New non steroidal anti-inflammatory drugs: NO-releasing compounds and selective COX-2 inhibitors.

The use of non steroidal anti-inflammatory drugs as analgesic or anti-infla mmatory agents is primarily limited by their toxicity to the gastrointestin al tract. Two strategies have been developed recently in order to improve t he safety of these drugs. The first approach is the linking of a nitric oxi de-releasing moiety to the available compounds. The rationale is that nitri c oxide may prevent non steroidal anti-inflammatory drugs-induced ulceratio ns by preventing mucosal ischemia. The second approach is based on the disc overy of two isoforms (COX-1 and COX-2) of the cyclo-oxygenase enzyme. It w as hypothesized that the constitutively expressed COX-1 isoenzyme lends to the synthesis of prostaglandins with homeostatic functions whereas COX-2 is merely responsible for the production of prostaglandins mediating pain,fev er and inflammation. Accordingly, selective COX-2 inhibitors have been deve loped. Clinical trials indicate that these compounds are roughly as effecti ve as the available non steroidal anti-inflammatory agents without causing acute gastrointestinal damage. There is so,ne evidence that both COX-1 and COX-2 isoforms are involved in the production of prostaglandins associated with inflammation and homeostatic functions. Finally, the true benefit/risk ratio of these new non steroidal anti-inflammatory drugs remains to be ass essed. (C) 1999 Elsevier, Paris.