Cyclooxygenase selectivity and NSAIDs: Cyclooxygenase-2 selectivity of etodolac (Lodine)
Cyclooxygenase selectivity and NSAIDs: Cyclooxygenase-2 selectivity of etodolac (Lodine)
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DOI：
10.1007/bf02668029
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发表时间：
1995-01-01
影响因子：
5.8
通讯作者：
Glaser, K. B.
中科院分区：
文献类型：
--
作者：
Glaser, K. B.
已经提出存在两种不同的环加氧酶（考克斯），考克斯-1和考克斯-2，其分别催化生理和促炎性胡萝卜素的产生。这在临床环境中可能是重要的，因为表现出考克斯-2选择性的NSAID可以抑制炎症反应而不引起考克斯-1介导的胃或肾并发症。目前，大多数NSAID抑制考克斯-1和考克斯-2酶。然而，在使用瞬时竞争性抑制和更临床相关的时间依赖性抑制方法的分离酶试验中，已经证明依托度酸（Lodine）优先抑制考克斯-2，选择性约为考克斯-1酶的10倍。依托度酸的这种考克斯-2选择性随后在细胞试验、人皮肤成纤维细胞和人全血中得到证实。此外，研究表明，代表新型NSAID的某些正在开发的化合物（例如NS-398和SC-58125）具有考克斯-2选择性。在目前市售的NSAID中，只有依托度酸始终表现出考克斯-2选择性，这可能部分解释依托度酸在动物和人体中的有利安全性特征。
It has been proposed that two distinct cyclooxygenase (COX) enzymes, COX-1 and COX-2 exist which catalyse the production of physiological and proinflammatory prostaglandins, respectively. This may be significant in the clinical setting, as an NSAID that demonstrates COX-2 selectivity could inhibit the inflammatory response without causing COX-1-mediated gastric or renal complications. Currently, most NSAIDs inhibit both COX-1 and COX-2 enzymes. However, in isolated enzyme assays using both instantaneous competitive inhibition and the more clinically relevant, time-dependent inhibition methods have demonstrated that etodolac (Lodine) preferentially inhibits COX-2, with an approximate 10-fold selectivity over the COX-1 enzyme. This COX-2 selectivity of etodolac has subsequently been confirmed in cellular assays, human dermal fibroblasts, and human whole blood. Also, the studies showed that certain compounds in development representing new classes of NSAIDs (e.g. NS-398 and SC-58125) had COX-2 selectivity. Of the currently marketed NSAIDs, only etodolac consistently demonstrates COX-2 selectivity, and this may, in part, explain the favourable safety profile of etodolac in animals and man.