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.