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目的 观测新型的ATP敏感钾通道开放剂EMD56431(EMD) 的平喘作用,并与钙通道阻滞剂粉防己碱(tetrandrine,Tet)比较。方法 豚鼠离体气管法和整体药物引喘法。结果 EMD 能抑制KCl 所致豚鼠气管螺旋条的收缩反应,其抑制作用随[K+]o 浓度的增高而减弱;EMD 能浓度依赖性地使氨甲酰胆碱和组胺的量效曲线右移,最大效应降低,均表现为非竞争性拮抗,pD′2 值分别为4-45 和4-40 ;组胺喷雾引起的豚鼠哮喘模型中,EMD 灌胃能剂量依赖性地使豚鼠的引喘潜伏期延长,抽搐动物数亦随剂量增加而减少(n = 8 ,P< 0-05)。结论 EMD 的支气管扩张作用在于开放钾通道,其作用强于Tet,两者具有协同作用。EMD 单用或与Tet 小剂量合用显示出较好的效果
Objective To observe the antiasthmatic effect of EMD56431 (EMD), a novel ATP-sensitive potassium channel opener, and to compare with calcium channel blocker tetran-drine (Tet). Methods Guinea pig tracheal tube method and the overall drug asthma method. Results EMD inhibited the contractile response of tracheal spheroids induced by KCl in guinea pigs, and its inhibition was weakened with the increase of [K +] o concentration. EMD shifted the dose-response curve of carbachol and histamine to the right , The maximum effect decreased, showed non-competitive antagonism, pD’2 values ?? were 4-45 and 4-40; Histamine spray-induced guinea pig asthma model, EMD gavage dose-dependent guinea pig asthma Latency was prolonged and the number of convulsions animals also decreased with increasing dose (n = 8, P <0-05). Conclusions The bronchodilator effect of EMD lies in the open potassium channel, which is more effective than Tet, and the synergistic effect of both is found. EMD alone or in combination with Tet low dose showed good results