3,4-Methylenedioxymethamphetamine (MDMA): Stereoselective interactions at brain 5-HT1and 5-HT2receptors

✍ Scribed by Robert A. Lyon; Richard A. Glennon; Milt Titeler

• Book ID: 104652730
• Publisher: Springer
• Year: 1986
• Tongue: English
• Weight: 221 KB
• Volume: 88
• Category: Article
• ISSN: 0033-3158
• DOI: 10.1007/bf00178519

✦ Synopsis

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.