Vane J R, Botting R M
William Harvey Research Institute, St Bartholomew's Hospital Medical College, London, UK.
Scand J Rheumatol Suppl. 1996;102:9-21. doi: 10.3109/03009749609097226.
Cyclooxygenase (COX) is the pivotal enzyme in prostaglandin biosynthesis. It exists in two isoforms, constitutive COX-1 (responsible for physiological functions) and inducible COX-2 (involved in inflammation). Inhibition of COX explains both the therapeutic effects (inhibition of COX-2) and side effects (inhibition of COX-1) of non-steroidal anti-inflammatory drugs (NSAIDs). A NSAID which selectively inhibits COX-2 is likely to retain maximal anti-inflammatory efficacy combined with less toxicity. The activity of a number of NSAIDs has been investigated in several test systems, showing that most of those marketed have higher activities against COX-1 or are equipotent against both isoforms. Adverse event data of marketed NSAIDs show a relationship between a poor safety profile and more potent inhibition of COX-1 relative to COX-2. There are several new non-steroidal COX-2 inhibitors in development. The most clinically advanced is meloxicam, which consistently demonstrates higher activity against COX-2 than COX-1 in several test systems.
环氧化酶（COX）是前列腺素生物合成中的关键酶。它以两种同工型存在，即组成型COX-1（负责生理功能）和诱导型COX-2（参与炎症反应）。抑制COX既解释了非甾体抗炎药（NSAIDs）的治疗作用（抑制COX-2），也解释了其副作用（抑制COX-1）。一种选择性抑制COX-2的NSAID可能会在保持最大抗炎效力的同时降低毒性。在多个测试系统中对多种NSAIDs的活性进行了研究，结果表明，大多数已上市的NSAIDs对COX-1的活性更高，或者对两种同工型的活性相当。已上市NSAIDs的不良事件数据显示，安全性较差与相对于COX-2更有效地抑制COX-1之间存在关联。目前有几种新型非甾体COX-2抑制剂正在研发中。临床进展最为显著的是美洛昔康，在多个测试系统中，它对COX-2的活性始终高于对COX-1的活性。
