Calhoun W, Chang J, Carlson R P
Division of Experimental Therapeutics, Wyeth Laboratories, Inc., Philadelphia, PA 19101.
Agents Actions. 1987 Aug;21(3-4):306-9. doi: 10.1007/BF01966499.
Zymosan, carrageenan, arachidonic acid and platelet activating factor (PAF) were used to induce inflammation (edema) in the paws of mice. Antiinflammatory drugs (e.g., BW 755C and indomethacin) as well as cyproheptadine (mediator antagonist), theophylline (phosphodiesterase inhibitor) and guanabenz (alpha adrenoceptor agonist) showed the greatest efficacy in the carrageenan and zymosan models. Nonsteroidal antiinflammatory (NSAIDs) agents showed greater activity in the arachidonic acid (AA) paw edema model than the dual 5-lipoxygenase (LO)/cyclooxygenase (CO) inhibitors. The PAF model was insensitive to NSAIDs but showed some activity with drugs possessing inhibitory 5-LO activity (e.g., phenidone, BW 755C) and the mediator antagonist, cyproheptadine. Suramin, a complement inhibitor, as expected, was active only against zymosan-induced edema. In conclusion, the inhibitory activities of dual 5-LO/CO inhibitors and NSAIDs were not different in the zymosan, carrageenan and AA edema models in the mouse; however, some selectivity for 5-LO inhibitors was observed in the PAF model.
用酵母聚糖、角叉菜胶、花生四烯酸和血小板活化因子(PAF)诱导小鼠爪部炎症(水肿)。抗炎药物(如BW 755C和吲哚美辛)以及赛庚啶(介质拮抗剂)、茶碱(磷酸二酯酶抑制剂)和胍那苄(α肾上腺素能受体激动剂)在角叉菜胶和酵母聚糖模型中显示出最大疗效。非甾体抗炎药(NSAIDs)在花生四烯酸(AA)爪部水肿模型中比双重5-脂氧合酶(LO)/环氧化酶(CO)抑制剂表现出更强的活性。PAF模型对NSAIDs不敏感,但对具有抑制5-LO活性的药物(如非那吡啶、BW 755C)和介质拮抗剂赛庚啶有一定活性。如预期的那样,补体抑制剂苏拉明仅对酵母聚糖诱导的水肿有活性。总之,双重5-LO/CO抑制剂和NSAIDs在酵母聚糖、角叉菜胶和AA水肿模型中的抑制活性在小鼠中没有差异;然而,在PAF模型中观察到对5-LO抑制剂有一定的选择性。