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o-demethylation, then acetylation of psychedelics!

(zonk)

(zonk)

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I just had a particular thought over here...

what if you took the common method of o-demethylating common psychoactive compounds with HBr and then N-acetylating them with acetic anhydride. The advantge of this is produce new compounds that are LEGAL and still retain the parent compounds' psychoactive fx, and possibly make them more potent or atleast about the same. My ideas include:

DXM-->DXO-->"DXA"
ibogaine-->noribogaine-->"aceibogaine"
methylone-->MDHOCAT-->"acelone"(same could be done with MDMA)

obviously this rule applies to traditional opiates but for compounds with other activities i think this would be a great application. Here's my logic...

Shulgin says that for the N-hydroxylated psychedelic/empathogenic phenethylamines are essentially the sameas thier parent compounds, basically the HO on MDA(MDOH) is supposed to be a natural metabolite just as with most opiates and if I remember correctly the potency was closer to that of MDMA and somewhere between MDA and MDMA in FX. Acetylating 4-HO-tryptamines is different I believe because the acetyl is not at the N-position. So naturally this should be able to be done with methylone which is on quazi legal making a much harder to criminalize compound that is just as good.

With DXM the quite clrealy the same logical order as with it opiate other halves. DXO is proven to be more potent than DXM as an NMDA antagonist. So if codiene would be to DXM as Morphine would be to DXO then acetylating it should increase it's affinity even more making heroin is to DXA.

Even if it doesn't increase the potency in any of these it should be atleast on the same potency wise as with the 4-aco-tryptamines are to 4-ho-Ts
 
I guess those compounds would still be illegal in case of an analogue act, though it'ld provide a solution for countries without such laws.

I don't know much about psychopharmacology, so my opinion is probably worthless, but I think it sounds reasonable.
 
I think this idea/procedure would work with Ketamine aswell. K is metabolised by P450(i dont know if it's the same as with opiates:2d6/2c3)into norketamine and dehydronorketamine which are both active. I think it could quite possibly get acetylated
 
It seems pretty pointless, imho. The whole point of these drugs is to benefit the mind. A faster come up isn't important.

Besides, this doesn't help anything that's taken orally, and I don't think we need more users injecting psychedelics.
 
none of these are claimed to have a faster comeup, altho that would be nice and if these are equipotent or moreso then they shouldn't require injection. I'm hoping by acetylating they will have greater potency/duration. and be a lil more legal so they will be easier to work with
 
But a faster comeup is quite likely! Just look at the case morphine vs. heroine, the latter only being the prodrug that makes the already fast coming up of the former even more rapid.
This comparison is of course only valid, when comparing the demethylated compound with the acetylated /acylated one. The original molecule (being an ether in case of DXM and ibogaine) IS already quite lipophilic.

I can not comment about legal issues, sorry, but the whole idea should work, as long as the deacylated compounds still possess intrinsic action AND as long as you do not apply the stuff per os.

I agree with Hammilton in this case, as upon oral use the liver will strip off your ester before it reaches your brain. And I DO NOT support injection per se.
 
Wouldn't you also increase the come up speed with nasal use or vaporized? So injection isn't needed per se for it to be beneficial.
 
...ah yeah, of course you do. I just denied the use per os, that means: orally. Of course there are several other routes of application.
 
As an aside, 4-AcO-DMT has a *longer* onset duration than it's parent, 4-HO-DMT (Psilocin). This is an example of a compound where acetylation actually lengthens the onset, instead of reducing it. You're likely to see this where: ester hydrolysis may be slow due to steric hindrance (so esterases may not have good access to it, and classical hydrolysis may be slowed too), hydrolysis is required for the drug to be active, and the drug in question already has good BBB penetrability.
 
