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Zacopride in Schizophrenia: A Single-blind Serotonin Type 3 Antagonist Trial

John W. Newcomer, MD; William O. Faustman, PhD; Robert B. Zipursky, MD; John G. Csernansky, MD
Arch Gen Psychiatry. 1992;49(9):751-752. doi:10.1001/archpsyc.1992.01820090079013.
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To the Editor.—  Zacopride hydrochloride, a substituted benzamide, is a potent and selective antagonist at serotonin type 3 (5-HT3) receptors' that are found in brain areas receiving mesolimbic dopamine input.2 Much interest has been generated by reports that direct infusion of zacopride and other 5-HT3 antagonists into these mesolimbic areas in the rat inhibits dopaminergically mediated locomotor behavior without the overall depression of the central nervous system or rebound hyperlocomotion produced by conventional neuroleptic srugs.3 Zacopride has also been reported by some4 but not all5 investigators to have potent anxiolytic properties in animal models. Generally inactive at D2 dopamine receptors6 and other neurotransmitter receptors,7,8 this compound does not elevate plasma prolactin levels or cause catalepsy. Accordingly, zacopride has been hypothesized to have efficacy in the treatment of schizophrenia, without the side effects associated with conventional neuroleptic drugs. We sought to provide

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