Nagai H, Suda H, Iwama T, Daikoku M, Yanagihara Y, Koda A
Department of Pharmacology, Gifu Pharmaceutical University, Japan.
Int Arch Allergy Immunol. 1992;98(1):57-63. doi: 10.1159/000236164.
The effects of a newly synthesized pyridazinone derivative, NZ-107, 4-bromo-5-(3-ethoxy-4-methoxybenzylamino)-3(2H)-pyridazinone, and two well-known antiasthmatic drugs, amlexanox (orally active disodium cromoglycate-like drug) and disodium cromoglycate (DSCG) on antigen-, histamine- and leukotriene C4 (LTC4)-induced constriction of isolated human tracheal muscle, and histamine release from human lung tissues and leukocytes were investigated in vitro. In some experiments, salbutamol was used as a reference drug. NZ-107 inhibited antigen-, histamine- and LTC4-induced contraction of tracheal muscle. Amlexanox and DSCG did not affect the contractile response of tracheal muscle caused by each stimulant. Salbutamol inhibited antigen-induced contraction of tracheal muscle. NZ-107, amlexanox, DSCG and salbutamol clearly inhibited the antigen-induced release of histamine and LTC4 from human lung tissue. The antigen-induced histamine release from atopic human leukocytes was inhibited by NZ-107 and amlexanox, but not by DSCG. Pretreatment with IL-3 did not alter antigen-induced contraction of tracheal muscle and histamine release from lung tissue, but antigen- or calcium ionophore A 23187-induced histamine release from leukocytes was clearly enhanced. Amlexanox inhibited the IL-3-induced enhancement of histamine release from leukocytes in the case of both stimuli, but NZ-107 and DSCG had no effect. These data suggest that NZ-107 has potent anti-allergic actions based on the inhibition of antigen-induced contraction of human tracheal muscle and mediator release from human lung tissue and leukocytes.
研究了一种新合成的哒嗪酮衍生物NZ-107（4-溴-5-(3-乙氧基-4-甲氧基苄基氨基)-3(2H)-哒嗪酮）以及两种著名的抗哮喘药物氨来呫诺（口服活性类色甘酸钠药物）和色甘酸钠（DSCG）对体外分离的人气管平滑肌由抗原、组胺和白三烯C4（LTC4）诱导的收缩作用，以及对人肺组织和白细胞组胺释放的影响。在一些实验中，沙丁胺醇用作参考药物。NZ-107抑制抗原、组胺和LTC4诱导的气管平滑肌收缩。氨来呫诺和DSCG不影响每种刺激物引起的气管平滑肌收缩反应。沙丁胺醇抑制抗原诱导的气管平滑肌收缩。NZ-107、氨来呫诺、DSCG和沙丁胺醇均明显抑制抗原诱导的人肺组织组胺和LTC4释放。NZ-107和氨来呫诺抑制特应性人白细胞抗原诱导的组胺释放，但DSCG无此作用。白细胞介素-3预处理未改变抗原诱导的气管平滑肌收缩和肺组织组胺释放，但抗原或钙离子载体A 23187诱导的白细胞组胺释放明显增强。在两种刺激情况下，氨来呫诺均抑制白细胞介素-3诱导的白细胞组胺释放增强，但NZ-107和DSCG无此作用。这些数据表明，NZ-107基于抑制抗原诱导的人气管平滑肌收缩以及人肺组织和白细胞介质释放而具有强大的抗过敏作用。
