[Pharmacological studies of FUT-175, nafamstat mesilate. II. Effects on experimental acute pancreatitis].
Effects of FUT-175, a novel synthetic protease-inhibiting agent, on various models of experimental acute pancreatitis were examined. FUT-175 infused i.v. at a dose range of 5-50 micrograms/kg/min inhibited the increase in plasma trypsin activity and reduced the mortality of rabbits in trypsin-induced acute pancreatitis in a dose-dependent manner. Increase in serum amylase activity and pancreatic tissue lesion were attenuated in rabbits. In addition, FUT-175 infused i.v. at a dose range of 1-50 micrograms/kg/min reduced the mortality of rats in experimental acute pancreatitis produced by trypsin and endotoxin. FUT-175 infused i.v. at a dose range of 1-100 micrograms/kg/min protected the dogs from the increase in plasma trypsin activity and hypotension and shock induced by trypsin, well-known characteristics of acute pancreatitis. These results suggest that FUT-175 is beneficial as a therapeutic agent of acute pancreatitis.
D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D001550:Benzamidines; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D005260:Female; D006146:Guanidines / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D010179:Pancreas / Q000473:pathology; D010195:Pancreatitis / Q000188:drug therapy* / Q000473:pathology; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D014361:Trypsin Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*
D001550:Benzamidines; D001786:Blood Glucose; D006146:Guanidines; D014361:Trypsin Inhibitors; D000681:Amylases; C032855:nafamostat