Basic biology of clozapine: electrophysiological and neuroendocrinological studies

The effects of clozapine and other purported atypical antipsychotics were compared with those of typical antipsychotics within the neuroendocrine axis of the rat. Atypical antipsychotics (e.g., clozapine, thioridazine, melperone, setoperone and RMI 81582) differed from typical antipsychotics (e.g., haloperidol, chlorpromazine, cis-flupentixol and fluphenazine) in that they produced only a brief elevation in serum concentrations of prolactin but marked increases in serum or plasma concentrations of corticosterone and ACTH. Moreover, atypical antipsychotics, but not typical antipsychotics, acutely increased the activity of tuberoinfundibular dopamine neurons, as judged from the accumulation of DOPA in the median eminence after inhibition of decarboxylase activity. The effects of atypical antipsychotics on tuberoinfundibular dopamine neurons and corticosterone secretion were mimicked by neurotensin. It would appear that atypical antipsychotics elicit unique neuroendocrine responses that differentiate these agents from typical antipsychotic drugs.