Effects of the α₂-adrenergic agonist clonidine on the pharmacodynamics and pharmacokinetics of 3,4-methylenedioxymethamphetamine in healthy volunteers.
The mechanism of action of 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) involves the carrier-mediated and potentially vesicular release of monoamines. We assessed the effects of the sympatholytic α₂-adrenergic receptor agonist clonidine (150 μg p.o.), which inhibits the neuronal vesicular release of norepinephrine, on the cardiovascular and psychotropic response to MDMA (125 mg p.o.) in 16 healthy subjects. The study used a randomized, double-blind, placebo-controlled crossover design with four experimental sessions. The administration of clonidine 1 h before MDMA reduced the MDMA-induced increases in plasma norepinephrine concentrations and blood pressure but only to the extent that clonidine lowered norepinephrine levels and blood pressure compared with placebo. Thus, no interaction was found between the cardiovascular effects of the two drugs. Clonidine did not affect the psychotropic effects or pharmacokinetics of MDMA. The lack of an interaction of the effects of clonidine and MDMA indicates that vesicular release of norepinephrine, which is inhibited by clonidine, does not critically contribute to the effects of MDMA in humans. Although clonidine may be used in the treatment of stimulant-induced hypertensive reactions, the present findings do not support a role for α₂-adrenergic receptor agonists in the prevention of psychostimulant dependence.
Division of Clinical Pharmacology and Toxicology, Departments of Biomedicine and Internal Medicine, University Hospital and University of Basel, Basel, Switzerland.
Cédric M
CM
Hysek
Robin
R
Brugger
Linda D
LD
Simmler
Marcel
M
Bruggisser
Massimiliano
M
Donzelli
Eric
E
Grouzmann
Marius C
MC
Hoener
Matthias E
ME
Liechti
D015104:3,4-Methylenedioxyamphetamine / Q000493:pharmacokinetics; D058647:Adrenergic alpha-2 Receptor Agonists / Q000009:adverse effects / Q000494:pharmacology*; D000328:Adult; D000339:Affect / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D003000:Clonidine / Q000009:adverse effects / Q000494:pharmacology*; D003243:Consciousness / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004347:Drug Interactions / Q000502:physiology; D004644:Emotions / Q000187:drug effects; D004837:Epinephrine / Q000097:blood; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008606:Mental Processes / Q000187:drug effects; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology*; D009638:Norepinephrine / Q000097:blood; D055815:Young Adult
D058647:Adrenergic alpha-2 Receptor Agonists; D015104:3,4-Methylenedioxyamphetamine; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D003000:Clonidine; D009638:Norepinephrine; D004837:Epinephrine