Prolactin releasing potencies of antipsychotic and related nonantipsychotic compounds in female rats: relation to clinical potencies.

Prolactin responses to various intraperitoneal doses of nine antipsychotic and related nonantipsychotic compounds were measured in the sera of female rats. At doses of 50 mg/kg or less, all drugs stimulated prolactin. Dose-response curves indicated the following order of prolactin stimulating potency: haloperidol greater than reduced haloperidol congruent to lenperone greater than chlorpromazine greater than AHR-1900 greater than thioridazine greater than clozapine greater than U-25927 greater than SCH-12679. This ranking does not agree entirely with the ranking of relative antipsychotic potency of these compounds. The butyrophenone AHR-1900 is inactive clinically, whereas clozapine is a more potent antipsychotic agent than chlorpromazine. The relation between prolactin-stimulating potency and reported clinical potency was improved by comparing drugs within the same chemical classification: AHR-1900 was only one-sixtieth as potent as haloperidol in stimulating prolactin secretion. Reduced haloperidol, a major metabolite of haloperidol, was one-fourth as potent as haloperidol in stimulating prolactin release, suggesting that the potential antipsychotic activity of reduced haloperidol should be investigated.