Inhibition of various immunological reactions in vivo by a new synthetic complement inhibitor.
FUT-175 (6 amidino-2-naphthyl-4-guanidino benzoate-dimethanesulfonate), a new synthetic protease inhibitor, inhibits the enzyme activities of various proteases, such as Clr, C1 esterase, thrombin, kallikrein, plasmin and trypsin. FUT-175 strongly inhibited complement-medicated hemolysis via the classical and alternative pathways. The effects of FUT-175 on various immunological reactions in vivo were studied. The minimal effective dose of FUT-175 in systemic Forssman shock in guinea pigs was 6.25 mg/kg i.p. and 25 mg/kg p.o. In passive Arthus reactions in rats, the effective dose was 25 mg/kg i.p. and 250 mg/kg p.o. FUT-175 also inhibited other immunological reactions, such as passive cutaneous anaphylaxis and delayed hypersensitivity. Furthermore, at a dose of 25 mg/kg i.p. it strongly protected mice from death in endotoxin shock.
D000818:Animals; D001183:Arthus Reaction / Q000276:immunology; D001550:Benzamidines; D003169:Complement Inactivator Proteins; D005577:Forssman Antigen; D006146:Guanidines / Q000494:pharmacology*; D006168:Guinea Pigs; D006461:Hemolysis; D008297:Male; D051379:Mice; D010323:Passive Cutaneous Anaphylaxis; D051381:Rats; D011919:Rats, Inbred Strains; D012769:Shock / Q000276:immunology; D012772:Shock, Septic / Q000276:immunology
D001550:Benzamidines; D003169:Complement Inactivator Proteins; D006146:Guanidines; D005577:Forssman Antigen; C032855:nafamostat