Interaction Between Reboxetine and 3,4-Methylenedioxymethamphetamine: Pharmacodynamics (PD) and Pharmacokinetics (PK)

Abstract

MDMA releases dopamine, serotonin, and norepinephrine in the brain. Serotonin uptake inhibitors have been shown to interact with 3,4-Methylenedioxymethamphetamine (MDMA) and to decrease its psychoactive and cardiovascular stimulant effects. This finding indicates that MDMA acts in part by releasing serotonin through the serotonin uptake site. However, in vitro studies show that MDMA binds more potently to the norepinephrine uptake site that to the the serotonin or dopamine uptake transporter. In addition, norepinephrine uptake site blockers such antidepressant drugs attenuate some of the behavioral effects of MDMA in animals. These preclinical data indicate that norepinephrine may also contribute to the response to MDMA in humans. To test this hypothesis this study evaluates the interacting effects of the selective norepinephrine transporter inhibitor reboxetine on the subjective and cardiovascular stimulant effects of MDMA in healthy volunteers.

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