB, so we can't be sure of how safe or dangerous it could be if it were possible.

Papa Verine
11-06-2007, 05:59 AM
You're right, it's quite possible it is very dangerous to do for an extended peroid of time. Like I said, I'm not willing to experiment with it myself anymore.

Hammilton
02-04-2008, 12:22 PM
But loperamide crosses the BBB alltought to some extent, or else no one would be able to feel imodium..
If you put all the loperamide out of the gut receptors by using an antagonist, more loperamide would be freed and be able to cross the BBB.

That's not how your body works. Loperamide molecules aren't magically drawn to the receptors, they diffuse through the body. Your blood pushes them around, and when they come in contact with a working receptor, blammo!

A peripheral mu-antagonist wouldn't do any good at all. It's not going to block receptors so that loperamide is free to go somewhere else. Loperamide won't be binding at these receptors, but what's that matter: when they bind, they release instantly. Partial agonists hold on for a while, and this isn't a partial agonist. I might agree if it was.

I don't think that a peripheral MOR-Antagonist would be needed. Eventually you'll reach saturation, and is probably reached constantly by most addicts. I dunno, though, I'd have to look into that.

Here's a little something I learned recently: Sertraline (and another SSRI, I forget which) are both P-gp inhibitors. They're a little more available for most people than quinine and ketoconazole. Unless you feel like downing foot cream or dandruff shampoo.

I think that Loperamide should be enjoyed by absolute newbs. I'd like to see what they'd say about it. By the time you learn about it here or at BL, you've already built up quite a tolerance. I should put out a handbook for every brand new drug user that says "fake depression and buy immodium"