Human prolactin responses to neuroleptic drugs correlate with antischizophrenic potency

Abstract

THE secretion of prolactin, a pituitary hormone, is regulated by inhibitory and stimulatory influences from the hypothalamus. The primary influence is tonic inhibitory¹. Dopamine, a neurotransmitter, has a major direct and/or indirect role in mediating this inhibition upon the prolactin cells in the pituitary gland. This is documented by studies in vitro¹, in vivo² and in man³. All known neuroleptic, antischizophrenic drugs share one characteristic—they block dopaminergic transmission^4–7. This action is hypothesised to be associated with their antischizophrenic effects (dopamine hypothesis)^3,9. Dopaminergic blockade is, very likely, also the primary mechanism of neuroleptics when inducing prolactin release via disinhibition^1,10. There is no evidence that neuroleptics release prolactin via stimulatory influences. We believe the prolactin response to neuroleptic drugs to be a valid and reliable model of dopaminergic blockade in man (Langer et al., unpublished). Intesting the dopamine hypothesis of antischizophrenic drug action in man we postulated that comparing drug effects after acute intramuscular administration, a high correlation between prolactin releasing and antischizophrenic potencies of neuroleptics would be found.