Perspectives in Nonsteroidal Anti‐inflammatory Agents

Among numerous nonsteroidal anti‐imflammatory agents synthesized in the past few years, various analogs of indomethacin, phenylacetic acid and heteroarylacetic acid have reached the stage of clinical evaluation. Their biochemical mechanisms of action are exemplified by the broad activity profile of indomethacin which includes inhibition of mediators and enzymes, effects on cell membranes, and, most recently, inhibition of prostaglandin biosynthesis. The importance of pharmacodynamic properties to clinical efficacy was clearly demonstrated in some cases. Several candidates were eliminated because of their side‐effects. A group of α‐methylarylacetic acids showed a high degree of stereospecificity in their potency and metabolisms in vivo , as well as inhibition of prostaglandin synthetase and albumin binding in vitro . Extrinsic Cotton effect provides a sensitive technique in the study of interactions of these drugs with biopolymers. Competitive binding and antagonistic interactions between nonsteroidal drugs, particularly salicylate, were observed in vitro and in vivo . Progress in salicylate research was marked by the synthesis of flufenisal as a new derivative with enhanced potency and longer duration of action. Several fenamate analogs and new chemical types have shown promise in preliminary clinical trials. Various immunological approaches are under investigation for the treatment of rheumatoid arthritis. Newer concepts are still needed to achieve more effective control of arthritic disorders.