Yerkes National Primate Research Center, Emory University, 954 Gatewood Rd NE, Atlanta, GA, 30329, USA.
Neuropsychopharmacology Research Unit, Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
Psychopharmacology (Berl). 2018 Feb;235(2):377-392. doi: 10.1007/s00213-017-4812-5. Epub 2017 Dec 16.
The use of (±)-3,4-methylenedioxymethamphetamine ((±)-MDMA) as an adjunct to psychotherapy in the treatment of psychiatric and behavioral disorders dates back over 50 years. Only in recent years have controlled and peer-reviewed preclinical and clinical studies lent support to (±)-MDMA's hypothesized clinical utility. However, the clinical utility of (±)-MDMA is potentially mitigated by a range of demonstrated adverse effects. One potential solution could lie in the individual S(+) and R(-) enantiomers that comprise (±)-MDMA. Individual enantiomers of racemic compounds have been employed in psychiatry to improve a drug's therapeutic index. Although no research has explored the individual effects of either S(+)-MDMA or R(-)-MDMA in humans in a controlled manner, preclinical research has examined similarities and differences between the two molecules and the racemic compound. This review addresses information related to the pharmacodynamics, neurotoxicity, physiological effects, and behavioral effects of S(+)-MDMA and R(-)-MDMA that might guide preclinical and clinical research. The current preclinical evidence suggests that R(-)-MDMA may provide an improved therapeutic index, maintaining the therapeutic effects of (±)-MDMA with a reduced side effect profile, and that future investigations should investigate the therapeutic potential of R(-)-MDMA.
（±）-3,4-亚甲二氧基甲基苯丙胺（（±）-MDMA）作为心理治疗的辅助手段，用于治疗精神和行为障碍，这一应用可以追溯到 50 多年前。直到最近几年，经过对照和同行评审的临床前和临床研究才为（±）-MDMA 的假设临床应用提供了支持。然而，（±）-MDMA 的临床应用受到一系列已证实的不良影响的限制。一个潜在的解决方案可能在于（±）-MDMA 所包含的单个 S(+)和 R(-)对映异构体。立体化合物的单个对映异构体已被用于精神病学，以提高药物的治疗指数。尽管没有研究以对照的方式探索 S(+)-MDMA 或 R(-)-MDMA 对人类的单独作用，但临床前研究已经检查了这两种分子和外消旋化合物之间的相似之处和差异。这篇综述讨论了与 S(+)-MDMA 和 R(-)-MDMA 的药效学、神经毒性、生理效应和行为效应相关的信息，这些信息可能为临床前和临床研究提供指导。目前的临床前证据表明，R(-)-MDMA 可能提供更好的治疗指数，在降低副作用的同时保持（±）-MDMA 的治疗效果，未来的研究应该调查 R(-)-MDMA 的治疗潜力。
