A comparison of the effects of anti-psychotic drugs on pituitary, striatal and limbic system post-synaptic dopamine receptors

Dopamine (DA) antagonists promote the secretion of prolactin (PRL) from the anterior pituitary gland by blocking the effects of DA at receptors in the pituitary itself. Thus, comparison of the properties of these receptors with DA receptors in the striatal, meso-limbic and meso-cortical regions is of interest. Evidence is presented that clozapine, RMI-81, 582 (a morphanthridine derivative), trebenzomine (CI-686, a chromanamine derivative) and sultopride (a benzamide) have much weaker effects on human and rat PRL secretion than would be predicted by their anti-psychotic potency. The reverse is true of two other benzamides, sulpiride and metoclopramide. Classical neuroleptics of the phenothiazine, butyrophenone and thioxanthene types appear to affect rat and human PRL secretion in a manner which is mainly but not entirely consistent with their known effects on striatal and meso-limbic/meso-cortical postsynaptic DA receptors. Preliminary studies indicate presynaptic receptors which affect prolactin secretion are not present in rats. Supersensitivity may develop in the tubero-infundibular (TI) system after chronic neuroleptic treatment but altered sensitivity of these receptors was not found in schizophrenics given apomorphine.