The therapeutic potential of NO-NSAIDs.
NSAIDs, including those that are selective for cyclooxygenase-2, are among the most widely used drugs. However, these drugs produce significant side effects in the gastrointestinal and cardiorenal systems, which greatly limit their utility. In recent years, a new type of anti-inflammatory agent has been developed that appears to offer significant advantages over conventional and Cox-2-selective NSAIDs. No-NSAIDs are derivatives of conventional NSAIDs, which are able to release nitric oxide over prolonged periods of time. The combination of balanced inhibition of the two main isoforms of COX with controlled release of nitric oxide yields a series of drugs that exert anti-inflammatory and analgesic activities in a wide range of settings, and have markedly reduced gastrointestinal and cardiorenal toxicity. Recent clinical trials of NO-NSAIDs have provided a 'proof of concept' that is completely consistent with pre-clinical characterization of these compounds.
Wallace
John L
JL
f Pharmacology and Therapeutics, University of Calgary, Alberta, Canada. wallacej@ucalgary.ca
Del Soldato
Piero
P
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000139:chemically induced; D002986:Clinical Trials as Topic; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D007674:Kidney Diseases / Q000139:chemically induced; D008565:Membrane Proteins; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D011451:Prostaglandin-Endoperoxide Synthases
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases