The Effect of Long-Term Administration of Lorglumide (CR 1409) on Rat Pancreatic Growth and Enzyme Composition

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Abstract
The effects of lorglumide (CR 1409), a potent cholecystokinin (CCK) receptor blocker developed recently by the Rotta Research Laboratories, were studied on pancreatic growth and enzyme composition. In secretory studies, the inhibitory effect of 4 mg/kg of lorglumide administered subcutaneously proved to last more than 3 h. The trophic effect of exogenous CCK (600 ng/kg given three times daily for 2 weeks) was significantly decreased by the simultaneous administration of 4 mg/kg of lorglumide. To study the role of endogenous CCK release by feeding while maintaining pancreatic trophism, 4 mg/kg of lorglumide was administered subcutaneously four times daily during the feeding period for 2 weeks. Lorglumide significantly decreased pancreatic weight, pancreatic content of soluble protein, trypsinogen, and chymotrypsinogen, while decreases in DNA, lipase, and amylase failed to reach statistical significance. According to our experiments, high-doses of lorglumide could inhibit not only the trophic effect of exogenous CCK but also the effect of endogenous CCK released by food and lorglumide itself.

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