Küng M, Bangs S E, Gordon E E, Barker K B, Diamond L
Ann Allergy. 1987 Sep;59(3):201-6.
We evaluated the efficacy of an oral dosage form of the investigational smooth muscle relaxant, zindotrine, a novel pyridazine derivative, in counteracting histamine-induced bronchospasm in a group of 12 non-medicated asymptomatic asthmatics. Histamine inhalation challenges were performed before (control) and 45, 150, and 300 minutes after zindotrine (200 and 300 mg), or the corresponding dose of placebo was administered orally in a randomized, double-blind crossover fashion. When compared to the control state, the 300-mg zindotrine dose markedly lowered histamine airway responsiveness as indicated by a significant (P less than .01) increase in the inhaled histamine dose necessary to provoke a 20% decrease in the forced expired volume in one second (PD20FEV1) 45 minutes after drug administration. The PD20FEV1 then decreased linearly over time but remained higher than the control PD20FEV1 value (P less than .05) during the entire observation period. The 200-mg zindotrine dose failed to affect the PD20FEV1. Our data indicate that orally administered zindotrine lowers airways responsiveness to inhaled histamine in asymptomatic asthmatics in a dose-dependent and time-dependent fashion.
我们评估了新型哒嗪衍生物、研究性平滑肌松弛剂津多曲林口服剂型对12名未用药的无症状哮喘患者组胺诱导的支气管痉挛的对抗效果。采用随机、双盲交叉方式，在吸入组胺激发试验前（对照）以及口服津多曲林（200毫克和300毫克）或相应剂量安慰剂后的45、150和300分钟进行试验。与对照状态相比，给药后45分钟，300毫克剂量的津多曲林显著降低了组胺气道反应性，表现为引起一秒用力呼气量下降20%所需的吸入组胺剂量显著增加（P<0.01）。随后，PD20FEV1随时间呈线性下降，但在整个观察期内仍高于对照PD20FEV1值（P<0.05）。200毫克剂量的津多曲林未能影响PD20FEV1。我们的数据表明，口服津多曲林可使无症状哮喘患者气道对吸入组胺的反应性呈剂量和时间依赖性降低。
