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甲氯芬那酸钠在体外是花生四烯酸级联反应中5-脂氧合酶和环氧化酶途径的抑制剂。

Meclofenamate sodium is an inhibitor of both the 5-lipoxygenase and cyclooxygenase pathways of the arachidonic acid cascade in vitro.

作者信息

Boctor A M, Eickholt M, Pugsley T A

出版信息

Prostaglandins Leukot Med. 1986 Aug;23(2-3):229-38. doi: 10.1016/0262-1746(86)90190-3.

Abstract

Meclofenamate sodium was compared to other nonsteroidal antiinflammatory drugs in terms of its potency to inhibit the formation of 5-HETE and LTB4 in human leukocytes and the formation of prostaglandin E2 in bovine seminal vesicles as measures of its ability to inhibit the 5-lipoxygenase and cyclooxygenase pathways of the arachidonic acid cascade. Meclofenamate sodium was about 2-4 times less potent than BW-755C in inhibiting 5-lipoxygenase enzyme activity and three times more potent than benoxaprofen, while naproxen, ibuprofen, and indomethacin showed IC50 greater than 100 microM. Meclofenamate sodium and indomethacin were the most potent inhibitors of the formation of PGE2 in bovine seminal vesicles followed by ibuprofen, naproxen, and benoxaprofen in this order. Meclofenamate sodium, like BW-755C, can be considered a dual inhibitor of 5-lipoxygenase and cyclooxygenase pathways of arachidonic acid cascade. This finding may explain in part the antiinflammatory activity of meclofenamate sodium.

摘要

就抑制人白细胞中5-羟二十碳四烯酸(5-HETE)和白三烯B4(LTB4)的形成以及牛精囊中前列腺素E2(PGE2)的形成而言,对甲氯芬那酸钠与其他非甾体抗炎药进行了比较,以此作为其抑制花生四烯酸级联反应中5-脂氧合酶和环氧化酶途径能力的衡量指标。在抑制5-脂氧合酶活性方面,甲氯芬那酸钠的效力比BW-755C低约2至4倍,比苯恶洛芬强三倍,而萘普生、布洛芬和吲哚美辛的半数抑制浓度(IC50)大于100微摩尔。在牛精囊中,甲氯芬那酸钠和吲哚美辛是PGE2形成的最有效抑制剂,其次依次是布洛芬、萘普生和苯恶洛芬。甲氯芬那酸钠与BW-755C一样,可被视为花生四烯酸级联反应中5-脂氧合酶和环氧化酶途径的双重抑制剂。这一发现可能部分解释了甲氯芬那酸钠的抗炎活性。

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