Devazepide antagonizes the inhibitory effect of cholecystokinin on intake in sham-feeding rats.
3S(-)-N-(2,3-Dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepine-3-yl) -1H-indole-2-carboxamide (devazepide), a potent and selective cholecystokininA (CCKA) antagonist, has been shown to reverse the inhibitory effect of exogenously administered CCK-8 on food intake. In all tests, however, the inhibition of food intake could have been due not only to the CCK-8 administered but also to synergistic interactions between administered CCK-8 and endogenous satiety signals, such as glucagon or CCK released from the small intestine, elicited by the postingestive effects of the test diet. To eliminate these possible interactions, we investigated the effect of devazepide on the inhibitory effect of CCK-8 on the intake of a milk diet during 30 min of sham feeding, a procedure that minimizes or eliminates the postingestive satiating effect of food. Under these conditions, devazepide was a potent antagonist of the inhibitory effect of CCK-8 (16 mumol/kg, IP): The approximate ED50 was 625 ng/kg (1.3 nmol/kg) and the threshold dose was between 62.5 and 625 ng/kg.
Melville
L D
LD
Department of Psychiatry, Cornell University Medical College, New York, NY 10021.
Smith
G P
GP
Gibbs
J
J
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D002766:Cholecystokinin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D020109:Devazepide; D004435:Eating / Q000187:drug effects*; D005508:Food Deprivation; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012528:Satiety Response / Q000187:drug effects
D001570:Benzodiazepinones; D002766:Cholecystokinin; D020109:Devazepide