The antagonistic activity of oral
YM158 (3-[(4-tert-butylthiazol-2-yl)methoxy]-5'-[3-(4-chlorobenzenesu lfonyl)propyl]-2'-(1H-tetrazol-5-ylmethoxy)
benzanilide monosodium
salt monohydrate), a new dual antagonist for
leukotriene (LT) D4 and
thromboxane (TX) A2 receptors, was investigated. Oral
YM158 caused dose-dependent inhibition of LTD4-induced increases in plasma leakage and LTD4- or U46619-induced increases in airway resistance, with ED50 values of 6.6, 8.6 and 14 mg/kg, respectively. The dose-range of
YM158's inhibitions was almost the same for both
LTD4 and TXA2 receptors, and repeated oral doses did not affect its efficacy. Furthermore, oral
YM158 inhibited
antigen-induced bronchoconstriction. Although the potency of
pranlukast for
LTD4 receptor antagonism (ED50 = 0.34 mg/kg) is greater than that of
YM158 (ED50 = 8.6 mg/kg), the doses of both
pranlukast and
YM158 for significant inhibition of the
antigen-evoked airway response were the same, indicating that the TXA2 receptor antagonism of
YM158 plays an important role in its
anti-asthmatic effects. In conclusion,
YM158 promises to be a novel agent for treating
bronchial asthma.