Pharmacological Studies of FUT-175, Nafamostat Mesilate V. Effects on the Pancreatic Enzymes and Experimental Acute Pancreatitis in Rats
Open Access
- 1 January 1986
- journal article
- Published by Elsevier BV in The Japanese Journal of Pharmacology
- Vol. 41 (2), 155-162
- https://doi.org/10.1254/jjp.41.155
Abstract
Effects of FUT-175 on the pancreatic enzymes in vitro and in vivo in the enterokinase-induced experimental acute pancreatitis were investigated, and they were compared with those of gabexate and aprotinin. In in vitro experiments, FUT-175 inhibited the pancreatic protease activities 10 to 100 times more potently than gabexate. Furthermore, FUT-175 inhibited the enterokinase activity. Unlike aprotinin, FUT-175 inhibited alpha 2-macroglobulin bound trypsin activity as well as free trypsin. In in vivo experiments, at doses of 0.5-50 micrograms/kg/min, FUT-175 suppressed the elevated protease activities in the experimental acute pancreatitis more potently than gabexate. Differently from the action of aprotinin, FUT-175 suppressed trypsin activities both in the pancreas and in the plasma to the same extent. Furthermore, FUT-175 reduced the mortality of rats in the experimental acute pancreatitis in a dose-dependent manner. These data strongly support that FUT-175 is clinically useful in the therapy of acute pancreatitis.Keywords
This publication has 6 references indexed in Scilit:
- New synthetic inhibitors of C1r̄, C1 esterase, thrombin, plasmin, kallikrein and trypsinBiochimica et Biophysica Acta (BBA) - Enzymology, 1981
- The effects of Ca2+ on porcine enteropeptidase activityBiochimica et Biophysica Acta (BBA) - Enzymology, 1973
- The interaction of α2-macroglobulin with proteinases. Characteristics and specificity of the reaction, and a hypothesis concerning its molecular mechanismBiochemical Journal, 1973
- Studies on α2-Macroglobulin in Bovine Plasma*The Journal of Biochemistry, 1970
- Trypsin Release, Kinin Production, and ShockArchives of Surgery, 1964
- The Role of Pancreatic Enzymes in the Pathogenesis of Acute PancreatitisGastroenterology, 1962