Abstract
Clozapine is a dibenzodiazepine derivative with proven antipsychotic efficacy in treatme_nt-refractory schizophrenic patients (Kane et a11988). It is considered an atypical neuroleptic due to its low incidence of extrapyramidal side effects (Kane et a11988), its inability to produce catalepsy (Biirki et al 1975) or block apomorphine-induced stercotypy in animals (Ljungberg and Ungerstedt 1978), and its failure to significantly elevate serum prolactin (Prl) levels (Meltzer et al 1979). Serotonin (5-hydroxytryptamine [5-HT]) agonists are known to stimulate Prl release (Martin and Reichlin 1987). This effect is blocked by 5-HT antagonist agents (Martin and Reichlin 1987). PreclinicaI studies suggest that clozapine is a potent 5-HT antagonist (Fink et al 1984; Lee and Tang 1984). We chose a neuroendocrine strategy to study clozapine's effect on the serotonergic system of schizophrenic patients. Fentturamine, a 5-HT agonist, was used as a serotonergic probe. Clozapine's ability to inhibit the Prl response to fenfluramine would suggest 5-HT antagonistic properties in humans.
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