Lack of effect of cholecystokinin receptor antagonist (CR1505) on recovery of experimental pancreatitis after pancreatic duct occlusion in rats.

The effect of long term administration of a synthetic cholecystokinin (CCK) receptor antagonist CR1505 (loxiglumide) on pancreatitis was examined in rats after pancreatic duct ligation (PL) with an internal bile fistula. All rats were given both 6 mg/day of CR1505 continuously infused intraduodenally with an osmotic pump and 32 mg/day introduced into the stomach with an orogastric tube. Rats were killed 7, 14, and 28 days after PL, and changes of body weight, pancreatic wet weight, daily food intake, pancreatic protein content, and histology, plasma amylase concentration, and both plasma and duodenal CCK concentrations were examined. Administration of CR1505 for 7 days from immediately after PL, resulted in decrease of body weight, increase of daily food intake, and significant increases of intestinal CCK concentration and the level of CCK mRNA. However, its administration from day 7 to day 14 or 28 did not improve any of the parameters examined except inflammatory infiltration of the pancreas on the 14th postoperative day. These results suggest that CR1505 may have a beneficial effect on recovery from pancreatitis when administered during the early stage, but not when administered during a later stage.