Protective effect of CR 1409 (cholecystokinin antagonist) on experimental pancreatitis in rats and mice

Role of Cholecystokinin in the Development and Progression of Acute Pancreatitis and the Potential of Therapeutic Application of Cholecystokinin Receptor Antagonists

“…Several studies reported beneficial effects of CCK receptor blockade in pancreatitis induced by perfusion of the pancreatic duct with sodium taurocholate in rats [49], by retrograde infusion of sodium taurocholate in rats [50, 51], and by direct injection of sodium taurocholate into the pancreatic parenchyma in rats [45]. It has also been reported that the CCK-receptor antagonist lorglumide ameliorated taurocholate-induced pancreatitis in rats by normalizing the proteinase-antiproteinase balance [59].…”

“…Several studies reported beneficial effects of CCK-receptor blockade in pancreatitis induced by CDE diet in mice [3], by perfusion of the pancreatic duct with sodium taurocholate in rats [49], by mechanical trauma in guinea pigs [49], by retrograde infusion of sodium taurocholate in rats [50, 51], by direct injection of sodium taurocholate into the pancreatic parenchyma in rats [45], by closed duodenal loop in rats [52]and in an isolated rat pancreas preparation [53]. Other studies, however, failed to show significant beneficial effects of CCK-receptor blockade against pancreatitis induced by CDE diet in mice [54, 55]or by retrograde infusion of sodium taurocholate in rats [56].…”

Cholecystokinin and gastrin antagonists

“…The enantiomer derived from D-glutamic acid showed a 50-fold greater affinity for pancreatic acini receptors than the L-enantiomer. 36, 39 Proglumide has been reported to have delta opiate agonist activityr4' while lorglumide has very good selectivity for contractions elicited in smooth muscles by CCK compared with a number of peptide and classical neurotransmitter agent^.^,^^,^* An analog of lorglumide in which oxygen replaces one methylene, 12 (CR 1505, loxiglumide), has properties similar to those of lorglumide and is currently undergoing clinical evaluation (Table 11) .42,43 The detailed pharmacological properties of lorglumide and loxiglumide have been reported.%*" Both have been confirmed to be moderately potent, selective CCK-A receptor antagonists in vitro and in vivo. Both are devoid of agonist activity.…”

Synthesis of Substituted 3‐Anilino‐5‐phenyl‐1,3‐dihydro‐ 2H‐1,4‐benzodiazepine‐2‐ones and their Evaluation as Cholecystokinin‐Ligands

“…Lorglumide is a CCK 1 selective antagonist with a low potency and presents chemically an amide derivative of glutamic acid [11,12]. A research group at Parke-Davis [13] examined the activity of CCK-30-33 fragments in binding experiments on CCK 2 /gastrin receptors.…”