Reference

Pharmacological studies of FUT-175, nafamstat mesylate

Pharmacological studies of FUT-175, nafamstat mesylate. I. Inhibition of protease activity in in vitro and in vivo experiments. Aoyama, Takuo; Ino, Yoshitaka; Ozeki, Masayuki; Oda, Minoru; Sato, Takuo; Koshiyama, Yoshiko; Suzuki, Shoshi; Fujita, Mitsunobu (Res. Lab., Torii and Co., Ltd., Ichikawa 272, Japan). Jpn. J. Pharmacol., 35(3), 203-27 (English) 1984. CODEN: JJPAAZ. ISSN: 0021-5198. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) FUT-175 (I) [82956-11-4], a novel synthetic protease [9001-92-7]-inhibiting agent, was studied to det. its in vitro effects against various proteases and other enzymes, as well as to det. its in vivo protease inhibitory effects. FUT-175 inhibited, in an intense, specific and reversible way, the enzyme activities of trypsin [9002-07-7], C1r [80295-69-8], C1s [80295-70-1], thrombin [9002-04-4], kallikrein [9001-01-8], and plasmin [9001-90-5] with IC50 values of the order of 10-6-10-8 M. FUT-175 also inhibited complement-mediated hemolysis, including both classical and alternative pathways, the sites of inhibition being on C1r and C1s. In animal model reactions in which the complement system is known to be involved as a pathogenic factor, e.g., Forssman shock, Forssman cutaneous vasculitis, zymosan-induced paw edema, endotoxin shock, and local Shwartzman reaction, FUT-175 was highly effective; for example, i.v. dosing at 3 mg/kg could completely protect guinea pigs from otherwise lethal Forssman shock. FUT-175 was also found to be effective in trypsin-induced shock in mice, against lethality due to thrombin-thrombosis in mice and in kinin formation in the inflammatory process in rats.

Pharmacological studies of FUT-175, nafamstat mesylate

Pharmacological studies of FUT-175, nafamstat mesylate. III. Anti-inflammatory activity of FUT-175. Iwaki, Masahiro; Oda, Minoru; Ozeki, Masayuki; Ino, Yoshitaka; Suzuki, Kunihiko; Koshiyama, Yoshiko; Motoyoshi, Akemi; Ogihara, Madoka; Suzuki, Shoshi; et al. (Res. Lab., Torii and Co., Ltd., Ichikawa 272, Japan). Nippon Yakurigaku Zasshi, 84(4), 373-84 (Japanese) 1984. CODEN: NYKZAU. ISSN: 0015-5691. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) The antiinflammatory effects of FUT-175 (I) [82956-11-4] on various types of exptl. inflammation were examd. in vivo and in vitro, in comparison with the effects of nonsteroidal antiinflammatory drugs (NSAID). FUT-175 inhibited in vivo almost all types of inflammatory reactions employed in the present study. When the effects were compd. with those of indomethacin, FUT-175 showed higher potencies than those of indomethacin against some reactions, such as zymosan-induced increase in vascular permeability, scald paw edema, zymosan-induced granuloma-pouch, the Arthus reaction, and AcOH-induced writhing in which the complement system or the kallikrein-kinin system are considered to play an important role. The effect of FUT-175 in vitro is quite different from NSAID. FUT-175 had no effects on heat-induced erythrocyte-lysis and heat-induced denaturation of BSA. FUT-175 had no effect on chemotaxis of polymorphonuclear leukocytes, but inhibited the prodn. of chemotactic factor by antigen-antibody reaction. Serine protease inhibiting activity of FUT-175 may play an important role for the antiinflammatory effect.