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Acetylation of Loperamide and Methadone

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I cant post sources because it is against forum guidelines. Bt if you live in the uk, trust me AA is sold over th internet for fux sake.
 
Some guy that I know that has done a few earners for me suggested that if you dehydrate the teriary alcohol to yield the tetrahydropyridine intermediate, followed by hydrogenation and concomitant removal of the chlorine atom then this might work. Obviously an amateur/layman would not be able to accomplish this so it is conceivable that it might possibly work.
 
Some other partial successes I've come across involve esterification with ascorbic acid to target the molecule to ascorbic acid specific uptake pumps, or covalently linking loperamide to carrier nanoparticles. Again, neither are simple single step processes, and would be near impossible to carry out in a cland. setting

Smyth said:
Some guy that I know that has done a few earners for me suggested that if you dehydrate the teriary alcohol to yield the tetrahydropyridine intermediate, followed by hydrogenation and concomitant removal of the chlorine atom then this might work. Obviously an amateur/layman would not be able to accomplish this so it is conceivable that it might possibly work.
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Yeah, Loperamide isn't inactive because it doesn't cross the BBB, it's inactive because it's a P-glycoprotein substrate. Y'all probably knew that, but I just didn't quite get the acetylation talk.
 
Has anyone gotten anyfurther than this? My friend told me about an acetylation, too. Strange coincidences ;) Even though, I don't believe, that it will be more lipophilic.
 
I don't think it can get taken much further.. my conclusions from rereading this thread are:
1) Acetylated loperamide does not make it active when taken orally
2) Acetylated loperamide *might* be active if taken rectally, but in my personal opinion it isn't
3) Acetylating loperamide has a chance of making highly toxic biproducts

There are *other* synthetic ways to make loperamide active, but they are far more complex then acetylation, and are not really worth discussing. IMHO, the secret to unlocking this molecule's activity falls with p-glycoprotein inhibitors.

Pixman said:
Has anyone gotten anyfurther than this? My friend told me about an acetylation, too. Strange coincidences ;) Even though, I don't believe, that it will be more lipophilic.
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there's a chance I could win the lottery and they are better than the chances of making highly toxic byproducts reacting GAA or acetyl chloride with loperamide lol
 
Found this from

http://forum.opiophile.org/showthread.php?t=144


I have tried "mega doses" of loperamide (like 24mg - 12 tablets) to absolutely no avail in combatting withdrawal symtpoms from my daily high-dose kratom habit.

BUT, check this out - in my work, which deals with chemical matters in the intellectual property field, chemical and pharmaceutical patents, to be specific, I have learnt a lot about the chemistry of synthetic opiates.

Also, from college course I took in pharmacology and med. chem., Org. Chem. and stuff like that. Well, loperamide is a member of the same class of drug as is meperidine (aka "demerol"), which is not a totally knock-you-on-your-ass narcotic, but it will do. I used to take so much demerol, and it would turn me into a stuttering idiot. I couldn't even say a whole sentence. It made me shaky too. Ultram, Talwin (pentazocine) and propoxyphene all do this to me too.

But, I digress. This kind of opiate that loperamide is, well some members of that class are like 100 times stronger than morphine, and waaaay stronger that meperidine.

I wish I could paste some molecular structures here and show you all what I'm talking about, but to put it simply, if loperamide is O-acetylated, like is the case with converting morphine to heroin, you can use acetic anhydride for this, I think what we would get is a REALLY strong opiate.

this O-acetyl loperamide HAS been reported in the literature but only as a standard in chromatographic determinations of serum loperamide levels. Nobody has ever investigated its biological effects.

So, in the interest of getting off, I bought 100ml of acetic anhydride from XXXX....com (they don't ask any questions, and YES you can buy acetic anhydride apparently - in small quantities - even though I've heard it's a "watched chemical"), and tried to do this conversion at home in a small labe
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I got cut off, my connection failed or something. but anyway, I tried this on about 15 immodium tablets, crushed up and mixed with a few ml of straigh acetic anhydride - what a strong vinegar smell! the whole house smell like vinegar for an hour - it dissapates quickly. I heated up the mixture over the hot plate of my coffeee maker - acetic anhydride is flammable so don't use a gas stove. Heated this stuff for a few minutes, then mixed in some 90% isopropyl alc. to kill the excess acetic anhydride, heated some more, and then put in the oven at about 120dg F to dry.

The resulting light greenish blue powder (because of the coloring from the immodium tabs) was snorted, and a slight effect was felt. It was like a very mild demerol dose.

So, I tried to find a way to order a few grams of pure loperamide to continue my experiments, with no success so far. the one supplier I mentioned before offers 5g loperamide HCl for sale on its website, and I placed and order, only to be contacted by them, saying it was permantly on "back order" from an overseas manuf.

If anyone knows more about this, please comment. I really think an extremely cheap and very potent synthetic opiate could be made from loperamide and acetic anhydride, but what is needed is a few grams or pure loperamide to start.
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Thought i'd add to this thread since i stumbled across that.
 
acetylating loperamide will not make highly toxic biproducts
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O-acetylloperamide might not be toxic, but you can still get other side reactions, such as elimination (dehydration) reactions, especially when you're talking about tertiary alcohols. That's what happened in the case of the MPPP/MPTP disaster - it was a simple, unexpected dehydration of the 1-methyl-4-phenyl-4-piperidol to MPTP that caused all those cases of severe Parkinson's disease
 
I will buy some acetic anhydride on friday and acetylate about 5 mg of pure loperamide first time and test it. Wait for report.
 
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