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The molecular mechanism of "ecstasy" [3,4-methylenedioxy-methamphetamine (MDMA)]: serotonin transporters are targets for MDMA-induced serotonin release.
Open accessAbstract
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.
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Cited by
MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study
Mitchell, J. M., Bogenschutz, M., Lilienstein, A., Harrison, C., Kleiman, S., Parker-Guilbert, K., Ot’alora G., M., Garas, W., Paleos, C., Gorman, I., et al. (2021) · Nature Medicine · doi:10.1038/s41591-021-01336-3 · Cited by 1,004
Plasma membrane monoamine transporters: structure, regulation and function
Torres, G. E., Gainetdinov, R. R., & Caron, M. G. (2003) · Nature Reviews Neuroscience · doi:10.1038/nrn1008 · Cited by 939
Pierce, R. C., & Kumaresan, V. (2006) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2005.04.016 · Cited by 913
The human raphe nuclei and the serotonergic system
Hornung, J.-P. (2003) · Journal of Chemical Neuroanatomy · doi:10.1016/j.jchemneu.2003.10.002 · Cited by 742
Bengel, D., Murphy, D. L., Andrews, A. M., Wichems, C. H., Feltner, D., Heils, A., Mössner, R., Westphal, H., & Lesch, K.-P. (1998) · Molecular Pharmacology · doi:10.1124/mol.53.4.649 · Cited by 719
Metadata
- Authors
- Rudnick, G., & Wall, S. C.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1992-03
- Volume
- 89
- Issue
- 5
- Pages
- 1817-1821
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2016532705
- Cited by
- 535
- References
- 0
- FWCI
- 3.96
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: The molecular mechanism of "ecstasy" [3,4-methylenedioxy-methamphetamine (MDMA)]: serotonin transporters are targets for MDMA-induced serotonin release. https://app.cochat.ai/papers/10.1073/pnas.89.5.1817
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- Rudnick, G., & Wall, S. C. (1992). 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. https://doi.org/10.1073/pnas.89.5.1817
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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