Selective cyclooxygenase-2 inhibitors

Nonsteroidal anti-inflammatory drugs (NSAIDs) exert their clinical effects (both wanted and unwanted) by way of inhibition of prostaglandin synthesis by the cyclooxygenase (COX) enzyme. It has been discovered recently that COX exists in two isoforms: a constitutively expressed COX-1 subserves physiologic functions in gut and kidney, and an inducible COX-2 is upregulated at sites of inflammation, such as arthritic joints. Unlike conventional NSAIDs, which inhibit both isoforms, selective inhibitors of COX-2 would be expected to have clinical anti-inflammatory efficacy without significant toxicity. This article addresses the development of selective COX-2 inhibitors and their potential promise and pitfalls in the therapy of rheumatic disease.