[Pharmacological studies of FUT-175, nafamstat mesilate. III. Anti-inflammatory activities of FUT-175].
Anti-inflammatory effects of FUT-175 (nafamstat mesilate), a new synthetic serine protease inhibitor, on various types of experimental inflammation were investigated in vivo and in vitro, in comparison with non-steroidal anti-inflammatory drugs (NSAID). The in vivo studies showed that FUT-175 has the abilities to inhibit almost all types of inflammatory reactions employed in the present study. In particular, being evaluated on the basis of the effect of indomethacin, FUT-175 exhibited relatively higher potencies against some reactions such as zymosan-induced increase of vascular permeability, scald paw edema, zymosan-induced granuloma-pouch, the Arthus reaction and acetic acid-induced writhing in which the complement system or the kallikrein-kinin system are considered to play an important role. The in vitro studies showed that FUT-175 is quite different from NSAID, that is, FUT-175 had no effects on heat-induced erythrocyte-lysis and heat-induced denaturation of bovine serum albumin. FUT-175 also had no effect on chemotaxis of polymorphonuclear leucocytes, but inhibited the production of chemotactic factor by antigen-antibody reaction. These above results suggested that FUT-175 has a different mode of action from NSAID and that serine protease inhibiting activities of this compound might play an important role in its anti-inflammatory effect.
D000818:Animals; D000893:Anti-Inflammatory Agents; D001183:Arthus Reaction / Q000188:drug therapy; D001550:Benzamidines; D002199:Capillary Permeability / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004487:Edema / Q000188:drug therapy; D006146:Guanidines / Q000494:pharmacology* / Q000627:therapeutic use; D006168:Guinea Pigs; D006461:Hemolysis / Q000187:drug effects; D006968:Hypersensitivity, Delayed / Q000188:drug therapy; D008297:Male; D051379:Mice; D011817:Rabbits; D051381:Rats; D014361:Trypsin Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use
D000893:Anti-Inflammatory Agents; D001550:Benzamidines; D006146:Guanidines; D014361:Trypsin Inhibitors; C032855:nafamostat