Boneberg E M, Zou M H, Ullrich V
Faculty of Biology, University of Konstanz, Germany.
J Clin Pharmacol. 1996 Dec;36(12 Suppl):16S-19S.
Since the discovery of a cytokine-inducible isozyme of cyclooxygenase (COX-2), its pharmacologic inhibition has been the subject of recent investigations. These include tests for the selectivity of known nonsteroidal antiinflammatory drugs (NSAIDs) on the constitutive enzyme of cyclooxygenase (COX-1) compared with the inducible enzyme COX-2. The interesting question arose whether the R(-)- and S(+)-isomers exhibited different inhibitory potencies for ibuprofen. Results with isolated COX-1 and COX-2 isozymes confirmed the known higher efficacy of S(+)-compared with R(-)-ibuprofen. The R(-)-isomer is almost inactive in inhibiting COX-2. In addition, the S(+) form has a several times lower potency with COX-2 than with COX-1. These data were evaluated in platelets containing mainly the constitutive COX-1, with interleukin-1, pretreated, rat mesangial cells which almost exclusively express COX-2.
自从发现环氧化酶（COX-2）的细胞因子诱导同工酶以来，其药理抑制作用一直是近期研究的主题。这些研究包括测试已知非甾体抗炎药（NSAIDs）对组成型环氧化酶（COX-1）与诱导型酶COX-2的选择性。一个有趣的问题出现了，即R(-)-和S(+)-异构体对布洛芬是否表现出不同的抑制效力。分离的COX-1和COX-2同工酶的实验结果证实了已知的S(+)-布洛芬比R(-)-布洛芬具有更高的效力。R(-)-异构体在抑制COX-2方面几乎没有活性。此外，S(+)形式对COX-2的效力比对COX-1低几倍。这些数据在主要含有组成型COX-1的血小板以及经白细胞介素-1预处理的、几乎只表达COX-2的大鼠系膜细胞中进行了评估。
