Cyclooxygenase and nitric oxide systems in the gut as therapeutic targets for safer anti-inflammatory drugs.

William Harvey Research Institute, Bart's and The London, Queen Mary's School of Medicine, Charterhouse Square, London EC1M 6BQ, UK. b.j.whittle@qmul.ac.uk

Current opinion in pharmacology 2004 Dec

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After a decade of intense pharmacological and drug development activity by the pharmaceutical industry, compounds derived from two key strategies for reducing gastrointestinal effects of non-steroidal anti-inflammatory drugs (NSAIDs) have been subjected to rigorous clinical appraisal. Despite the undoubted therapeutic and commercial success of the selective cyclooxygenase (COX)-2 inhibitors, known as the coxibs, with second-generation compounds already approved and launched, some concerns over their full gastrointestinal profile still linger, while the cardiovascular safety of this class has become a key issue. Likewise, Phase II evaluation of compounds incorporating a nitric oxide (NO)-donating moiety into standard NSAIDs (the NO-NSAIDs or CINODs) has created recent controversy over the full clinical profile of these compounds. Other approaches such as NO-COX-2 inhibitors and dual COX-lipoxygenase inhibitors are already warranting interest. It might therefore be too early to predict the eventual winning strategy for safer anti-inflammatory drugs.

Citation

Brendan J R Whittle. Cyclooxygenase and nitric oxide systems in the gut as therapeutic targets for safer anti-inflammatory drugs. Current opinion in pharmacology. 2004 Dec;4(6):538-45