Iwama T, Shikada K, Yamamoto A, Sakashita M, Hibi M, Tanaka S
Shiraoka Research Station of Biological Science, Nissan Chemical Industries, Ltd., Saitama, Japan.
Eur J Pharmacol. 1991 Jul 9;199(3):271-8. doi: 10.1016/0014-2999(91)90490-h.
The effect of NZ-107 (4-bromo-5-(3-ethoxy-4-methoxybenzylamino)-3(2H)-pyridazinone) on late-phase airway responses and airway hyperreactivity was investigated in the guinea pig. Challenge with inhaled ovalbumin in conscious guinea pigs actively sensitized with inhaled ovalbumin caused triphasic bronchial obstruction, which peaked at 5-30 min, 6-8 h and 24 h. In this model, airway hyperreactivity to acetylcholine was observed 48 h after antigen challenge. Orally administered NZ-107, given 2 h before ovalbumin challenge significantly inhibited airway responses at 5-30 min (10 mg/kg), 6-8 h (30 mg/kg), 24 h (10 mg/kg) and airway hyperreactivity (30 mg/kg). When NZ-107 (10 mg/kg) was orally administered to the guinea pigs 3 h after ovalbumin challenge, it also inhibited airway responses at 6-8 h and 24 h and airway hyperreactivity. In anaesthetized guinea pigs, intravenous administration of NZ-107 (0.03-1.0 mg/kg) inhibited platelet-activating factor (PAF)- and propranolol-induced airway hyperreactivity to histamine. These results suggest that NZ-107 may be a useful drug for the treatment of bronchial asthma by reducing late-phase airway responses and airway hyperreactivity.
研究了NZ-107（4-溴-5-（3-乙氧基-4-甲氧基苄基氨基）-3（2H）-哒嗪酮）对豚鼠迟发性气道反应和气道高反应性的影响。对经吸入卵清蛋白主动致敏的清醒豚鼠吸入卵清蛋白进行激发，可引起三相支气管阻塞，分别在5 - 30分钟、6 - 8小时和24小时达到峰值。在该模型中，抗原激发后48小时观察到对乙酰胆碱的气道高反应性。在卵清蛋白激发前2小时口服给予NZ-107，显著抑制了5 - 30分钟（10毫克/千克）、6 - 8小时（30毫克/千克）、24小时（10毫克/千克）的气道反应以及气道高反应性（30毫克/千克）。当在卵清蛋白激发后3小时给豚鼠口服NZ-107（10毫克/千克）时，它也抑制了6 - 8小时和24小时的气道反应以及气道高反应性。在麻醉的豚鼠中，静脉注射NZ-107（0.03 - 1.0毫克/千克）可抑制血小板活化因子（PAF）和普萘洛尔诱导的气道对组胺的高反应性。这些结果表明，NZ-107可能是一种通过减少迟发性气道反应和气道高反应性来治疗支气管哮喘的有用药物。
