Division of Clinical Pharmacology and Toxicology, Department of Biomedicine and Department of Clinical Research, University Hospital Basel, Basel, Switzerland (Y.S., A.R., A.S., U.D., C.M.H., M.E.L.); and Biomedicine Service, University Hospital Lausanne, Lausanne, Switzerland (E.G.).
Division of Clinical Pharmacology and Toxicology, Department of Biomedicine and Department of Clinical Research, University Hospital Basel, Basel, Switzerland (Y.S., A.R., A.S., U.D., C.M.H., M.E.L.); and Biomedicine Service, University Hospital Lausanne, Lausanne, Switzerland (E.G.)
J Pharmacol Exp Ther. 2015 Apr;353(1):102-11. doi: 10.1124/jpet.114.222356. Epub 2015 Feb 5.
3,4-Methylenedioxymethamphetamine (MDMA; "ecstasy") is a popular recreational drug. The aim of the present study was to explore the role of dopamine in the psychotropic effects of MDMA using bupropion to inhibit the dopamine and norepinephrine transporters through which MDMA releases dopamine and norepinephrine by investigating. The pharmacodynamic and pharmacokinetic interactions between bupropion and MDMA in 16 healthy subjects were investigated using a double-blind, placebo-controlled, crossover design. Bupropion reduced the MDMA-induced elevations in plasma norepinephrine concentrations and the heart rate response to MDMA. In contrast, bupropion increased plasma MDMA concentrations and prolonged its subjective effects. Conversely, MDMA increased plasma bupropion concentrations. These results indicate a role for the transporter-mediated release of norepinephrine in the cardiostimulant effects of MDMA but do not support a modulatory role for dopamine in the mood effects of MDMA. These results also indicate that the use of MDMA during therapy with bupropion may result in higher plasma concentrations of both MDMA and bupropion and enhanced mood effects but also result in lower cardiac stimulation.
3,4-亚甲二氧基甲基苯丙胺(MDMA;“摇头丸”)是一种流行的娱乐性药物。本研究旨在通过使用安非他酮来抑制多巴胺和去甲肾上腺素转运体,从而探索多巴胺在 MDMA 致精神作用中的作用,因为 MDMA 通过该转运体释放多巴胺和去甲肾上腺素。采用双盲、安慰剂对照、交叉设计,研究了安非他酮与 MDMA 在 16 名健康受试者中的药效学和药代动力学相互作用。安非他酮降低了 MDMA 引起的血浆去甲肾上腺素浓度升高和 MDMA 引起的心率反应。相比之下,安非他酮增加了血浆 MDMA 浓度并延长了其主观作用。相反,MDMA 增加了血浆安非他酮浓度。这些结果表明,去甲肾上腺素转运体介导的释放在 MDMA 的心脏刺激作用中起作用,但不支持多巴胺在 MDMA 的情绪作用中的调节作用。这些结果还表明,在安非他酮治疗期间使用 MDMA 可能导致 MDMA 和安非他酮的血浆浓度升高和情绪作用增强,但也导致心脏刺激降低。