Chand N, Pillar J, Nolan K, Diamantis W, Sofia R D
Department of Pharmacology, Wallace Laboratories, Cranbury, N.J.
Int Arch Allergy Appl Immunol. 1989;90(1):67-70. doi: 10.1159/000235002.
Azelastine, an orally effective antiasthmatic agent, has been reported to inhibit antihistamine-resistant, leukotriene-mediated allergic bronchoconstriction in guinea pigs. This suggests that azelastine might act through inhibition of leukotriene (LT) C4/D4 synthesis. We have examined the effect of azelastine on allergic and nonallergic histamine secretion and LTC4 formation. Azelastine and the known 5-lipoxygenase inhibitors, nordihydroguaiaretic acid and AA-861, exerted concentration-dependent inhibition of allergic LTC4 formation in chopped lung tissue from actively sensitized guinea pigs and calcium ionophore A23187-stimulated LTC4 synthesis in mixed peritoneal cells from rats. Azelastine also produced concentration-dependent inhibition of allergic and nonallergic histamine secretion from rat peritoneal mast cells. The ability of azelastine to inhibit allergic and nonallergic histamine secretion and LTC4 generation may contribute to its mode of action and its therapeutic efficacy.
氮卓斯汀是一种口服有效的抗哮喘药物，据报道它能抑制豚鼠体内抗组胺药耐药的、白三烯介导的过敏性支气管收缩。这表明氮卓斯汀可能通过抑制白三烯（LT）C4/D4的合成发挥作用。我们研究了氮卓斯汀对过敏性和非过敏性组胺分泌以及LTC4形成的影响。氮卓斯汀以及已知的5-脂氧合酶抑制剂去甲二氢愈创木酸和AA-861，对主动致敏豚鼠切碎肺组织中的过敏性LTC4形成以及钙离子载体A23187刺激的大鼠混合腹膜细胞中的LTC4合成均有浓度依赖性抑制作用。氮卓斯汀还对大鼠腹膜肥大细胞的过敏性和非过敏性组胺分泌产生浓度依赖性抑制。氮卓斯汀抑制过敏性和非过敏性组胺分泌以及LTC4生成的能力可能有助于其作用方式和治疗效果。