I agree with Hammilton in this case, as upon oral use the liver will strip off your ester before it reaches your brain. And I DO NOT support injection per se.
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The rectal route is the best of both worlds as long as you don't have some sort of 'it's gay' attitude as it mostly if not entirely avoids first pass metabolism, has rapid onset (not much behind IM for most drugs) yet doesn't run the risk of infected administration sites
 
the whole premise of this thread makes little sense to me, I have no idea what structure MDHOCAT would have is it methylone with the MD ring opened????

the esterases which chew phenolic acetyl esters are found in quantity in the blood, so first pass metabolism is not the only issue. T1/2 for most phenolic esters in blood is measured in minutes.

the additional consideration is that if the nitrogen becomes acetylated which in the case of 3,4 dihydroxymethcathinone, it is difficult to see how it wouldn't then there is a metabolically hard amide link here. it is not going to hydrolyse. studies on labelled and unlabelled N acetyl mescaline in humans showed a) it was inactive and b) it was mostly excreted with the amide N-acetyl group intact.
 
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I don't know how it is in other countries, but in Germany every ester of a controlled substance is controlled as well.

So since what you will get are the acetyl esters of controlled compounds they are illegal just the same at least here.


A little offtopic, but I once thought about what would happen if you acetylated opiates like oxymorphone or hydromorphone. Since oxymorphone is superior to morphine in recreational potential its acetyl ester should be superior to heroin.

I couldn't find anything about it though, maybe the problem is in synthesizing them. Just addind aceticanhydride might lead to acetylation of the 6-carbonyl-group as well, but you could transform it to a ketal as a protecting group. So it should be possible.
 
one more idea came to mind regarding this procedure but I'm not sure if it would work as i am unfamiliar with ergot related chemistry.

MethylErgonovine is a legal compound used as an oxytocic and is also the primary metabolite of Methysergide. It's reported to be hallucinogenic aswell as a related chem Ergonovine which is controlled. If it is hallucinogenic it's probly much less so than ergonovine(found in HBWR/claviceps) and carries more neg side fx and is more of a 5ht antagonist.

So perhaps adding Methergine to HBr would yeild ergonovine. I dont know if ergonovine could be acetylated tho, or if it's worth it.
 
oh and regarding the possible nausea of related lysergamide compounds like methergine,sansert,HBWR etc... I think taking a anticholinergen would fix this
 
(zonk) said:
one more idea came to mind regarding this procedure but I'm not sure if it would work as i am unfamiliar with ergot related chemistry.

MethylErgonovine is a legal compound used as an oxytocic and is also the primary metabolite of Methysergide. It's reported to be hallucinogenic aswell as a related chem Ergonovine which is controlled. If it is hallucinogenic it's probly much less so than ergonovine(found in HBWR/claviceps) and carries more neg side fx and is more of a 5ht antagonist.

So perhaps adding Methergine to HBr would yeild ergonovine. I dont know if ergonovine could be acetylated tho, or if it's worth it.
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I really think you should learn some basic chemistry. :\
 
You would have to N-protect, O-acetylate, and then N-deprotect, but N-alkyl
3,4-di-OAc-amphetamines are very likely active if IV'ed.

Disclaimer:
No one in their right mind would do that without a lot of caution. This possible new family of drugs looks more dangerous than N-alkylated 3,4-di-haloamphetamines to me even, and no one seems to want to touch them with a ten foot pole--other than the makers, prescribers, and consumers of buproprion (Wellbutrin, Zyban, etc.) that is, but with its N-tert-butyl alkyl group, it is basically pharmacologically impotent anyway. And 5-OAc-DMT is likely a one way trip to the ER or worse.
 
^ Yuck. Bufotenin Plus?

4-AcO-dialkyl-T's are fine though. Not a 5-sub'd tryptamine I ever enjoyed.

So perhaps adding Methergine to HBr would yeild ergonovine. I dont know if ergonovine could be acetylated tho, or if it's worth it.
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No, but where would you want the acetyl group and why? So you can get ergonovine into your brain quicker, and enhance the vasoconstriction it produces?
 
I actually disagree on the 5-AcO-DMT, it's probably *safer* than 5-HO-DMT for the simple reason that more of it will get into the brain rather than continue circulating in the PNS causing all it's nasty peripheral effects.
That said I still wouldn't be all that keen to have a go with it.
 
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