Anti-allergic effects of (E)-3-[p-(1H-imidazol-1-ylmethyl)phenyl]-2-propenoic acid (OKY-046), a specific thromboxane (TX) A2 synthetase inhibitor: effect of OKY-046 on II-IV type allergic reactions

We studied the effects of OKY-046 on types II, III and IV allergic reactions, as classified by Coombs and Gell. In Type II, OKY-046 at 30-100 mg/kg intraduodenally (i.d.) and at 1-30 mg/kg intravenously (i.v.) inhibited the bronchoconstriction in a dose-dependent manner after Forssman antigen injection. Aspirin (3 mg/kg, i.v.) also suppressed it. OKY-046 (30-100 mg/kg, i.d.) suppressed the increase of TXB2 level in the plasma in a dose-dependent manner. However, there was no effect of OKY-046 and aspirin on the decrease in complement activity (CH50), platelets and leukocytes. Additionally, OKY-046 (300 mg/kg, p.o.) prolonged the survival time following Forssman antigen injection. However, the immune hemolysis reaction was not prevented by OKY-046 (10(-6)-10(-3) M). FUT-175 protected against the Forssman shock at 1 mg/kg, i.v. and the in vitro immune hemolysis reaction at 10(-5) M. In Type III, OKY-046 (300 mg/kg, p.o.) significantly suppressed the direct passive Arthus reaction and immune complex nephritis in rats. There was no effect of OKY-046 on the delayed-type hypersensitive response to picryl chloride in mice. We think that OKY-046 should be a beneficial drug for the treatment of types II and III allergic reactions.