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Levamisole and aminorex

lineartransform

lineartransform

Bluelighter
Joined
Mar 19, 2009
Messages
157
Levamisole is being seen as a cocaine cut more and more frequently - and my only question is why. The typical news blurb is that the levamisole cut is recreationally inactive, pharmaceutically pure, added at the source, and significantly more expensive than other cuts. Cocaine dealers do this because they are evil kingpins who enjoy killing people, and the world keeps on spinning.

But this really leads to the question - why levamisole? Higher costs, no apparent gain, and causes toxicity in end users. If you want to cut with something that does nothing, there are a lot of cheaper options.

Then I ran across this...

http://www.ingentaconnect.com/content/bsc/jvpt/2009/00000032/00000002/art00008

Beginning in 2004, the horseracing industry experienced an epidemic of drug positives for the amphetamine-like drug aminorex. Investigation of the therapeutic treatment of the horses called positive for this drug suggested that its source was from the administration of the anthelmintic levamisole.
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Is a similar mechanism possible in humans? Could this possible levamisole -> aminorex metabolic conversion have a recreational/synergestic effect in combination with cocaine?
 
Sounds more like a false positive as opposed to a metabolic transformation to aminorex.....

Not sure why its used in cocaine...
 
Agreed with Negrogesic about the false positive test. Dunno right now what the basis of the test is (antibody-based? GC-MS? ...), but due to the close structural similarity, this kind of confusion is not totally unexpected.

I would think that a synergistic (i.e. recreational effect) is out of question here.

Why it is used to cut coke? Well, ease of accessibilty, I guess.

- Murphy
 
This makes things a bit more interesting:

http://www.succeeddcp.com/sdcp_upload/Aminorex Release FINAL 3-17-07.pdf

To summarize, the laboratory results indicate that in our study ONLY the horses receiving the injectable levamisole phosphate product, either orally or intramuscularly, resulted in an Aminorex positive result. Aminorex was NOT found in the product itself, only in the urine of treated horses after administration of this product, and never in the urine of horses receiving other anthelmetic products.
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So it looks like there might be some metabolic conversion going on there, but I'm far from a vet.

The thing that bothers me is that even if there was a boatload of levamisole sitting around, I still don't see how it would be cheaper than using the standard dirt cheap cuts if both are recreationally inactive. All reports indicate that the levamisole is pharmaceutical grade and added at the source.

But if there's some synergy due to this aminorex metabolite + cocaine, you could increase the percieved potency to a point where it might actually offset the increased cost of levamisole vs (lactose/whatever).
 
We have a decent thread in DiTM Front Page going on about this topic.

It's similar to questions concerning Heroin cuts- from Quinine and Strychnine (I made a lengthy post in DC with speculation/history on these 2) to the 'Caines (Procaine, Lidocaine, Tetracaine, Cinchocaine), Inositol, etc.

The leader of the AIDS Brigade in Boston some years back went to great lengths to try and get some scientific research done on the combination of Diacetylmorphine - Procaine - Lidocaine. All of this is based on the anecdotes concerning the local Boston product they call P-Dope; while an old term and used in various regions, in Boston it is specifically in reference to a particular illicit Heroin variety, that is oily, and supposedly has different effects from regular Heroin.

So far scientists have come out with the standard 'there is no additional effect' mantra, but the anecdotes are reliable. Addicts have a history of learning physiological facts about drug use, combinations and addiction years before modern science figures it out independantly.

Same thing with Levamisole. It doesn't make sense that instead of Mannitol, or even Lidocaine, they would massively overload illicit Cocaine with an expensive veterinary drug- the article in DiTM puts it at 33% of illicit Cocaine iscut with Levamisole.
 
Let's stick a sec with the idea that the levamisole is thought to be a aminorex-like precursor. The metabolism of this compound was studied in 3 different specied here:

"Metabolic fate of levamisole in rats, dogs and monkeys."
Oyo Yakuri 1983, 26(6), pp.869-76
Journal written in Japanese
Abstract
The pharmacokinetics and metabolic fate of 14C-labeled levamisole (I) (20 mg/kg, orally) have been investigated in rats, dogs and monkeys. As detd. by quant. analyses of urinary metabolites by HPLC, unchanged drug was the main component in dogs (24% of urinary radioactivity), whereas the oxidative ring scission product, 2-thio-3-(2-carboxymethyl)-5-phenylimidazolidine [90032-34-1], was the main metabolite in rats and monkeys (20 and 62% of urinary radioactivity, resp.). As other common metabolites were another thiazole ring scission product, 2-oxo-3-(2-mercaptoethyl)-5-phenylimidazolidine [32190-33-3], and its metabolite [90032-39-6] as well as an automatic hydroxylation product of levamisole [6649-26-9] and its glucuronide [90032-40-9]. Levamisole exhibited affinity for red blood cells in vitro. Tissue accumulation of the drug was also obsd. in many tissues after repeated administration of labeled levamisole.
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The respective metabolites look like this:



None of those looks stimulant-like to me, but I admit, this is not so much my field. I still vote for the possibility that levamisole was used primarily, because it was easily available and maybe because it owns some propertiers that make it harder to detect resp. remove from cut coke. That would give the seller an economic advantage over lactose or other cutting agents. Quite a filthy method, if this is true.

- Murphy
 
Last edited:
Tchort said:
Same thing with Levamisole. It doesn't make sense that instead of Mannitol, or even Lidocaine, they would massively overload illicit Cocaine with an expensive veterinary drug- the article in DiTM puts it at 33% of illicit Cocaine iscut with Levamisole.
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In this point, you're probably wrong. Levamisol in bulk is really not that expensive! I guess that the coke is not cut with the ready prepared veterinary drug but with the bulk chemical, or not?
 
