Selective cyclooxygenase-2 inhibitors: pharmacology, clinical effects and therapeutic potential

Since the discovery of a second isozyme of cyclooxygenase, COX-2, the field of prostaglandin and inflammation research has rapidly developed. It is becoming more evident that inhibition of COX-2 results in the analgesic and anti-inflammatory actions of non-steroidal anti-inflammatory drugs (NSAIDs), and that inhibition of COX-1 results in the adverse side-effects seen with these compounds. The mechanisms causing intestinal ulceration and renal toxicity are being elucidated, and large scale clinical trials with a preferential COX-2 inhibitor, meloxicam, and the first clinical results with highly selective COX-2 inhibitors, such as MK966 and celecoxib, support a superior benefit to risk ratio. In addition, important new areas where COX-2 expression is elevated, such as colonic cancer, have been identified and a role for COX-2 has also been proposed in Alzheimer's disease. Inhibition of COX-2 for these indications by selective COX-2 inhibitors may provide effective new therapies in the future.