title: The norepinephrine transporter inhibitor reboxetine reduces stimulant effects of MDMA ("ecstasy") in humans.
abstract: This study assessed the pharmacodynamic and pharmacokinetic effects of the interaction between the selective norepinephrine (NE) transporter inhibitor reboxetine and 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") in 16 healthy subjects. The study used a double-blind, placebo-controlled crossover design. Reboxetine reduced the effects of MDMA including elevations in plasma levels of NE, increases in blood pressure and heart rate, subjective drug high, stimulation, and emotional excitation. These effects were evident despite an increase in the concentrations of MDMA and its active metabolite 3,4-methylenedioxyamphetamine (MDA) in plasma. The results demonstrate that transporter-mediated NE release has a critical role in the cardiovascular and stimulant-like effects of MDMA in humans.
authors.affiliation: Psychopharmacology Research Group, Division of Clinical Pharmacology and Toxicology, Department of Biomedicine and Department of Internal Medicine, University Hospital and University of Basel, Basel, Switzerland.
authors.forename: C M
authors.initials: CM
authors.lastname: Hysek
authors.forename: L D
authors.initials: LD
authors.lastname: Simmler
authors.forename: M
authors.initials: M
authors.lastname: Ineichen
authors.forename: E
authors.initials: E
authors.lastname: Grouzmann
authors.forename: M C
authors.initials: MC
authors.lastname: Hoener
authors.forename: R
authors.initials: R
authors.lastname: Brenneisen
authors.forename: J
authors.initials: J
authors.lastname: Huwyler
authors.forename: M E
authors.initials: ME
authors.lastname: Liechti
mesh_terms: D015104:3,4-Methylenedioxyamphetamine / Q000493:pharmacokinetics; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D006213:Hallucinogens / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D009025:Morpholines / Q000494:pharmacology*; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D009638:Norepinephrine / Q000097:blood* / Q000378:metabolism; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000077593:Reboxetine; D055815:Young Adult
chemical_list: D018759:Adrenergic Uptake Inhibitors; D006213:Hallucinogens; D009025:Morpholines; D050484:Norepinephrine Plasma Membrane Transport Proteins; D015104:3,4-Methylenedioxyamphetamine; D000077593:Reboxetine; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D009638:Norepinephrine