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N-alphamethylbenzyl amphetamine bioassay

E

ex-amine

Bluelighter
Joined
Jan 31, 2005
Messages
152
yes your favorite hippychickie is back.

Looked at Amphetaminil and decided to take the acetonitrile off , but leave the methyl there.
Now I know what you all are thinking now :

this compound is a prodrug to amphetamine.
simple break it at the amine and you are there.

this might happen after a few rounds swirling through your hepatic and "what not" enzymatic circulations.

but before that even happens it seems to be a .....

Sigma1 agonist , known for interactions with o.a. dextromorphan , pcp , opoids , meth and more.

After reading up and down i came to this preliminary conclusion :
personally i think it will be a psuedo-opiod-effect and some time released stimulation.

but hey , it might even be a hallucinogen ,
or some worthless crap or some worthless inactive crap !

except for possible heart problems i do not see any truly toxic metabolites
(well possible metabolites might be meth , amphs and the shitty alpha-methyl-benzylamine ..(which i doubt will form)

trails til now :

1) few mg on skin , no reaction (rash) within few hours so probably not allergic to this compound.

2) taken less then 1 mg orally -
00.00 heart rate went up but could have been anticipation , same for bloodpressure.
05.00 heart rate back to normal , stuff has bad taste
15.00 feel lazier then normal , but no drug effect yet.
30.00 still baseline
8 hours later : this was a good try , nothing bad happend (or i didn't notice !)

i'll keep the tests dosages low for now because the sigma-receptor interacts with some very potent opiods , and we are not sure in what this compound does in that area.

Happy to be back
more trails to follow slowly over the coming weeks.

Kiss kiss

your Ex.
 
Last edited:
This post is nigh-illegible.

All amphetamines, esp. N-alkyl ones, interact with Sigma1. I strongly doubt this one will have action as anything out of the ordinary, it's likely comparable to benzphetamine.

Sigma receptor chemistry is messed up. It is not an opioid receptor, however, and definitely doesn't produce opioid effects... I believe agonism causes euphoria, dissociation, and in higher doses seizures and psychosis. But that's speculative given my knowledge of common ligands. (DXM, PCP, methamphetamine, cocaine, DMT, DPT)
 
There are sigma agonists that don't cause dissociation, too, though. I forget which one is usually referenced now...
 
the sigma receptor is not a receptor as people here usually understand them, it is not G protein coupled nor is it ion channel coupled
The primary function of the sigma receptor appears to be to do with chaperoning membrane components from the ER to the external cellular membrane. It binds sterols and sterol mimics, and regulates membrane fluidity and the protein composition fo the outer membrane. it is not externally located instead it is mostly on the endoplasmic reticulum and it has a lot in common structurally with some of the cytochrome P450 enzymes.
The only reason people think it is somehow associated with opioid receptors is that the benzomorphan opioids in partricular Pentazocine were the first ligands found to interact with it, as these also interact with opioid receptors it was naturally assumed that sigma 1 was some kind of opioid receptor.

many drugs of abuse are sigma-1 ligands, but it is a clear mistake to reverse the logic and say that sigma 1 ligands in particular sigma 1 agonists are necessarily drugs of abuse because they aren't.
 
I think people expect an intoxication from sigma agonists is that there are many chems that are reported to give an intoxication and these chems only known pharmacology is that they're sigma agonists. There are many examples but I think NOSCAPINE is the most popular.
 
Also several selective sigma agonists like ditolylguanidine and PRE-084 cause elevated dopamine release in limbic brain areas and are self administered in some animal models, and also seem to dampen NMDA responses so could see how the sigma agonist cough suppressants might be dissociative at higher doses. Though on the other hand known sigma agonists like igmesine or opipramol may be antidepressant, but don't seem to be recreational, and there is debate over whether the self administration of DTG or PRE-084 is truly mediated via sigma receptors, or if some other target is involved.
 
hamhurricane said:
I'm not even sure I understand what compound you are describing, is this N-benzylamphetamine or benzfetamine?
Click to expand...
I believe it's neither.
Desacetonitril would indicate N-benzylamphetamine, but the talk of "leaving the methyl there" and alpha-methylbenzylamine as a possible metabolite, leads me to believe that the OP is talking about N-(alpha-methylbenzyl)amphetamine.

An alpha-methyl on the N-benzyl should increase stability towards metabolic cleavage. Other than that, would the alpha-methyl somehow make it pharmacologically different from benzphetamine, clobenzorex and N-benzylamphetamine? I don't think so. To me it appears to be little more than a crappy prodrug for amphetamine.
 
