Persistent effects of high concentrations of chlorpromazine on 3H-propylbenzilylcholine mustard binding to muscarinic receptors in guinea-pig intestinal muscle strips.

Low concentrations of chlorpromazine inhibited the binding of 3H-propylbenzilylcholine mustard (3H-PrBCM) to muscarinic receptors in strips of longitudinal muscle from guinea-pig small intestine in an apparently competitive manner. Higher concentrations of chlorpromazine, corresponding to the prelytic-lytic range on hypotonic erythrocyte haemolysis, produced an inhibition of the binding of 3H-PrBCM which persisted after washing for 1 hr. Neither 10(-6) M atropine nor 10(-3) M carbachol afforded any protection against this effect. There was no significant inhibition of 3H-PrBCM binding after washing for 1 hr when atropine and carbachol were added alone. The curve for the inhibition of 3H-PrBCM binding by methylatropinium in strips pretreated with chlorpromazine showed a small shift to higher concentrations compared with untreated strips, without any significant effect on the Hill coefficient. In contrast, the Hill coefficient for carbachol binding was significantly increased in the chlorpromazine-treated strips.