3,4-Methylenedioxymethamphetamine (Ecstasy) Inhibits Dyskinesia Expression and Normalizes Motor Activity in 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Treated Primates
Mahmoud M. Iravani, Michael S. Jackson, Mikko Kuoppamäki, Lance A. Smith, Peter Jenner
Journal of Neuroscience October 8, 2003 DOI: 10.1523/jneurosci.23-27-09107.2003 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Common marmosets (Callithrix jacchus); one human patient with Parkinson's disease |
| Interventions | MDMA L-DOPA pramipexole fluvoxamine 5-HT1A/B antagonists |
| Topics | MDMA Serotonin |
| Keywords | Pharmacology Dopaminergic Pramipexole Levodopa Tardive dyskinesia Parkinson's disease |
| Citations | 105 |
| Key findings | MDMA reduces L-DOPA-induced dyskinesia in marmosets through serotoninergic mechanisms, suggesting serotonin receptors modulate dyskinesia. |
Abstract
Ecstasy [3,4-methylenedioxymethamphetamine (MDMA)] was shown to prolong the action of l -3,4-dihydroxyphenylalanine ( l -DOPA) while suppressing dyskinesia in a single patient with Parkinson's disease (PD). The clinical basis of this effect of MDMA is unknown but may relate to its actions on either dopaminergic or serotoninergic systems in brain. In normal, drug-naive common marmosets, MDMA administration suppressed motor activity and exploratory behavior. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated, l -DOPA-primed common marmosets, MDMA transiently relieved motor disability but over a period of 60 min worsened motor symptoms. When given in conjunction with l -DOPA, however, MDMA markedly decreased dyskinesia by reducing chorea and to a lesser extent dystonia and decreased locomotor activity to the level observed in normal animals. MDMA similarly alleviated dyskinesia induced by the selective dopamine D2/3 agonist pramipexole. The actions of MDMA appeared to be mediated through 5-HT mechanisms because its effects were fully blocked by the selective serotonin reuptake inhibitor fluvoxamine. Furthermore, the effect of MDMA on l -DOPA-induced motor activity and dyskinesia was partially inhibited by 5-HT1a/b antagonists. The ability of MDMA to inhibit dyskinesia results from its broad spectrum of action on 5-HT systems. Serotoninergic receptors appear to play an important modulatory role in l -DOPA-induced dyskinesia, and this study may provide a framework for the use of serotoninergic agents in the treatment of l -DOPA-induced dyskinesia.
Comparable studies
Other experimental studies on MDMA, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin | 2000 | Experimental study | |
| Methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA) cause selective ablation of serotonergic axon terminals in forebrain: immunocytochemical evidence for neurotoxicity Rat brain | 1988 | Experimental study | |
| The molecular mechanism of "ecstasy" [3,4-methylenedioxy-methamphetamine (MDMA)]: serotonin transporters are targets for MDMA-induced serotonin release. Human platelet plasma membrane vesicles and bovine adrenal chromaffin granule membrane... | 1992 | Laboratory study | |
| Oxytocin-dependent reopening of a social reward learning critical period with MDMA | 2019 | Experimental study | |
| Effects of certain hallucinogenic amphetamine analogs on the release of [3H]-serotonin from rat brain synaptosomes Rat whole brain synaptosomes | 1982 | Experimental study |
Citations in the library
Cited by 8
- Characterization of 3,4-Methylenedioxymethamphetamine (MDMA) EnantiomersIn Vitroand in the MPTP-Lesioned Primate:R-MDMA Reduces Severity of Dyskinesia, WhereasS-MDMA Extends Duration of ON-Time Journal of Neuroscience May 11, 2011
- MDMA and fenfluramine reduce L‐DOPA‐induced dyskinesia via indirect 5‐HT1A receptor stimulation European Journal of Neuroscience May 1, 2006
- MDMA‐evoked changes in [11C]raclopride and [11C]NMSP binding in living pig brain Synapse July 14, 2004
- Synthesis of R- and S-MDMA via nucleophilic ring-opening of homochiral N-tosylaziridines Australian Journal of Chemistry July 11, 2023
- A Systematic Review of the MDMA Model to Address Social Impairment in Autism. Current Neuropharmacology 2021
and 3 more in the library
Cites 7
- The effect of 3,4‐methylenedioxymethamphetamine (MDMA, ?ecstasy?) and its metabolites on neurohypophysial hormone release from the isolated rat hypothalamus British Journal of Pharmacology February 1, 2002
- Direct effects of 3,4‐methylenedioxymethamphetamine (MDMA) on serotonin or dopamine release and uptake in the caudate putamen, nucleus accumbens, substantia nigra pars reticulata, and the dorsal raphé nucleus slices Synapse April 27, 2000
- The pharmacology and clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy"). Pharmacological Reviews September 2003
- Arginine vasopressin release in response to the administration of 3,4-methylenedioxymethamphetamine ("ecstasy"): is metabolism a contributory factor? Journal of Pharmacy and Pharmacology October 2001
- Review of the pharmacology and clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA or "Ecstasy"). Psychopharmacology June 1995
and 2 more in the library