N-(alpha-methylbenzyl)amphetamine it is.

ref for sigma1 agonism :
J.MEd. Chem 1991 , 34 .1094-1098 : Identification and exploration of the sigmaopiate Pharmacophore.

kiss kiss
 
Would you care to elaborate on why you think an alpha-methyl might significantly alter the activity - sigma agonist or other - of the N-benzylamphetamine class of compounds?

Amphetaminil, benzphetamine and clobenzorex are all weak sigma agonists. Therapeutically, they have been used in the 30-100 mg dosage range, and they're all rather plain stimulants/anorexics - not surprisingly, since they're all extensively metabolised into amphetamine (or methamphetamine, in the case of benzphetamine). Amphetamine-NBOMe and and N-benzylamphetamine are also regarded as pretty worthless. Just why did N-(alpha-methylbenzyl)amphetamine spark your interest?
 
IIRC they bred sigma knockout mice that show no special differences to their counterparts?
 
Just why did N-(alpha-methylbenzyl)amphetamine spark your interest?
Click to expand...

i ran into the freebase in our cabinet, probably to be used as an intermediate for another compound.
So made the salt just to test if it could be an active compound, that is all.
No plan behind why the methyl-moity should be more or less active.
Just pure curiosity.. (i know about the cat , that's why am carefull)

kiss kiss

Your Ex.
 
Depends who's cat.

Theory would tell, that no matter how curious he may get, or for that matter, if he is not curious at all, he is both dead and alive at the same time.

More modern theory would have curiosity superimposed over complete indifference, with a variety of transition states inbetween, thus leaving only the probability of the cats being halfway between dead or alive at any one time,.
 
me , my cat and i are in a constant flux of maybe.
at 2 mg this substance gives a numb tongue , a bit like benzocaine

still no noticable effects.

your ex.
 
Benzphetamine (Didrex) is dosed at 50mg a unit so you're really low on the dose scale.

The "numbing" is likely vasoconstriction.
 
10 mg gave me numbefied hands and an anestetic tongue again ,
for me this doesn't feel good.

will give this compound one more chance next week at the same dose.

just to see if it wasn't a reaction to something else.

kiss kiss

your Ex
 
des-acetonitrile amphetaminil is just benzphetamine, looking at the structure. Odd way to name it isn't it hippychickie? I can't say as I would be too happy putting amphetaminil itself into me, its metabolised to benzphetamine in vivo...does it get converted to both benzphetamine and acetonitrile? or is the acetonitrile immediately metabolised during the process to something else? as acetonitrile, albeit slowly, is broken down to release the cyanide ion (in cases of exposure to a spill of acetonitrile, or accidental/attempted suicidal ingestion it has been known to cause delayed cyanide toxicity, although its much less dangerous than HCN, or simple ionic cyanide salts given how slowly it releases its cyanide content, giving the body time to break it down, I would imagine its pretty bad news in the long run, if released from a med taken regularly)



The tingling and numbness sounds like vasoconstriction. I don't know too much about the parent compound, as far as dosage goes, compared to amphetamine itself, but amphetamines and vasoconstriction go together like idi amin and long pig takeout food=D

AFAIK benzphetamine isn't too potent in comparison with regular amphetamine, and it releases the latter as a slow-releasing prodrug dosage form (I imagine amphetaminil itself acts as a cyanide-releasing prodrug to a prodrug in essence. Ick! is all I can say to that, sounds rather nasty)
 
Benzphetamine is N-benzyl-N-methyl-amphetamine, Limpet Chicken. The compound being discussed is not benzphetamine, or benzylaphetamine - it's N-(alpha-methylbenzyl)amphetamine.

I don't think amphetaminil would release appreciable amounts of cyanide. Nitriles are usually stable and would rather hydrolize to amides than pop off cyanide ions, usually. Esp. the bigger, heavier nitriles.
 
Yeah, my bad, I realised that about benzphetamine soon after I posted, but I had things to do, so I couldn't come and post/edit accordingly.


Do you think it would start crapping cyanide in vivo at all, sekio? I have my doubts as to the desirability of the stuff if it does so at all, oxygen deprivation to the brain even in small degrees cannot be a healthy thing.

Is there a general rule about the metabolic stability of nitriles in humano where the release of cyanide ion is concerned? such as, for instance, data on the correlation of possible degree a substance may release cyanide vs given molecular weight? certain nitriles definately do release cyanide, such as the example of the simplest nitrile, acetonitrile. In that particular case, it has been known to cause cyanide poisoning, in some cases delayed rather than the rapid action of simple cyanides that are immediately bioavailable, rather than being produced via metabolic degredation of a parent compound.
 
Come to think of it, amphetaminil reminds me a lot of Amygdalin, which is a known source of cyanide ions.

Usually only cyano groups in metabolically labile positions (alpha carbons of amines, alcohols, ketones) or otherwise easily ionised from their parent hydrocarbon (acetonitrile) are of siginificant toxicity.
 
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