COMPARISON OF THE EFFECTS OF SUBSTITUTED BENZAMIDES AND STANDARD NEUROLEPTICS ON THE BINDING OF H-3-SPIROPERIDOL IN THE RAT PITUITARY AND STRIATUM WITH INVIVO EFFECTS ON RAT PROLACTIN SECRETION

The abilities of sulpiride, metoclopramide, clozapine, loxapine, chlorpromazine, thioridazine, fluphenazine, haloperidol, (+)-butaclamol and RMI 81,582 to displace 3H-spiroperidol from rat pituitary and striatal membranes in vitro were compared to their abilities to stimulate rat prolactin secretion in vivo. There was a significant correlation between the abilities of clozapine, chlorpromazine, thioridazine, fluphenazine, RMI 81,582, haloperidol and (+)-butaclamol to bind to pituitary and striatal spiroperidol binding sites and to stimulate rat prolactin secretion. Loxapine was somewhat more potent and sulpiride and metoclopramide were markedly more potent in their abilities to stimulate prolactin secretion than would be predicted on the basis of their abilities to bind to pituitary dopamine receptors as measured by antagonism of 3H-spiroperidol binding. The abilities of metoclopramide and sulpiride to increase prolactin secretion and to produce anti-psychotic and extrapyramidal effects may be mediated by action at dopamine receptors which differ from those at which classical neuroleptics act, and they may also be mediated by non-dopaminergic mechanisms. Potency as inhibitors of 3H-neuroleptic binding in the rat pituitary or striatum appears to have heretofore unappreciated limitations to predict physiological functions such as prolactin stimulation and anti-psychotic activity. © 1979.