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Thought experiment: 4-tfm-amphetamine

Skorpio

Skorpio

Sr. Moderator: N&PD, S&T
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Would this compound be neurotoxic, and would it's neurotoxicity be closer to pCa or pIa?
 
The mechanism of neurotoxicity of pCA or pIA isn't fully determined so no one can fully be sure. A scientist from Lilly investigated parahalogenated amphetamines to examine their neurotoxicity. To summarise, these compounds reduced the number of SERT that radio-labeled paroxetine could bind to, suggesting that serotonergic neurons have been killed. Administration of fluoxetine inhibited this neurotoxicity.

My thoughts are that if this compound turns out to be a strong serotonin releaser, it is likely to be neurotoxic in a similar manner, however this isn't necessarily the case.

Probably something as worrying is the possibility of the compound being a strong 5HT2b agonist (like 3-TFM-amphetamine/norfenfluramine is). This could result in cardiac fibrosis.
 
Probably something as worrying is the possibility of the compound being a strong 5HT2b agonist (like 3-TFM-amphetamine/norfenfluramine is). This could result in cardiac fibrosis.
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So are most psychedelics. Apparently not a problem with occasional use.
 
roi said:
So are most psychedelics. Apparently not a problem with occasional use.
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Where can I find a source for different 5HT2b values for various psychedelics? I was under the impression a lot of them were quite selective for 2a.
 
That's because people don't take mushrooms and DMT 24/7 for months/years.
 
Fenfluramine wad the drug that made me think of the 4-tfm version. On a related note has fenfluramine with the n ethyl replaced by a methyl been produced? If it even is close to mdma/amp/cathinone Sar, it may be really cool.

And the heart valve issue is for people taking these drugs as appetite suppressants. If you took mdma or dmt or psilocybin that often, the same would happen. (Did Shulgin have that problem? I know he had some heart valve surgery toward the end, but I'm not sure exactly what it was. )
 
Skorpio said:
Fenfluramine wad the drug that made me think of the 4-tfm version. On a related note has fenfluramine with the n ethyl replaced by a methyl been produced? If it even is close to mdma/amp/cathinone Sar, it may be really cool.

And the heart valve issue is for people taking these drugs as appetite suppressants. If you took mdma or dmt or psilocybin that often, the same would happen. (Did Shulgin have that problem? I know he had some heart valve surgery toward the end, but I'm not sure exactly what it was. )
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N-alkyl derivatives of fenfluramine probably wouldn't be all that different.
 
Do you have any reasoning why? Mdma is generally considered better than mdea. Methamphetamine is generally considered better than n-ethyl amphetamine. Mephedrone is considered better than 4 methyl ethcathinone.

Why do you say that this would not be the case with fenfluramine (3-tfm-n-ethylamphetamine) to 3-tfm-n-methylamphetamine?
 
Correct, but their affinities for different target proteins are normally within the same degree of magnitude. N-Alkyl groups aren't going to make a big difference as long as the nitrogen isn't sterically hindered, because it is likely going to be protonated and bind to a negatively charged amino acid residue.
 
The dangers (I mean multiple deaths in West Yorkshire 2 years ago) was caused by some bright-spark mixing p-TAP with amphetamine to approximate MDMA - I had to write up the paper from medical data, police data and lab-data on the compound. Someone else turned it into English and was presented to the W.Yorkshire drug squad on a training day. Michael Linnell actually took the lecture.
 
Forgive my ignorance but what as p tap?and thanks for the further explanation aced
 
Probably para-trifluoromethylamphetamine, the compound of discussion.
 
Yeah, para trifluoromethyl amino propane. I had that revelation last night on ketamine
 
Skorpio said:
Yeah, para trifluoromethyl amino propane. I had that revelation last night on ketamine
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It can't be that because the resulting compound lacks a phenyl group.

Most likely, it is p-tolylaminopropane, AKA 4-methylamphetamine.
 
Fenfluramine wad the drug that made me think of the 4-tfm version. On a related note has fenfluramine with the n ethyl replaced by a methyl been produced? If it even is close to mdma/amp/cathinone Sar, it may be really cool.
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As a matter of fact norfenfluramine is primarily responsible for fenfluramine's cardiotoxic effects, fenfluramine itself has a very low affinity to 5-HT2B receptors while its metabolite has an affinity two orders of magnitude higher (source, source). Sharing the same metabolite N-methylnorfenfluramine is certainly as cardiotoxic as fenfluramine.

Norfenfluramine & fenfluramine were found to cause lasting serotonin and tryptophan hydroxylase depletion, so I don't think you might expect 4-TFM-amphetamine to be a safe compound at all. According to this article 4-methylamphetamine has no activity as serotonin depletor, yet all reports of recreational use seem to conclude it doesn't feel healthy, if it was a nice empathogen/party drug as MDMA, you'd see a great demand for it and lots of it available as it doesn't require any exotic starting materials to make. I imagine 4-TFM-amphetamine may be no different.
 
Metabolism? p-Me good point to oxidise, not so with TFM.... or DFM... or FM....
 
^ No matter, it seems it doesn't have neurotoxic effects akin to pCA, which again might point to metabolism as a factor playing role in pCA's neurotoxicity. p-Methyl in MMA can be oxidized, so it doesn't block a metabolic pathway unlike halogens and likely trifluoromethyl group. But I wonder how exactly a halogen at para position blocks oxidation of the aromatic ring? Isn't it that the oxidase produces O2(-) species that attack the ring? I've just found out the active oxygen species is a single oxygen atom, so it's the aromatic ring that attacks it, so an electron-withdrawing group should make it less efficient. But then again meta-chloroamphetamine can be oxidized at the para position, why is pCA resistant to this metabolic pathway? Is it some steric feature in P450 that makes oxidation at C3 less likely?
 
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