BIOCHEMICAL PHARMACOLOGY OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS

Aspirin and conventional nonsteroidal anti-inflammatory drugs are nons elective inhibitors of cyclooxygenase-1 (COX-1) and COX-2 enzymes. Two classes of selective COX-2 inhibitors: (1) sulfonamides, such as L-74 5,337, and (2) tricyclic methyl sulfone derivatives, such as SC58125, have been developed. X-ray crystal structures of COX-1 and COX-2 have provided valuable information regarding the structural basis for their COX-2 selectivity. These compounds have less gastrointestinal complic ations in animal experiments. Their clinical efficacy and side-effects are being evaluated. Salicylate has very weak activity against either COX isoform and yet possesses anti-inflammatory actions. Recent studi es indicate that it suppresses the expression of genes involved in inf lammation. These activities may provide a plausible explanation for th e pharmacological dilemma and, furthermore, may represent novel mechan isms for controlling inflammation. (C) 1998 Elsevier Science Inc.