Abstract
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 synthesis in vivo. 3-Amino-1-[ m-(trifluoromethyl)-phenyl]-2-pyrazoline (BW755C) inhibits both pathways of arachidonic acid metabolism in vitro and 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.
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