Abstract
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.
Footnotes
This study was supported by the Swiss National Science Foundation [Grant 323230_126231]; and the Science Pool of the Department of Internal Medicine, University Hospital Basel, Basel, Switzerland.
Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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ABBREVIATIONS:
- MDMA
- 3,4-methylenedioxymethamphetamine
- AMRS
- Adjective Mood Rating Scale
- ANOVA
- analysis of variance
- AUEC
- area under the effect-time curve
- Cmax
- maximal plasma concentration
- 5D-ASC
- 5-Dimensions of Altered States of Consciousness
- DBP
- diastolic blood pressure
- Emax
- maximal effect
- HPLC
- high-performance liquid chromatography
- 5-HT
- 5-hydroxytryptamine (serotonin)
- MAP
- mean arterial pressure
- MDA
- 3,4-methylenedioxyamphetamine
- NE
- norepinephrine
- PK
- pharmacokinetic
- PD
- pharmacodynamic
- SBP
- systolic blood pressure
- STAI
- State-Trait Anxiety Inventory
- VAS
- Visual Analog Scale
- OB
- oceanic boundlessness
- AED
- anxious ego dissolution
- VR
- visionary restructuralization
- VIR
- vigilance reduction.
- Received September 26, 2011.
- Accepted October 26, 2011.
- Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics
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