Non-steroidal anti-inflammatory drugs with selective inhibitory activity on cyclooxygenase 2. Interest and future prospects.

Introduction, - Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit the production of primary prostanoids by blocking the access of arachidonic aci d to the active site of the cyclooxygenases (COXs). Because the prostanoids produced by COX-I appear to play a physiological role (protection of the g astric mucosa, platelet aggregation, Vascular homeostasis, maintenance of r enal sodium-water balance) while those produced by COX-2 seem mainly to int ervene in the inflammatory response and in certain processes associated wit h cell proliferation, the hypothesis has been put forward that the NSAIDs t hat are selective COX-2 inhibitors should theoretically be capable of maint aining NSAID therapeutic properties but also have fewer adverse side effect s due to the maintenance of prostaglandin production at normal physiologica l levels. Current knowledge and key points. - The hypothesis of COX isoenzyme selecti vity has led to a proposed classification for COX inhibitors: 1) COX-I sele ctive inhibitors (low-dosage aspirin); 2) COX non-selective inhibitors (the majority of classified NSAIDs, which when administered over the long term, e.g., in cases of rheumatoid arthritis, cause duodenal ulcers in 20% of ca ses and gastric hemhorrage in 1-4% of cases/year); 3) COX-2 preferential in hibitors (meloxicam and nimesulide, which have fewer gastric side effects t han standard NSAIDs, but which are not risk-free at high doses); 4) COX-2 s elective inhibitors (celecoxib and rofecoxib). Preliminary clinical studies have shown that COX-2 selective inhibitors are as efficient as standard NS AIDs and have fewer adverse digestive side effects, thereby confirming the interest of this proposed classification. In the UK, the aforementioned stu dies have led to the commercialization of rofecoxib for the treatment of pa in and osteoarthritis, while celecoxib has been introduced in medical pract ice in the USA and other countries for the treatment of rheumatoid arthriti s and osteoarthritis. Future prospects and projects. - Various epidemiological and laboratory stu dies have indicated that NSAIDs may be able to reduce the risk of cancer (c olorectal cancer in particular) and Alzheimer's disease due to their inhibi tory activity on COXs, especially COX-2. The therapeutic contribution of CO X-2 specific inhibitors has to be more fully evaluated, particularly as the se agents could delay the healing of duodenal ulcers and interfere with sev eral COX-2-induced physiological functions. It is therefore suggested that until further information becomes available, this new class of NSAIDs shoul d be used with caution in certain patient populations. (C) 2000 Editions sc ientifiques et medicales Elsevier SAS.