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The tonic inhibition of prolactin (PRL) secretion, which appears to be sustained mainly by hypothalamic dopaminergic activity, can be reliably disinhibited by neuroleptic, antidopaminergic drugs. The heuristic potential of this PRL response as a neuroendocrine model for studying hypothalamicpituitary regulation in man initiated the present intensive investigation.Nineteen normal young men were studied in a series of weekly experiments; at each session a single drug and dose, out of seven neuroleptic drugs in various doses, was given parenterally (mostly im). Plasma PRL concentrations were then monitored for at least 3 h. 1. Repeated administrations of haloperidol (1 mg im) and prochlorperazine (4 mg iv) demonstrated a high reproducibility of the PRL response within a subject. 2. The PRL-response to four doses of haloperidol, ranging from 0.25 mg to 1.5 mg, showed a sigmoid dose-response curve. A dose as small as 1.5 mg of haloperidol induced maximal PRL response. 3. Dose-PRL response curves of haloperidol, prochlorperazine, and thiothixene, representing three chemical classes of neuroleptic drugs, showed a parallel relationship. This suggests a common pharmacological, very likely antidopaminergic, mechanism of the drugs when releasing PRL. 4. In response to haloperidol (1 mg), chlorpromazine (25 mg), and trifluoperazine (4 mg), plasma PRL concentrations remained elevated for at least 7 h, consistent with reported plasma half-lives of these drugs. 5. Dose equivalencies of seven neuroleptic drugs in inducing PRL secretion in man are given.The presented data indicate that the PRL response to neuroleptic drugs is sensitive and reliable and is probably a valid test of dopaminergic blockade in man. Our findings suggest a model for studying drug and hormonal interactions with neuroleptics in man. (J Clin Endocrinol Metab 45: 996, 1977)

Serial plasma clozapine levels and serum prolactin levels were determined in two schizophrenic patients receiving clozapine, a novel antipsychotic drug. Despite marked therapeutic response and substantial clozapine blood levels, prolactin levels obtained 11--12 h after the last oral dose were unaffected or only minimally elevated. This confirms previous evidence of clozapine's unusual characteristics.

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