Effects of a series of substituted benzamides on rat prolactin secretion and 3H-spiperone binding to bovine anterior pituitary membranes.
The potency of seven substituted benzamide drugs (AHR-5531B, AHR-5645B, AHR-6092, AHR-8764, bromopride, sultopride and tiapride) to stimulate rat prolactin (PRL) secretion in vivo was found to be three orders of magnitude greater than that of non-benzamide neuroleptic drugs relative to their respective abilities to inhibit 3H-spiperone binding to bovine anterior pituitary membranes. Nevertheless, the IC50 values for the inhibition of 3H-spiperone binding by the seven substituted benzamide drugs was significantly correlated with their high potency to stimulate rat PRL secretion in vivo. Further, the slope of the regression line for these substituted benzamides paralleled that of a series of butyrophenone, phenothiazine, morphanthridine and dibenzodiazepine neuroleptic drugs. Two benzamide (sulpiride and metoclopramide) and three non-benzamide neuroleptic drugs gave intermediate results. This data suggests that blockade of different subgroups of dopamine receptors in the anterior pituitary gland labeled by 3H-spiperone may be responsible for the in vivo stimulation of PRL secretion by the benzamide and non-benzamide neuroleptic drugs.
D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D001667:Binding, Competitive; D002090:Butyrophenones / Q000378:metabolism*; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D007700:Kinetics; D008297:Male; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D013134:Spiperone / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013976:Tiapamil Hydrochloride / Q000031:analogs & derivatives / Q000494:pharmacology*
D001549:Benzamides; D002090:Butyrophenones; D011954:Receptors, Dopamine; C031611:spiroperidol receptor; D013134:Spiperone; D011388:Prolactin; D013976:Tiapamil Hydrochloride