title: α₁-Adrenergic receptors contribute to the acute effects of 3,4-methylenedioxymethamphetamine in humans.
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.
authors.affiliation: Division of Clinical Pharmacology and Toxicology, Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.
authors.forename: Cédric M
authors.initials: CM
authors.lastname: Hysek
authors.forename: Anja E
authors.initials: AE
authors.lastname: Fink
authors.forename: Linda D
authors.initials: LD
authors.lastname: Simmler
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Donzelli
authors.forename: Eric
authors.initials: E
authors.lastname: Grouzmann
authors.forename: Matthias E
authors.initials: ME
authors.lastname: Liechti
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology*; D000328:Adult; D000339:Affect / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D017292:Doxazosin / Q000494:pharmacology*; D004347:Drug Interactions; D004837:Epinephrine / Q000097:blood; D005260:Female; D064368:Healthy Volunteers; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000493:pharmacokinetics / Q000494:pharmacology*; D009638:Norepinephrine / Q000097:blood; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects* / Q000378:metabolism; D013557:Switzerland; D055815:Young Adult
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D018340:Receptors, Adrenergic, alpha-1; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D017292:Doxazosin; D009638:Norepinephrine; D004837:Epinephrine