A new approach to anti-inflammatory drugs.
A new approach to anti-inflammatory drugs.
复制标题
抗炎药物的新方法。
DOI：
10.1016/0006-2952(79)90651-8
复制
发表时间：
1979
影响因子：
5.8
通讯作者：
J. Vane
中科院分区：
文献类型：
--
作者：
G. Higgs;R. Flower;J. Vane
迄今为止测试的所有阿司匹林类药物均抑制前列腺素生物合成，但不能阻止花生四烯酸脂氧合酶生成羟基酸 12-l-羟基二十碳四烯酸 (HETE)。 HETE 对多形核白细胞具有趋化作用，并且无法抑制脂氧合酶，这可以解释为什么阿司匹林类药物在体内抗炎和抑制前列腺素合成的剂量下对白细胞迁移影响很小或没有影响。 3-Amino-1-[m-(三氟甲基)-苯基]-2-pyrazoline (BW755C) 在体外抑制花生四烯酸代谢的两条途径，并导致角叉菜胶诱导的大鼠爪水肿的剂量依赖性减少。 BW755C 还可以降低炎症渗出物中的前列腺素浓度，并且对白细胞迁移的影响明显大于吲哚美辛。因此，花生四烯酸环加氧酶（前列腺素合成酶）和脂氧合酶的双重抑制可能导致抗炎活性增加。
All aspirin-like drugs so far tested inhibit prostaglandin biosynthesis but do not prevent the generation of the hydroxy acid 12-l-hydroxyeicosatetraenoic acid (HETE) by arachidonate lipoxygenase. HETE is chemotactic for polymorphonuclear leukocytes, and the failure to inhibit lipoxygenase may explain why the aspirin-like drugs have little or no effect on leukocyte migration at doses which are both anti-inflammatory and inhibit prostaglandin synthesisin vivo. 3-Amino-1-[m-(trifluoromethyl)-phenyl]-2-pyrazoline (BW755C) inhibits both pathways of arachidonic acid metabolismin vitroand causes a dose-dependent reduction in carrageenin-induced oedema in the rat paw. BW755C also reduces prostaglandin concentration in inflammatory exudates and has a significantly greater effect on leukocyte migration than indomethacin. The dual inhibition of arachidonate cyclo-oxygenase (prostaglandin synthetase) and lipoxygenase could lead, therefore, to increased anti-inflammatory activity.