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.
Tagami
H
H
Teikoku Chemical Industries Co., Ltd., Itami, Hyogo, Japan.
Abe
S
S
Yoshida
Y
Y
Tanaka
I
I
Kamei
C
C
D000681:Amylases / Q000097:blood; D000818:Animals; D002108:Ceruletide / Q000633:toxicity; D004195:Disease Models, Animal; D004952:Esters; D016670:Gabexate / Q000031:analogs & derivatives*; D006146:Guanidines / Q000627:therapeutic use*; D008297:Male; D010195:Pancreatitis / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology; D011422:Propionates / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013656:Taurocholic Acid / Q000633:toxicity; D014357:Trypsin / Q000633:toxicity; D014361:Trypsin Inhibitors / Q000627:therapeutic use*
C112144:2(S)-(4-(4-guanidinobenzoyloxy)phenyl)propionate methanesulfonate; D004952:Esters; D006146:Guanidines; D011422:Propionates; D014361:Trypsin Inhibitors; C034532:camostat; D016670:Gabexate; D013656:Taurocholic Acid; D002108:Ceruletide; D000681:Amylases; D014357:Trypsin