NEW INSIGHTS INTO THE THERAPEUTIC USE OF NITRIC OXIDE-DONATING NON-STEROIDAL ANTI-INFLAMMATORY DRUGS

Nitric oxide (NO), a radical with increased reactivity, diffusibility and instability plays an important role in the regulation of a wide range of physiological processes, including cellular immunity, angiogenesis, cardiac function, neurotransmission, and platelet aggregation. Numerous studies in recent decades have demonstrated the benefits and cytoprotective role of nitric oxide in different body systems. A modern experimental and clinical research direction is represented by the development of hybrids containing a NO donor coupled with a classical nonsteroidal anti-inflammatory agent, (NSAID) demonstrating an improved efficacy and tolerability compared to the administration of the drug alone in laboratory animals, in various experimental models. These agents are obtained by the ester linkage of a NO-releasing moiety to a standard NSAID, such as acetylsalicylic acid (NO-aspirin), ibuprofen (NO-ibuprofen), flurbiprofen (NO-flurbiprofen), naproxen (NO-naproxen), diclofenac (NO-diclofenac) and indomethacin (NO-indomethacin). Multiple pharmacological strategies regarding the release of NO from these hybrid NO-releasing compounds provide new insights into the pathogenesis and treatment of various pathological states, such as: inflammatory conditions, hypertension, atherosclerosis, neoplastic disease, degenerative diseases, colitis and bronchial asthma.