Potency of L-364,718 as an antagonist of the behavioral effects of peripherally administered cholecystokinin.
A new antagonist of the peripheral cholecystokinin receptor, L-364,718, was found to block the reductions in food intake and exploratory activity induced by intraperitoneal administration of cholecystokinin octapeptide sulfate. L-364,718 significantly reversed the cholecystokinin-induced reduction in feeding at doses of 10 micrograms/kg - 10 mg/kg i.p. L-364,718 significantly reversed the cholecystokinin-induced reduction in exploratory activity at doses of 500 ng/kg - 10 mg/kg i.p. The time course of antagonist activity of L-364,718 was immediate to 90 minutes after intraperitoneal administration. L-364,718 had no significant effect on food intake or exploratory activity when administered alone, over the dose range of 100 ng/kg-10 mg/kg i.p. This compound appears to be at least one hundred times more potent than proglumide or benzotript as an antagonist of the behavioral effects of peripherally administered cholecystokinin.
Khosla
S
S
Unit on Behavioral Neuropharmacology, National Institute of Mental Health, Bethesda, MD 20892.
Crawley
J N
JN
D000818:Animals; D001066:Appetite / Q000187:drug effects*; D001570:Benzodiazepinones / Q000494:pharmacology*; D020109:Devazepide; D005106:Exploratory Behavior / Q000187:drug effects; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects*; D012844:Sincalide / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D013997:Time Factors
D001570:Benzodiazepinones; D020109:Devazepide; D012844:Sincalide