The molecular mechanism of "ecstasy" [3,4-methylenedioxy-methamphetamine (MDMA)]: serotonin transporters are targets for MDMA-induced serotonin release.
Proceedings of the National Academy of Sciences March 1, 1992 DOI: 10.1073/pnas.89.5.1817 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Laboratory study Peer reviewed |
|---|---|
| Population | Human platelet plasma membrane vesicles and bovine adrenal chromaffin granule membrane vesicles |
| Intervention | MDMA |
| Topics | MDMA Serotonin |
| Keywords | Serotonin transporter Vesicle Pharmacology Biochemistry Efflux Biophysics |
| Citations | 533 |
| Key points | MDMA stimulates serotonin efflux from both plasma membrane and secretory vesicle transporters through distinct mechanisms involving direct transporter interaction and pH gradient dissipation. |
Abstract
MDMA ("ecstasy") has been widely reported as a drug of abuse and as a neurotoxin. This report describes the mechanism of MDMA action at serotonin transporters from plasma membranes and secretory vesicles. MDMA stimulates serotonin efflux from both types of membrane vesicle. In plasma membrane vesicles isolated from human platelets, MDMA inhibits serotonin transport and [3H]imipramine binding by direct interaction with the Na(+)-dependent serotonin transporter. MDMA stimulates radiolabel efflux from plasma membrane vesicles preloaded with [3H]serotonin in a stereo-specific, Na(+)-dependent, and imipramine-sensitive manner characteristic of transporter-mediated exchange. In membrane vesicles isolated from bovine adrenal chromaffin granules, which contain the vesicular biogenic amine transporter, MDMA inhibits ATP-dependent [3H]serotonin accumulation and stimulates efflux of previously accumulated [3H]serotonin. Stimulation of vesicular [3H]serotonin efflux is due to dissipation of the transmembrane pH difference generated by ATP hydrolysis and to direct interaction with the vesicular amine transporter.
In the evidence
This study is part of the evidence base for 2 syntheses in the library. Here is how each one recorded it.
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State of the evidence: MDMA Supports
MDMA stimulates serotonin efflux via both plasma membrane and vesicular transporters through direct transporter interaction and pH gradient dissipation.
Synthesized
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State of the evidence: Serotonin Supports
MDMA stimulates serotonin efflux by interacting directly with plasma membrane and vesicular serotonin transporters and by dissipating the vesicular pH gradient.
Synthesized
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 | |
| 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 | |
| 5-HT2 receptors exert a state-dependent regulation of dopaminergic function: studies with MDL 100,907 and the amphetamine analogue, 3,4-methylenedioxymethamphetamine | 1992 | Experimental study |
Citations in the library
Cited by 142
- MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nature Medicine June 1, 2021
- Gender differences in the subjective effects of MDMA Psychopharmacology March 5, 2001
- Small Changes in Ambient Temperature Cause Large Changes in 3,4-Methylenedioxymethamphetamine (MDMA)-Induced Serotonin Neurotoxicity and Core Body Temperature in the Rat Journal of Neuroscience July 1, 1998
- Oxytocin-dependent reopening of a social reward learning critical period with MDMA Nature April 3, 2019
- Psychedelics reopen the social reward learning critical period Nature June 14, 2023
and 137 more in the library
Cites 3
- Methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA) cause selective ablation of serotonergic axon terminals in forebrain: immunocytochemical evidence for neurotoxicity Journal of Neuroscience August 1, 1988
- Hallucinogenic Amphetamine Selectively Destroys Brain Serotonin Nerve Terminals Science September 6, 1985
- Effects of certain hallucinogenic amphetamine analogs on the release of [3H]-serotonin from rat brain synaptosomes Journal of Medicinal Chemistry May 1, 1982