Selective 5-hydroxytryptamine2 receptor antagonists protect against the neurotoxicity of methylenedioxymethamphetamine in rats.
Christopher J. Schmidt, Gina M. Abbate, Christine K. Black, Vicki L. Taylor
Journal of Pharmacology and Experimental Therapeutics November 1, 1990 DOI: 10.1016/s0022-3565(25)22923-8 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experiment (preclinical study) Peer reviewed |
|---|---|
| Population | Animals (species not stated) treated with MDMA |
| Interventions | MDMA MDL 11 939 ritanserin |
| Duration | Single dose with assessment 1 week later; multiple administrations also examined |
| Topics | MDMA |
| Key findings | 5-HT2 receptor antagonists such as MDL 11,939 or ritanserin prevented MDMA-induced serotonin deficits in cortex, hippocampus, and striatum one week after a single dose, and MDL 11,939 partly reduced deficits from repeated MDMA dosing. Protection required administration within one hour of MDMA. The authors propose that 5-HT2 antagonists block neurotoxicity by interfering with the dopamine neuron's ability to maintain its cytoplasmic transmitter pool and sustain carrier-mediated dopamine release. |
Abstract
The serotonergic deficits resulting from methylenedioxymethamphetamine (MDMA)-induced neurotoxicity were prevented by the simultaneous administration of 5-hydroxytryptamine2 (5-HT2) receptor antagonists such as MDL 11,939 or ritanserin. This effect was not region specific as protection was observed in the cortex, hippocampus and striatum 1 week after the administration of a single dose of MDMA. MDL 11,939 also showed some efficacy at reducing the deficits in 5-HT concentrations and tryptophan hydroxylase activity produced by multiple administrations of MDMA. Protection against the neurotoxicity required the administration of MDL 11,939 within 1 hr of MDMA indicating 5-HT2 receptor activation was an early event in the process leading to terminal damage. Examination of the effect of the 5-HT2 receptor blockade on the early neurochemical alterations induced by MDMA revealed an inhibitory effect on MDMA-stimulated dopamine synthesis. Analysis of these data and the associated changes in dopamine metabolites indicates that 5-HT2 receptor antagonists block MDMA-induced neurotoxicity by interfering with the ability of the dopamine neuron to maintain its cytoplasmic pool of transmitter and thereby sustain carrier-mediated dopamine release.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 21
- 5-HT2 receptors exert a state-dependent regulation of dopaminergic function: studies with MDL 100,907 and the amphetamine analogue, 3,4-methylenedioxymethamphetamine European Journal of Pharmacology November 1, 1992
- Studies on the role of dopamine in the degeneration of 5‐HT nerve endings in the brain of Dark Agouti rats following 3,4‐methylenedioxymethamphetamine (MDMA or ‘ecstasy’) administration British Journal of Pharmacology February 1, 1999
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- A study of the mechanism of MDMA (‘Ecstasy’)‐induced neurotoxicity of 5‐HT neurones using chlormethiazole, dizocilpine and other protective compounds British Journal of Pharmacology 1994
- MDMA (3,4-Methylenedioxymethamphetamine) Analogues as Tools to Characterize MDMA-Like Effects: An Approach to Understand Entactogen Pharmacology Current Neuropharmacology August 1, 2013
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