| 体内研究： |
YM158, an orally active dual antagonist for LTD4 and TXA2 receptors, is expected to have a stronger antiasthmatic efficacy in a broader class of asthmatic patients than single antagonistic drugs.The effect of YM158 is examined on these asthmatic responses in mediator-controlled and passively sensitized guinea pigs. Because the inhibitory effects of YM158 on increase in the airway resistance induced by LTD4 or U46619 are shown to be dose-dependent when p.o. administered 1 h before LTD4 or U46619 injection, with ED50 values of 8.6 and 14 mg/kg, respectively, the antagonistic activities of p.o. YM158 for LTD4 and TXA2 receptors are exhibited at the same dose range. Oral YM158 shows significant effects, approximately the same as the combination of Pranlukast and Daltroban on antigen-induced response under various conditions; namely, where LTD4 is predominant, TXA2 is predominant; or where both mediators participated equally. In groups not treated with Indomethacin, administration of Daltroban (10 mg/kg), a combination of Pranlukast (30 mg/kg) and Daltroban (10 mg/kg), or YM158 (30 mg/kg) significantly prolongs the onset time for asthmatic response and significantly suppresses symptoms. |
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