PMID- 22034656
OWN - NLM
STAT- MEDLINE
DCOM- 20120406
LR  - 20131121
IS  - 1521-0103 (Electronic)
IS  - 0022-3565 (Linking)
VI  - 340
IP  - 2
DP  - 2012 Feb
TI  - Effects of the alpha(2)-adrenergic agonist clonidine on the pharmacodynamics and 
      pharmacokinetics of 3,4-methylenedioxymethamphetamine in healthy volunteers.
PG  - 286-94
LID - 10.1124/jpet.111.188425 [doi]
AB  - 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 alpha(2)-adrenergic receptor agonist 
      clonidine (150 mug 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 alpha(2)-adrenergic receptor 
      agonists in the prevention of psychostimulant dependence.
FAU - Hysek, Cedric M
AU  - Hysek CM
AD  - Division of Clinical Pharmacology and Toxicology, Departments of Biomedicine and 
      Internal Medicine, University Hospital and University of Basel, Basel, 
      Switzerland.
FAU - Brugger, Robin
AU  - Brugger R
FAU - Simmler, Linda D
AU  - Simmler LD
FAU - Bruggisser, Marcel
AU  - Bruggisser M
FAU - Donzelli, Massimiliano
AU  - Donzelli M
FAU - Grouzmann, Eric
AU  - Grouzmann E
FAU - Hoener, Marius C
AU  - Hoener MC
FAU - Liechti, Matthias E
AU  - Liechti ME
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20111027
PL  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 0 (Adrenergic alpha-2 Receptor Agonists)
RN  - 4764-17-4 (3,4-Methylenedioxyamphetamine)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - MN3L5RMN02 (Clonidine)
RN  - X4W3ENH1CV (Norepinephrine)
RN  - YKH834O4BH (Epinephrine)
SB  - IM
MH  - 3,4-Methylenedioxyamphetamine/pharmacokinetics
MH  - Adrenergic alpha-2 Receptor Agonists/adverse effects/*pharmacology
MH  - Adult
MH  - Affect/drug effects
MH  - Blood Pressure/drug effects
MH  - Body Temperature/drug effects
MH  - Brain/drug effects
MH  - Clonidine/adverse effects/*pharmacology
MH  - Consciousness/drug effects
MH  - Cross-Over Studies
MH  - Double-Blind Method
MH  - Drug Interactions/physiology
MH  - Emotions/drug effects
MH  - Epinephrine/blood
MH  - Female
MH  - Heart Rate/drug effects
MH  - Humans
MH  - Male
MH  - Mental Processes/drug effects
MH  - N-Methyl-3,4-methylenedioxyamphetamine/adverse 
      effects/metabolism/*pharmacokinetics/*pharmacology
MH  - Norepinephrine/blood
MH  - Young Adult
EDAT- 2011/10/29 06:00
MHDA- 2012/04/07 06:00
CRDT- 2011/10/29 06:00
PHST- 2011/10/29 06:00 [entrez]
PHST- 2011/10/29 06:00 [pubmed]
PHST- 2012/04/07 06:00 [medline]
AID - jpet.111.188425 [pii]
AID - 10.1124/jpet.111.188425 [doi]
PST - ppublish
SO  - J Pharmacol Exp Ther. 2012 Feb;340(2):286-94. doi: 10.1124/jpet.111.188425. Epub 
      2011 Oct 27.