NEW-GENERATION NSAIDS - THE BENEFITS WITHOUT THE RISKS

Numerous attempts have been made over the past 50 years to develop non steroidal antiinflammatory drugs with reduced toxicity in the gastroin testinal tract and kidney. For the most part, these attempts have fail ed to significantly influence the incidence of clinically significant adverse effects (e.g., gastrointestinal bleeding, perforation). The de velopment of gastrointestinal- and renal-safe NSAIDs is complicated by the fact that both the beneficial (antiinflammatory, analgesic, antip yretic) and detrimental effects of NSAIDs are mechanistically linked t o the ability of these drugs to inhibit prostaglandin synthesis. Howev er, in recent years a number of new strategies have been undertaken to develop safer NSAIDs, and promising results in the laboratory setting suggest that at least some of these strategies will succeed. Selectiv e inhibitors of the inducible isoform of prostaglandin synthase and NS AID derivatives that release nitric oxide have been shown to exhibit t he desired effects of standard NSAIDs with greatly reduced toxicity. I n this review, the scientific foundations for a number of the strategi es for developing safer NSAIDs are reviewed, as are the data supportin g the claims that these drugs represent an advancement over existing N SAIDs.