Pharmacological studies of FUT-175, nafamostat mesilate. V. Effects on the pancreatic enzymes and experimental acute pancreatitis in rats.

  title={Pharmacological studies of FUT-175, nafamostat mesilate. V. Effects on the pancreatic enzymes and experimental acute pancreatitis in rats.},
  author={Masahiro Iwaki and Yoshitaka Ino and A Motoyoshi and Masayuki Ozeki and Takayuki Sato and Masateru Kurumi and Takuo Aoyama},
  journal={Japanese journal of pharmacology},
  volume={41 2},
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… 
The effects of nafamostat mesilate (FUT-175) on caerulein-induced acute pancreatitis in the rat
  • J. Wisner, S. Ozawa, I. Renner
  • Medicine
    International journal of pancreatology : official journal of the International Association of Pancreatology
  • 1989
Data indicate that serine proteases appear to be involved in the pathogenesis of CR induced AP in rats and that FUT-175 administered in low doses (2.5–10.0 mg/kg/h) provides significant protection against this form of pancreatitis.
Comparison of different treatment modalities in experimental pancreatitis in rats.
Lipolytic enzymes may play a role in the pathogenesis of acute pancreatitis. Therefore, the effects of a lipase inhibitor, THL (tetrahydrolipstatin), a protease inhibitor, FUT (nafamostat mesilate),
Effects of the trypsin inhibitor urinastatin on taurocholate-induced pancreatic cellular damage in rats
Investigation of the effects of urinastatin (UTI), a purported trypsin inhibitor, on acute cellular damage in the pancreas suggests that UTI may substantially inhibit the pancreatic damage induced by taurocholate.
Effect of 5‐Fluorouracil on Secretion and Synthesis of Pancreatic Digestive Enzymes: Studies in Isolated Pancreatic Acini and Perfused Pancreas Derived from Normal Rats and from Rats with Acute Necrotizing Pancreatitis
The data may conclude that the data, derived from experimental pancreatitis in rats, do not encourage investigation of the effect of SFU, an anticancer drug with possibly toxic side effects, in human pancreatitis.
The effect of nafamostat mesilate on the prevention of cerulein-induced acute pancreatitis
Background : Many protease inhibitors show a protective effect for acute pancreatitis as seen in animal models. In previous studies, the protease inhibitors were administered before induction of
Effect of a synthetic protease inhibitor (Fut-175) on coagulation abnormalities during experimental acute pancreatitis in dogs
Fut-175 seems to be an effective inhitor of protease-mediated hypercoagulation and fibrinolysis in severe acute pancreatitis.
Continuous Regional Application of Protease Inhibitor in the Treatment of Acute Pancreatitis
The dose as well as the route of protease inhibitors should be carefully considered to achieve its beneficial effect and pancreatic parenchyma in CRI application animals was remarkably preserved.
Effects of Nafamostat Mesilate on the Prevention of Cerulein-Induced Acute Pancreatitis
The development of pancreatitis was prevented by treating mice with nafamostat mesilate before induction, however, this finding was not observed if administered after injection of cerulein.
Protective effect of nafamostat mesilate
SummaryThis in vivo and in vitro study demonstrates the protective effects of a new synthetic protease inhibitornafamostat mesilate, FUT-175—on increased cellular and lysosomal fragility within
Inhibitory effects of ONO-3307 on various proteases and tissue thromboplastin in vitro and on experimental thrombosis in vivo.
The results indicate that ONO-3307 exhibits a wide range of inhibitory effects on various proteases, and it may be useful for the treatment of protease-mediated diseases such as thrombosis and DIC.


[Pharmacological studies of FUT-175, nafamstat mesilate. II. Effects on experimental acute pancreatitis].
FUT-175 infused i.v. at a dose range of 5-50 micrograms/kg/min inhibited the increase in plasmatrypsin activity and reduced the mortality of rabbits in trypsin-induced acute pancreatitis in a dose-dependent manner, suggesting that FUT- 175 is beneficial as a therapeutic agent of acute pancreatritis.
Pharmacological studies of FUT-175, nafamstat mesilate. I. Inhibition of protease activity in in vitro and in vivo experiments.
FUT-175 was highly effective in that, for example, intravenous dosing at 3 mg/kg could completely protect guinea pigs from the lethal Forssman shock and was also found to be effective in trypsin-induced shock in mice, in lethality due to thrombin-thrombosis in mice and in kinin formation in the inflammatory process in rats.
[Therapeutic effects of human urinary trypsin inhibitor on acute experimental pancreatitis].
Results suggest that MTI may suppress pathogenesis and development of pancreatitis in several ways, for example, by directly inhibiting trypsin and by inhibiting tissue-damaging enzymes released from the pancreas by stimulation withtrypsin.
Inhibitory effect of aprotinin and gabexate mesilate on human plasma kallikrein.
  • M. Nakahara
  • Chemistry, Medicine
  • 1983
It is concluded that a predominant effect of aprotinin in human plasma is due to its stability in contrast to instability of gabexate mesilate.
The object of the present investigation is to measure the liberation of proteolytic enzymes in pancreatitis and to relate this to the release of substances affecting vascular smooth muscle and capillary permeability.
Measurement of the rate of plasmin action on synthetic substrates.
  • P. S. Roberts
  • Medicine, Biology
    The Journal of biological chemistry
  • 1958
The Hestrin method is modified so that enzyme rates at optimal substrate concentrations of either TAME or LME can be determined by using the same standard reagents and procedures and the rate measurements are reproducible with an average deviation of 3 per cent of the rate.
On the physiological role of 2 -macroglobulin.
Thrombin bound by α 2 -macroglobulin bound thrombin, contrary to earlier reports, was found to retain clotting activity although at a reduced rate and may play a role in the “hemostatic balance”.
The effects of Ca2+ on porcine enteropeptidase activity
Abstract The activity of porcine enteropeptidase was inhibited by low concentrations of EDTA suggesting a requirement for a divalent metal ion in the catalysis. The Group IIA metal ions, CA2+, Sr2+
New synthetic inhibitors of C1r, C1 esterase, thrombin, plasmin, kallikrein and trypsin.
6'-amidino-2-naphthyl-4-guanidinobenzoate dihydrochloride, 4-(beta- amidinoethenyl)phenyl- 4-guAnidin Obenzoates dimethanesulfonate and 4-amidinos2-benzoylphenyl the most effective inhibitors of trypsin, plasmin, pancreatic kallikrein and thrombin.