A NEW CCK-A ANTAGONIST, KSG-504, ADMINISTERED INTRADUODENALLY, INHIBITS PANCREATIC-SECRETION IN RATS

We studied the effect in anesthetized rats of a new cholecystokinin (C CK) receptor antagonist developed in Japan, KSG-504, administered intr aduodenally, on pancreatic exocrine secretion stimulated by exogenous CCK and intraduodenal casein. Intraduodenal administration of KSG-504 in graded doses of 2.5-50 mg/kg/h produced dose-dependent inhibition o f pancreatic juice volume and amylase output stimulated by intravenous infusion of CCK-8 in a dose of 0.06 mu g/kg/h. The ID50 (half-maximal inhibition dose) of KSG-504 for CCK-8-stimulated amylase secretion wa s 3.4 mg/kg/h. Moreover, intraduodenal KSG-504 (5 and 25 mg/kg/h) dose dependently suppressed pancreatic juice volume, and amylase output in creased with intraduodenal infusion of casein (400 mg/h). It is conclu ded that KSG-504 administered intraduodenally has a significant, poten t inhibitory action on the exocrine pancreas stimulated by exogenous C CK and intraduodenal casein.