The molecular mechanism of "ecstasy" [3,4-methylenedioxy-methamphetamine (MDMA)]: serotonin transporters are targets for MDMA-induced serotonin release - PubMed (original) (raw)

The molecular mechanism of "ecstasy" [3,4-methylenedioxy-methamphetamine (MDMA)]: serotonin transporters are targets for MDMA-induced serotonin release

G Rudnick et al. Proc Natl Acad Sci U S A. 1992.

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.

PubMed Disclaimer

Similar articles

Cited by

References

    1. J Neurosci. 1988 Aug;8(8):2788-803 - PubMed
    1. J Biol Chem. 1951 Nov;193(1):265-75 - PubMed
    1. J Med Chem. 1982 May;25(5):530-5 - PubMed
    1. J Biol Chem. 1980 Apr 25;255(8):3638-41 - PubMed
    1. Nature. 1954 Oct 9;174(4432):698 - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources