Selective 5-hydroxytryptamine2 receptor antagonists
protect against the neurotoxicity of methylenedioxymethamphetamine in rats

by
Schmidt CJ, Abbate GM, Black CK, Taylor VL.
Merrell Dow Research Institute, Cincinnati, Ohio.
J Pharmacol Exp Ther 1990 Nov;255(2):478-83


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.

Zinc
PBN
History
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L-cysteine
L-deprenyl
Ketanserin
MDMA/MDE
L-tryptophan
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