Protective effect of CR 1409 (cholecystokinin antagonist) on experimental pancreatitis in rats and mice.
CR 1409, a glutaramic acid derivative with competitive cholecystokinin-antagonistic activity, was administered IP and evaluated in comparison with proglumide (the model CCK-receptor antagonist), gabexate (protease inhibitor) and PGE2 (cytoprotective) on two different models of experimental pancreatitis. Acute pancreatitis was induced in mice by six IP injections of 50 micrograms/kg caerulein at hourly intervals. The drugs were administered 30 minutes before each caerulein administration. Blood samples and pancreata were collected 3 hours after the last caerulein injection. In the second experiment, pancreatitis was induced in rats by injecting 0.3 ml 6% sodium taurocholate interstitially into the pancreas. The drugs were administered twice, 30 minutes before and 3 hours after taurocholate. The animals were killed 6 hours after laparotomy and blood samples and pancreata were collected. CR 1409 exhibited on both pancreatitis models a protective effect in a dose range of 0.3-10 mg/kg. Proglumide exhibited a protective activity at higher doses (200-400 mg/kg). Gabexate and PGE2 were effective only in pancreatitis induced by taurocholate in a dose range of 30-60 mg/kg and 60-130 micrograms/kg respectively. These results, showing a high protective effect of CR 1409 on different models of acute pancreatitis, suggest an important role of CCK in the pathogenesis of pancreatitis.
D000208:Acute Disease; D000818:Animals; D002108:Ceruletide; D002766:Cholecystokinin / Q000037:antagonists & inhibitors; D015232:Dinoprostone; D004195:Disease Models, Animal; D005260:Female; D016670:Gabexate; D005973:Glutamine / Q000031:analogs & derivatives*; D006146:Guanidines / Q000627:therapeutic use; D008297:Male; D051379:Mice; D010195:Pancreatitis / Q000139:chemically induced / Q000517:prevention & control*; D011377:Proglumide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011458:Prostaglandins E / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains; D013656:Taurocholic Acid
D006146:Guanidines; D011458:Prostaglandins E; D005973:Glutamine; D016670:Gabexate; D013656:Taurocholic Acid; D002108:Ceruletide; D002766:Cholecystokinin; D011377:Proglumide; D015232:Dinoprostone; C048181:lorglumide