Psychopharmacology Research Group, Division of Clinical Pharmacology and Toxicology, Department of Biomedicine, University Hospital and University of Basel, Basel, Switzerland.
PLoS One. 2012;7(5):e36476. doi: 10.1371/journal.pone.0036476. Epub 2012 May 4.
This study assessed the effects of the serotonin (5-HT) and norepinephrine (NE) transporter inhibitor duloxetine on the effects of 3,4-methylenedioxy-methamphetamine (MDMA, ecstasy) in vitro and in 16 healthy subjects. The clinical study used a double-blind, randomized, placebo-controlled, four-session, crossover design. In vitro, duloxetine blocked the release of both 5-HT and NE by MDMA or by its metabolite 3,4-methylenedioxyamphetamine from transmitter-loaded human cells expressing the 5-HT or NE transporter. In humans, duloxetine inhibited the effects of MDMA including elevations in circulating NE, increases in blood pressure and heart rate, and the subjective drug effects. Duloxetine inhibited the pharmacodynamic response to MDMA despite an increase in duloxetine-associated elevations in plasma MDMA levels. The findings confirm the important role of MDMA-induced 5-HT and NE release in the psychotropic effects of MDMA. Duloxetine may be useful in the treatment of psychostimulant dependence.
Clinicaltrials.gov NCT00990067.
本研究评估了 5-羟色胺（5-HT）和去甲肾上腺素（NE）转运体抑制剂度洛西汀对 3,4-亚甲二氧基甲基苯丙胺（MDMA，摇头丸）在体外和 16 名健康受试者体内的影响。该临床研究采用双盲、随机、安慰剂对照、四组交叉设计。在体外，度洛西汀阻断了 MDMA 或其代谢物 3,4-亚甲二氧基苯丙胺从表达 5-HT 或 NE 转运体的递质加载的人细胞中释放 5-HT 和 NE。在人体中，度洛西汀抑制了 MDMA 的作用，包括循环 NE 的升高、血压和心率的增加以及药物的主观作用。尽管与度洛西汀相关的血浆 MDMA 水平升高，但度洛西汀抑制了 MDMA 的药效反应。这些发现证实了 MDMA 诱导的 5-HT 和 NE 释放对 MDMA 精神作用的重要作用。度洛西汀可能对治疗精神兴奋剂依赖有用。
Clinicaltrials.gov NCT00990067。
