iodoamphetamine

[roi]

3,4-dichloroamphetamine mostly substitutes your neurons with nothing lol. As a SSRA it may substitute for MDMA in high doses, but most likely not MDA.

 

[serotonin2A]

As for your 3,4,5-halogenated amphetamine comment, neither one of us knows if they will substitute for mescaline or not (though we both have our hypotheses about it, though mine is tentative I would say)

I think you are discounting a huge body of scientific literature. It is well established that when mescaline binds to 5-HT2A, the 3- and 5-position methoxy groups form H-bonds with the receptor. Substituting non-H-bond accepting groups in the 3- and 5-positions is definitely known to reduce affinity.

http://pubs.acs.org/doi/abs/10.1021/jm060272y

 

[pr0d1gy]

I'm not sure if I understand what you mean. Do you mean the aromatic C-Cl bond being weaker than C-F? In my opinion that's the least important thing here. p-iodoamphetamine is less neurotoxic than p-choroamphetamine, so how would you explain this discrepancy? All halo groups withdraw electron density from the aromatic ring, so clearly that's not where the difference is. I suppose it all comes down to halo group size and C-X bond polarization and the partial charges it creates. p-methylamphetamine doesn't seem to be neurotoxic and methyl group is similar in size to chloro group, bromo and iodo are considerably bigger and their C-X bonds are less polarized.

In quite a few metal catalyzed cross coupling reactions aromatic iodides are very poor substrates, as are fluorides. Why this is the case with substrates like fluorobenzene is obvious. In the case of iodobenzenes the "softness" and size of the iodo substituent allow it to stabilize the metal involved in the redox reaction in its base oxidation state. P-fluoro makes it harder for the redox reaction that produces toxic products to react with the aromatic ring. Based on known in vitro chemistry, it's possible that the iodine molecule of p-iodoamphetamine stabilizes the metal active site in whatever enzyme catalyzes the conversion of p-haloamphetamines into toxic metabolites.

This type of chemistry occurs in some variations of the Ullmann Reaction. Maybe something similar is happening in the case of p-haloamphetamines. It seems like a plausible explanation for why p-iodo is less toxic than chloro or bromo.

 

[Dresden]

Ok so maybe I'm wrong on both counts, but it seems like an actual scientist somewhere would have tested 3,4-DCMA for possibly MDMA substituting properties.

 

[Dresden]

I know that PCA pretty much completely substitutes for MDMA in humans, so there.

 

[Solipsis]

If 4-MA is not neurotoxic then - like Dresden points out - how/why is the only info I ever got on it about acute and long lasting changes in mood and personality?

Considering effects of 4-FMA and 4-FA, I guess I can imagine PCA and similar chloroamps to be MDMA-like for sure, but that can be true while going in 5-HT2A agonist directions similarities don't apply. It's not the same ballgame, despite MDMA-like tendencies that mescaline can have.

 

[adder]

I suppose p-methylamphetamine does too, at the same time 3,4-dimethylamphetamine appears to be a nasty adrenergic/noradrenergic stimulant. After mephedrone got banned, there was 3,4-dimethylmethcathinone available for a short period of time as well, it was a major disappointment.