Thanks for the info Murphy - and I think his point was that levamisole was expensive relative to typical cutting agents, making it a poor choice if it is in fact as inactive as these far cheaper agents.

I found something interesting ( Aminorex and rexamino as metabolites of levamisole in the horse, http://dx.doi.org/10.1016/j.aca.2009.02.033 )

Abstract

Administration studies of levamisole in horses were carried out using two different levamisole preparations, namely, levamisole hydrochloride oral bolus and levamisole phosphate injectable solution. These preparations were analysed in detail for the presence of aminorex-like impurities. Both levamisole preparations were found to contain 1-(2-mercaptoethyl)-4-phenyl-2-imidazolidinone (I) and 4-phenyl-2-imidazolidinone (II) as degradation impurities, but neither aminorex nor rexamino was detected in these preparations. After the administration of these preparations to horses, aminorex, rexamino, in addition to levamisole and compound II, were detected in post-administration urine and plasma samples, among which compound II was found to have the longest detection time. Administration study of compound II was then performed on another horse to investigate whether it could be a metabolic precursor of aminorex and/or rexamino. However, no aminorex and rexamino was detected in the post-administration samples, suggesting that compound II was not a metabolic precursor of aminorex or rexamino. A metabolite (III) of compound II, tentatively identified to be a hydrolysis product of compound II, was observed instead.

It has been established unequivocally that the normal use of levamisole products in horses can lead to the presence of aminorex, rexamino and 4-phenyl-2-imidazolidinone (II) in their urine and blood samples. As compound II has the longest detection time, the detection of aminorex (and in some cases rexamino) in some of the official samples from racehorses can be ascribed to the use of levamisole products as long as compound II is also present as a marker. These findings should be of direct relevance to the investigation of some of the cases of aminorex detection in official doping control samples from racehorses.
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So it looks like horses definitely produce aminorex as a metabolite of levamisole - but the obvious point is that we aren't horses. :)
 
Can't remember the exact ref right now, but I've read that a metabolism similar to the one described in Oyo Yakuri-paper before was described to be possible by anaerobic microorganism from feces, too. Therefore, we don't know yet if it's the horse's metabolism or the one of the gastro-intestinal bacteria that produces the 'aminorex'.
 
Sounds like the start of a horse-piss drinking craze,considering the recent goings of the RC market...
 
If the enzymatic transformation of levamisole towards aminorex whould be elucidated, this could mean a totally new synthetic approach to aminorex from a bulk chemical. Hydrolysis of Vyvanse was yesterday, antihelminthics are the future ;)

- Murphy

Edit:
lineartransform said:
So it looks like horses definitely produce aminorex as a metabolite of levamisole - but the obvious point is that we aren't horses. :)
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Umm, why? Or better in this case: Why not? Was the metabolism of levamisole in humans studied in detail? Maybe we produce aminorex, too, but the amount is too small to be felt.
The german Wiki lists as most common sideeffects "vomiting and diarrhoea", and as far as I remember, horses can't vomit. I assume therefore, that these 'side-effects' occur in men. You would have a hard time noticing a slight stimulatory effect from low-dosed aminorex while puking...
 
I suspect levamisole has nothing to do with improving the pharmacology, I mean who wants to snort concentrated racehorse piss.

Instead it is added in the hope that it reduces the the ability of sniffer dogs to detect the coke, as the drug is well known to cause alteration in the sense of smell.
 
Umm, why? Or better in this case: Why not? Was the metabolism of levamisole in humans studied in detail? Maybe we produce aminorex, too, but the amount is too small to be felt.

The german Wiki lists as most common sideeffects "vomiting and diarrhoea", and as far as I remember, horses can't vomit. I assume therefore, that these 'side-effects' occur in men. You would have a hard time noticing a slight stimulatory effect from low-dosed aminorex while puking...
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Really those were just weasel words - it was a study on horses and I didn't want to imply that this meant 100% for sure that humans had similar metabolites, although imho it may be likely.

And levamisole affecting the sense of smell of drug dogs.... very, very, very interesting.
 
vecktor said:
I suspect levamisole has nothing to do with improving the pharmacology, I mean who wants to snort concentrated racehorse piss.
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Oh, that's definitively out of question.

IMHO, we should separate 2 different issues:

1. Was levamisole added with the intention to improve coke's pharmacology?
--> Definitively not. That's pure fiction.

2. Can levamisole used in some way to obtain aminorex?
--> Unlikely, but not impossible. As I said before, some of the metabolic transformations were observed by some bacteria, too. I wouldn't completely deny the possibility to use a cocktail made of commercially available enzymes, to imitate the transformation of levamisol. Currently, the respective enzymes are not known and the whole idea, therefore, pure speculation.


Cheers! Murphy
 
Looking at the chart murphy posted in #7, I'd say that at least the first one will be active stimulants (well, as a prodrug, if nothing else), if not the rest.
 
I found some recent mentioning of this issue in the peer-review literature. Maybe somebody with access can enlighten us:

"Letter to the Editor: The Possible Role of Levamisole in Illicit Cocaine Preparations"
Journal of Analytical Toxicology 2009, 33(9), p.620

- Murphy
 
I was just thinking the druglords may have levamisole in bulk amount lying somewhere, so they decided to use it to cut their coke and maximise their profits.
 
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