3,4-Methylenedioxymethamphetamine (MDMA): stereoselective interactions at brain 5-HT1 and 5-HT2 receptors.
3,4-Methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxy-amphetamine (MDA), and their optical isomers, were assayed for their affinities at radiolabeled brain serotonin (5-HT1, 5-HT2) and dopamine (D2) binding sites. (R(-)-MDA and R(-)-MDMA displayed moderate affinities for 3H-ketanserin-labeled 5-HT2 sites (Ki = 3425 and 3310 nM, respectively) whereas the affinities for their S(+)-enantiomers were lower (Ki = 13,000 and 15,800 nM, respectively). Similar absolute and relative affinities were obtained at 3H-serotonin-labeled 5-HT1 sites; binding at D2 sites was very low (Ki greater than 25,000 nM in each case). The (-) greater than (+) order of potency at 5-HT2 sites is consistent with the observation that R(-)-MDA is a more potent psychoactive agent than its S(+)-enantiomer, but contrasts with the reported finding that S(+)-MDMA is more potent than R(-)-MDMA in humans. These results suggest that MDMA, unlike MDA and other hallucinogenic phenylisopropylamines, does not work primarily through a direct interaction at 5-HT sites.
Lyon
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Glennon
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Titeler
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D015104:3,4-Methylenedioxyamphetamine / Q000031:analogs & derivatives / Q000378:metabolism*; D000662:Amphetamines / Q000378:metabolism*; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D008297:Male; D008968:Molecular Conformation; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000378:metabolism*; D013329:Structure-Activity Relationship
D000662:Amphetamines; D011985:Receptors, Serotonin; D015104:3,4-Methylenedioxyamphetamine; D018817:N-Methyl-3,4-methylenedioxyamphetamine