MDA psychopharmacology

[ungelesene_bettlek]

shulgin writes that with MDA, the R-isomer is the more potent one (like it is the case with psychedelic amphetamines like DOM), while the S-isomer is also active and being more similar to MDMA than racemic MDA. on the other hand, for MDMA and amphetamine the S-isomer is the more potent one. shulgin also writes that there is little to none cross-tolerance between MDA and MDMA. can one conclude from that that the effects of MDA are mostly mediated by 5HT2A-agonism, while monoamine release is only a minor contribution, and that it is the other way round with MDMA?

 

[sekio]

No, I think racemic MDMA and racemic MDA will share some tolerance due to sharing activities (serotonin release)

Although, a paper showed that MDA and MDMA are not cross tolerant in rats despite the clear similarity in effects. They note that MDA substitutes for the hallucinogens LSD/DOM in drug discrimination studies but MDMA does not. Also it goes on to note the actions of MDA were opposed by a 5-HT antagonist whereas the effects of MDMA were better opposed by a norepinephrine antagonist.

Also interesting to note is that MDMA and methamphetamine showed cross tolerance.

MDA is still a good monoamine releaser - MDMA is just more of a "stimulant": more monoamine release & much less active at 5-HT2a

 

[ungelesene_bettlek]

the effects of MDMA were better opposed by a norepinephrine antagonist.

so is noradrenaline release a major factor in the effects of MDMA? or is itself an noradrenaline agonist?

MDA is still a good monoamine releaser

I guess it is reasonable to assume that R-MDA is more active as 5HT2A-agonist and S-MDA is more active as monoamine releaser?

and do psychedelic amphetamines like DOM (or more specifically their S-isomers) also act as monoamine releaser?

MDMA is just more of a "stimulant": more monoamine release & much less active at 5-HT2a

is the 5HT2A-agonist activity mediated by MDMA directly, or by MDA generated by metabolism?

 

[sekio]

Noradrenaline release is apparently a large part of MDMA's effects (explains why MDAI never really took off)

Psychedelic amphetamines like DOM do not generally cause monoamine release in the same way that the "true" amphetamines do. Conversely, N-methylated amphetamines lack affinity for 5-HT2a.

Effect of the R(-) and S(+) isomers of MDA and MDMA on phosphatidyl inositol turnover in cultured cells expressing 5-HT2A or 5-HT2C receptors.
Nash JF, Roth BL, Brodkin JD, Nichols DE, Gudelsky GA.
Neurosci Lett. 1994 Aug 15;177(1-2):111-5.

The isomers of MDA [activated] the 5-HT2A receptors, with the R(-) isomer of MDA being more potent than the S(+) at the 5-HT2A receptor. The R(-) and S(+) isomers of MDMA were significantly less efficacious at the 5-HT2A receptor as compared to MDA; S(+)MDMA had no effect. At the 5-HT2C receptor, both R(-) and S(+)MDA were equipotent at stimulating PI hydrolysis, with the S(+) isomer of MDMA being more efficacious at the 5-HT2C receptor compared with the R(-) isomer. In all cases at both the 5-HT2A and 5-HT2C receptors, the affinities of the isomers of MDMA and MDA were at least 2-3 orders of magnitude less than 5-HT.

S-(+)- MDA is more stimulatory (monoamine releaser), R(-)-MDA is more active as a hallucinogenic agent.
Likewise for MDMA, but MDMA has even less affinity for 5-HT2a.

I imagine most of the 5-HT effects are caused by direct 5HT release in both drugs. MDA shows some cross tolerance with hallucinogens, though, so I think that its experience also has to do with 5-HT2a direct activation.