Preclinical studies implicate a role for α1-noradrenergic receptors in the effects of psychostimulants, including 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”). The present study evaluated the effects of the α1-noradrenergic receptor antagonist doxazosin on the acute pharmacodynamic and pharmacokinetic response to MDMA in 16 healthy subjects. Doxazosin (8 mg/d) or placebo was administered for 3 days before MDMA (125 mg) or placebo using a randomized, double-blind, placebo-controlled, 4-session, crossover design. Doxazosin reduced MDMA-induced elevations in blood pressure, body temperature, and moderately attenuated positive mood but enhanced tachycardia associated with MDMA. The results indicate that α1-adrenergic receptors contribute to the acute cardiostimulant and to a minor extent possibly also to the thermogenic and euphoric effects of MDMA in humans.
From the *Division of Clinical Pharmacology and Toxicology, Department of Biomedicine, University Hospital Basel, University of Basel, Basel; and †Biomedicine Services, University Hospital, Lausanne, Switzerland.
Received May 30, 2012; accepted after revision December 3, 2012.
Reprints: Matthias E. Liechti, MD, MAS, Clinical Pharmacology and Toxicology, University Hospital Basel, Hebelstrasse 2, CH-4031 Basel, Switzerland (e-mail: firstname.lastname@example.org).
This work was supported by the Swiss National Science Foundation (grant 323230_126231 to M.E.L.).
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