Suda H, Nagai H, Iwama T, Koda A
Department of Pharmacology, Gifu Pharmaceutical University, Japan.
Int Arch Allergy Immunol. 1992;97(3):187-93. doi: 10.1159/000236117.
The effect of 4-bromo-5-(3-ethoxy-4-methoxybenzylamino)-3(2H)-pyridazinone (NZ-107) on bronchoconstriction in guinea pigs was studied (1). The antigen-induced bronchoconstriction was studied in guinea pigs which had been passively sensitized by intravenous injection of antiserum containing anti-benzylpenicilloyl bovine-gamma-globulin IgE antibody. The sensitized guinea pigs were divided into two groups; one group was pretreated with metyrapone (11 beta-hydroxylase inhibitor in glucocorticoid metabolism) and the other with saline. The antigen-induced bronchoconstriction in the metyrapone-treated animals was more severe than that in the saline-treated animals. The asthmatic respiratory changes, in terms of prolongation of the ratio between expiration and inspiration, was also dramatically increased. NZ-107 at doses of 25 and 50 mg/kg significantly inhibited antigen-induced bronchoconstriction in both the saline-and metyrapone-treated animals. NZ-107 showed a tendency to inhibit accelerated severe asthmatic respiration more strongly in metyrapone-treated animals than in those treated with saline. Salbutamol inhibited antigen-induced bronchoconstriction in saline-treated animals, but its efficacy decreased in metyrapone-treated animals. Unlike salbutamol, prednisolone and hydrocortisone showed the reverse effect, inhibiting bronchoconstriction in metyrapone-but not in saline-treated animals. Sodium cromoglycate inhibited antigen-induced bronchoconstriction in both saline- and metyrapone-treated animals (2). When a subthreshold dose of platelet-activating factor was injected into guinea pigs, airway responsiveness against histamine was clearly increased. NZ-107 at a dose of 0.2 mg/kg i.v. inhibited PAF-induced airway hyperreactivity.(ABSTRACT TRUNCATED AT 250 WORDS)
研究了4-溴-5-(3-乙氧基-4-甲氧基苄基氨基)-3(2H)-哒嗪酮（NZ-107）对豚鼠支气管收缩的影响（1）。在通过静脉注射含抗苄青霉素酰牛γ-球蛋白IgE抗体的抗血清而被动致敏的豚鼠中研究了抗原诱导的支气管收缩。将致敏的豚鼠分为两组；一组用美替拉酮（糖皮质激素代谢中的11β-羟化酶抑制剂）预处理，另一组用生理盐水预处理。美替拉酮处理的动物中抗原诱导的支气管收缩比生理盐水处理的动物更严重。就呼气与吸气之比的延长而言，哮喘性呼吸变化也显著增加。25和50mg/kg剂量的NZ-107在生理盐水处理和美替拉酮处理的动物中均显著抑制抗原诱导的支气管收缩。NZ-107在美替拉酮处理的动物中比在生理盐水处理的动物中更倾向于更强烈地抑制加速的严重哮喘性呼吸。沙丁胺醇在生理盐水处理的动物中抑制抗原诱导的支气管收缩，但在美替拉酮处理的动物中其疗效降低。与沙丁胺醇不同，泼尼松龙和氢化可的松显示出相反的效果，在美替拉酮处理而非生理盐水处理的动物中抑制支气管收缩。色甘酸钠在生理盐水处理和美替拉酮处理的动物中均抑制抗原诱导的支气管收缩（2）。当向豚鼠注射亚阈值剂量的血小板活化因子时，对组胺的气道反应性明显增加。静脉注射0.2mg/kg剂量的NZ-107抑制PAF诱导的气道高反应性。（摘要截短于250字）
