3,4-Methylenedioxymethamphetamine (MDMA): Stereoselective interactions at brain 5-HT1 and 5-HT2 receptors
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- Lyon, R.A., Glennon, R.A. & Titeler, M. Psychopharmacology (1986) 88: 525. doi:10.1007/BF00178519
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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>25,000 nM in each case). The (−)>(+) 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.