Erman A, Azuri R, Raz A
Biochem Pharmacol. 1984 Jan 1;33(1):79-82. doi: 10.1016/0006-2952(84)90372-1.
Mepacrine was found to exert a dose-dependent inhibition of prostaglandin E2 synthesis in rabbit kidney medulla slices and in medullary microsomes. Mepacrine at 0.5 mM produced 90% inhibition of microsomal prostaglandin E2 biosynthesis from added arachidonic acid. This effect results from inhibition of medullary cyclooxygenase; the activities of the prostaglandin G2 hydroperoxidase and the prostaglandin H2 isomerases are unaffected. In experiments with medulla slices prelabelled with [14C]arachidonate, the effect of mepacrine on the inhibition of [14C]prostaglandin generation was significantly higher (2.5 to 3.5-fold) than its inhibition of [14C]arachidonate release. Hence, although mepacrine reduces prostaglandin production by decreasing the lipolytic release of arachidonate from medullary lipids, its inhibitory effect on prostaglandin cyclooxygenase activity is substantial and appears to contribute significantly to its overall inhibition of prostaglandin generation in kidney medulla. Mepacrine is thus not only a non-selective antilipolytic agent but also a potent cyclooxygenase inhibitor.
在兔肾髓质切片和髓质微粒体中，发现米帕林对前列腺素E2的合成具有剂量依赖性抑制作用。0.5 mM的米帕林对添加花生四烯酸后微粒体前列腺素E2的生物合成产生了90%的抑制作用。这种作用源于对髓质环氧化酶的抑制；前列腺素G2氢过氧化物酶和前列腺素H2异构酶的活性未受影响。在用[14C]花生四烯酸预标记的髓质切片实验中，米帕林对[14C]前列腺素生成的抑制作用显著高于（2.5至3.5倍）其对[14C]花生四烯酸释放的抑制作用。因此，尽管米帕林通过减少髓质脂质中花生四烯酸的脂解释放来降低前列腺素的产生，但其对前列腺素环氧化酶活性的抑制作用很大，并且似乎对其在肾髓质中对前列腺素生成的总体抑制作用有显著贡献。因此，米帕林不仅是一种非选择性抗脂解剂，也是一种有效的环氧化酶抑制剂。
