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
Philippe Huot, Tom H. Johnston, Katie D. Lewis, James B. Koprich, M. Gabriela Reyes, Susan H. Fox, Matthew Piggott, Jonathan M. Brotchie
Journal of Neuroscience May 11, 2011 DOI: 10.1523/jneurosci.1171-11.2011 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Sample size | 6 |
| Population | Female common marmosets (Callithrix jacchus) rendered parkinsonian by MPTP |
| Interventions | R-MDMA S-MDMA L-DOPA |
| Dose | 1, 3, and 10 mg/kg for R- or S-MDMA; 15 mg/kg for L-DOPA |
| Topics | MDMA |
| Keywords | Dyskinesia Hallucinogen Mptp Primate Pharmacology |
| Citations | 83 |
| Key findings | R-MDMA reduces dyskinesia severity and disabling dyskinesia duration, while S-MDMA extends ON-time but worsens dyskinesia, in MPTP-treated marmosets. |
Abstract
l -3,4-Dihydroxyphenylalanine ( l -DOPA) is the most effective treatment for Parkinson's disease, but long-term l -DOPA administration is marred by the emergence of motor complications, namely, dyskinesia and a shortening of antiparkinsonian benefit (wearing-OFF). 3,4-Methylenedioxymethamphetamine (MDMA) is unique in that it exerts antidyskinetic effects and may enhance antiparkinsonian actions of l -DOPA. MDMA is composed of two enantiomers with different pharmacological profiles; here, we describe a novel enantiospecific synthesis of the two enantiomers and expand on the previous characterization of their pharmacology. R -MDMA (rectus-MDMA) is relatively selective for 5-HT 2A receptors, whereas S -MDMA (sinister-MDMA) inhibits both serotonin (SERT) and dopamine transporters (DAT; SERT/DAT ratio of 10 to 1). R - or S -MDMA (1, 3, and 10 mg/kg, s.c.) was administered in combination with l -DOPA (15 mg/kg, s.c.) to six female common marmosets ( Callithrix jacchus ) rendered parkinsonian by MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) administration. Motor disability, including parkinsonism and dyskinesia, and duration of antiparkinsonian benefit (ON-time) were evaluated. After the administration of R -MDMA (3 and 10 mg/kg), the severity of peak-dose dyskinesia was decreased (by 33 and 46%, respectively; p < 0.05); although total ON-time was unchanged (∼220 min), the duration of ON-time with disabling dyskinesia was decreased by 90 min when compared to l -DOPA alone (69% reduction; p < 0.05). S -MDMA (1 mg/kg) increased the total ON-time by 88 min compared to l -DOPA alone (34% increase; p < 0.05), though dyskinesia were exacerbated. These data suggest that racemic MDMA exerts simultaneous effects, reducing dyskinesia and extending ON-time, by 5-HT 2A antagonism and SERT-selective mixed monoamine uptake inhibition, which arise from its R and S enantiomers, respectively.
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 18
- Psychedelic-inspired drug discovery using an engineered biosensor. Cell April 28, 2021
- Dark Classics in Chemical Neuroscience: 3,4-Methylenedioxymethamphetamine ACS Chemical Neuroscience July 12, 2018
- Illegal Drugs Laws: Clearing a 50-Year-Old Obstacle to Research PLoS Biology January 27, 2015
- Recreational drug discovery: natural products as lead structures for the synthesis of smart drugs Natural Product Reports 2014
- Separating the agony from ecstasy: R(−)-3,4-methylenedioxymethamphetamine has prosocial and therapeutic-like effects without signs of neurotoxicity in mice Neuropharmacology October 6, 2017
and 13 more in the library
Cites 5
- Methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA) cause selective ablation of serotonergic axon terminals in forebrain: immunocytochemical evidence for neurotoxicity Journal of Neuroscience August 1, 1988
- 3,4-Methylenedioxymethamphetamine (Ecstasy) Inhibits Dyskinesia Expression and Normalizes Motor Activity in 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Treated Primates Journal of Neuroscience October 8, 2003
- MDMA and fenfluramine reduce L‐DOPA‐induced dyskinesia via indirect 5‐HT1A receptor stimulation European Journal of Neuroscience May 1, 2006
- Effect of the R(-) and S(+) isomers of MDA and MDMA on phosphatidyl inositol turnover in cultured cells expressing 5-HT2A or 5-HT2C receptors. Neuroscience Letters August 1, 1994
- 3,4-Methylenedioxymethamphetamine (MDMA): stereoselective interactions at brain 5-HT1 and 5-HT2 receptors. Psychopharmacology 1986