Effect of methylcarbonylmethyl 2(S)-[4-(4-guanidino-benzoyloxy)phenyl] propionate methanesulfonate (TT-S24) on experimental pancreatitis in rats.

The effect of methylcarbonylmethyl 2(S)-14-(4-guanidino-benzoyloxy) phenyl] propionate methanesulfonate (TT-S24) on experimental pancreatitis in rats was examined in comparison with that of camostat. TT-S24 showed a preventive effect on increases in plasma amylase activity and pancreatic weight induced by cerulein injection. TT-S24 also reduced an increase in plasma amylase activity induced by taurocholate. TT-S24 effectively prevented the mortality induced by an injection of a mixture of trypsin and taurocholate. TT-S24 showed no effect on an increase in amylase activity 6 h after duodenum ligation (closed duodenal loop pancreatitis), indicating that the drug had no effect on the initiation and propagation step of closed duodenal loop pancreatitis. On the other hand, TT-S24 reduced an increase in amylase activity 6 h after release of the duodenum ligation. TT-S24 showed anti-trypsin, anti-kallikrein, anti-thrombin and anti-plasmin activities. The effect of TT-S24 on some experimental pancreatitis models was nearly equal to or somewhat more potent in most instances to that of camostat. Therefore, TT-S24 should be useful in the clinical treatment of pancreatitis.