THE EFFECT OF A NOVEL THROMBOXANE-A(2) (TXA(2)) RECEPTOR ANTAGONIST (S-1452) ON THE ANTIGEN-INDUCED BRONCHOCONSTRICTION AND AIRWAY HYPERRESPONSIVENESS IN GUINEA-PIGS

The effect of a novel thromboxane A2 (TXA2) receptor antagonist (S-1452) on antigen-induced bronchoconstriction and airway hyperresponsiveness in guinea pigs was studied. Ketotifen was used as a reference drug. S-1452 at doses of 1 and 3 mg/kg (per oral administration, 1 h before the injection of U-46619) clearly inhibited U-46619-induced pulmonary pressure increase. Ketotifen at a dose of 10 mg/kg did not affect U-46619-induced bronchoconstriction. S-1452 at doses of 3 and 10 mg/kg and ketotifen at a dose of 10 mg/kg inhibited the antigen-induced bronchoconstriction in guinea pigs which had been passively sensitized with guinea pig IgE antibody. S-1452 at a dose of 10 mg/kg inhibited repeated antigen provocation-induced airway hyperresponsiveness in guinea pigs. The accumulation of inflammatory cells by antigen provocation in bronchial alveolar lavage fluid (BALF) was inhibited by ketotifen but not by S-1452. These results indicate the efficacy of S-1452 on antigen-induced bronchoconstriction and antigen-induced airway hyperresponsiveness in guinea pigs.