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Review ArticleReview

The Pharmacology and Clinical Pharmacology of 3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy”)

A. Richard Green, Annis O. Mechan, J. Martin Elliott, Esther O'Shea and M. Isabel Colado
Pharmacological Reviews September 2003, 55 (3) 463-508; DOI: https://doi.org/10.1124/pr.55.3.3
A. Richard Green
Neuropharmacology Research Centre, School of Pharmacy, De Montfort University, Leicester, United Kingdom (A.R.G., A.O.M., J.M.E.); AstraZeneca R&D Charnwood, Loughborough, United Kingdom (A.R.G.); and Departamento de Farmacologia, Facultad de Medicina, Universidad Complutense, Madrid, Spain (E.O., M.I.C.)
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Annis O. Mechan
Neuropharmacology Research Centre, School of Pharmacy, De Montfort University, Leicester, United Kingdom (A.R.G., A.O.M., J.M.E.); AstraZeneca R&D Charnwood, Loughborough, United Kingdom (A.R.G.); and Departamento de Farmacologia, Facultad de Medicina, Universidad Complutense, Madrid, Spain (E.O., M.I.C.)
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J. Martin Elliott
Neuropharmacology Research Centre, School of Pharmacy, De Montfort University, Leicester, United Kingdom (A.R.G., A.O.M., J.M.E.); AstraZeneca R&D Charnwood, Loughborough, United Kingdom (A.R.G.); and Departamento de Farmacologia, Facultad de Medicina, Universidad Complutense, Madrid, Spain (E.O., M.I.C.)
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Esther O'Shea
Neuropharmacology Research Centre, School of Pharmacy, De Montfort University, Leicester, United Kingdom (A.R.G., A.O.M., J.M.E.); AstraZeneca R&D Charnwood, Loughborough, United Kingdom (A.R.G.); and Departamento de Farmacologia, Facultad de Medicina, Universidad Complutense, Madrid, Spain (E.O., M.I.C.)
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M. Isabel Colado
Neuropharmacology Research Centre, School of Pharmacy, De Montfort University, Leicester, United Kingdom (A.R.G., A.O.M., J.M.E.); AstraZeneca R&D Charnwood, Loughborough, United Kingdom (A.R.G.); and Departamento de Farmacologia, Facultad de Medicina, Universidad Complutense, Madrid, Spain (E.O., M.I.C.)
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Abstract

The amphetamine derivative (±)-3,4-methylenedioxymethamphetamine (MDMA, ecstasy) is a popular recreational drug among young people, particularly those involved in the dance culture. MDMA produces an acute, rapid enhancement in the release of both serotonin (5-HT) and dopamine from nerve endings in the brains of experimental animals. It produces increased locomotor activity and the serotonin behavioral syndrome in rats. Crucially, it produces dose-dependent hyperthermia that is potentially fatal in rodents, primates, and humans. Some recovery of 5-HT stores can be seen within 24 h of MDMA administration. However, cerebral 5-HT concentrations then decline due to specific neurotoxic damage to 5-HT nerve endings in the forebrain. This neurodegeneration, which has been demonstrated both biochemically and histologically, lasts for months in rats and years in primates. In general, other neurotransmitters appear unaffected. In contrast, MDMA produces a selective long-term loss of dopamine nerve endings in mice. Studies on the mechanisms involved in the neurotoxicity in both rats and mice implicate the formation of tissue-damaging free radicals. Increased free radical formation may result from the further breakdown of MDMA metabolic products. Evidence for the occurrence of MDMA-induced neurotoxic damage in human users remains equivocal, although some biochemical and functional data suggest that damage may occur in the brains of heavy users. There is also some evidence for long-term physiological and psychological changes occurring in human recreational users. However, such evidence is complicated by the lack of knowledge of doses ingested and the fact that many subjects studied are or have been poly-drug users.

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Pharmacological Reviews: 55 (3)
Pharmacological Reviews
Vol. 55, Issue 3
1 Sep 2003
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Review ArticleReview

The Pharmacology and Clinical Pharmacology of 3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy”)

A. Richard Green, Annis O. Mechan, J. Martin Elliott, Esther O'Shea and M. Isabel Colado
Pharmacological Reviews September 1, 2003, 55 (3) 463-508; DOI: https://doi.org/10.1124/pr.55.3.3

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Review ArticleReview

The Pharmacology and Clinical Pharmacology of 3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy”)

A. Richard Green, Annis O. Mechan, J. Martin Elliott, Esther O'Shea and M. Isabel Colado
Pharmacological Reviews September 1, 2003, 55 (3) 463-508; DOI: https://doi.org/10.1124/pr.55.3.3
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  • Article
    • Abstract
    • I. Introduction
    • II. Epidemiological Studies on the Use of MDMA
    • III. Acute Effects of MDMA in Experimental Animals
    • IV. Long-Term Effects (Neurotoxicity) in Experimental Animals
    • V. Effects of MDMA in Humans
    • VI. Metabolism of MDMA
    • VII. Conclusions
    • Acknowledgments
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