Open AccessPharmacological Studies of FUT-175, Nafamostat Mesilate V. Effects on the Pancreatic Enzymes and Experimental Acute Pancreatitis in Rats
Author(s) -
Masahiro Iwaki,
Yoshitaka Ino,
Akemi Motoyoshi,
Masayuki Ozeki,
Takuo Sato,
Masateru Kurumi,
Toshihiro Aoyama
Publication year - 1986
Publication title -
japanese journal of pharmacology/japanese journal of pharmacology
Language(s) - English
Resource type - Journals
eISSN - 1347-3506
pISSN - 0021-5198
DOI - 10.1254/jjp.41.155
Subject(s) - aprotinin , enteropeptidase , acute pancreatitis , trypsin , pancreatitis , in vivo , pharmacology , medicine , in vitro , pancreatic disease , protease , enzyme inhibitor , enzyme , pancreas , chemistry , biochemistry , biology , recombinant dna , microbiology and biotechnology , fusion protein , gene
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.