α₁-Adrenergic receptors contribute to the acute effects of 3,4-methylenedioxymethamphetamine in humans
Donzelli, M., Fink, A., Grouzmann, E., Hysek, C. M., Liechti, M. E., Simmler, L. D.
This study assessed the effects of the α₁-noradrenergic receptor antagonist, doxazosin (8mg/day for 3 days), on the acute response to MDMA (125mg) in healthy subjects (n=16). Doxazosin reduced MDMA-induced elevations in blood pressure, and body temperature, and moderately attenuated positive mood but enhanced tachycardia associated with MDMA.
Abstract
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.