The effect of a novel leukotriene C4/D4 antagonist, BAY-x-7195, on experimental allergic reactions.

The effects of a novel leukotriene (LT) C4/D4 antagonist, BAY-x-7195 on experimental allergic reactions in airway and skin were compared to that of ONO-1078. BAY-x-7195 showed an antagonistic action to LTD4-induced bronchoconstriction in vitro and in vivo. In in vitro experiments, BAY-x-7195 inhibited LTD4-induced contraction of isolated guinea pig tracheal muscle (pA2 = 8.03). BAY-x-7195 at doses of 3-30 mg/kg clearly inhibited LTD4-induced increases in respiratory resistance (Rrs) in guinea pigs. In contrast, BAY-x-7195 inhibited significantly U-46619-induced increases in Rrs at a dose of 30 mg/kg in guinea pigs. BAY-x-7195 at doses of 3-30 mg/kg inhibited the aerosolized antigen-induced biphasic increase in Rrs in guinea pigs. Moreover BAY-x-7195 inhibited repeated aeroantigen-induced airway hyperreactivity in guinea pigs. In mice, aeroantigen-induced airway inflammation were clearly inhibited by BAY-x-7195. These results show the efficacy of BAY-x-7195 against the antigen-induced increase in airway resistance and antigen-induced airway hyperreactivity in guinea pigs and mice, probably due to anti-LTD4 antagonistic action and the inhibition of antigen-induced airway inflammation.