title: CR-1409: a potent inhibitor of cholecystokinin-stimulated amylase release and cholecystokinin binding in rat pancreatic acini.
abstract: The effects of a new glutaramic acid derivative, 3,4-dichloro-benzamido-N, N-dipentyl-glutaramic acid (CR-1409), on cholecystokinin-stimulated amylase release and 125I-cholecystokinin octapeptide binding were studied in isolated rat pancreatic acini. CR-1409 at concentrations between 0.3 and 30 microM inhibited cholecystokinin-stimulated amylase release in a dose-dependent manner without appreciable effect on the basal amylase secretion. Biphasic dose-response curves to cholecystokinin for amylase release shifted to the right with an increase in the concentration of the drug. IC50 (half-maximal inhibitory concentration) of CR-1409 for cholecystokinin-stimulated amylase release was 0.64 microM, and the potency of this drug on the inhibition of amylase release was 3400 times greater than that of proglumide. The effect of CR-1409 was rapid, reversible, and selective for cholecystokinin. In addition, CR-1409 at concentrations between 0.1 and 30 microM inhibited 125I-cholecystokinin octapeptide binding to rat pancreatic acini. IC50 of CR-1409 for 125I-cholecystokinin octapeptide binding was 0.22 microM, and the potency of this drug on the effect was 5900 times greater than that of proglumide.
mesh_terms: D000681:Amylases / Q000378:metabolism*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005973:Glutamine / Q000031:analogs & derivatives*; D008297:Male; D019832:N-Methylscopolamine; D010179:Pancreas / Q000378:metabolism*; D011377:Proglumide / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011949:Receptors, Cholecystokinin / Q000378:metabolism*; D012602:Scopolamine Derivatives / Q000378:metabolism; D012844:Sincalide / Q000037:antagonists & inhibitors / Q000494:pharmacology*
chemical_list: D011949:Receptors, Cholecystokinin; D012602:Scopolamine Derivatives; D005973:Glutamine; D000681:Amylases; D011377:Proglumide; C048181:lorglumide; D012844:Sincalide; D019832:N-Methylscopolamine