Cyclo‐oxygenase‐2: pharmacology, physiology, biochemistry and relevance to NSAID therapy

• Published in: British journal of pharmacology Vol. 128; no. 6; pp. 1121 - 1132
• Main Authors: Mitchell, Jane A, Warner, Timothy D
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-11-1999; Nature Publishing
• Subjects: Alzheimer Disease - drug therapy; Alzheimer Disease - enzymology; Analytical, structural and metabolic biochemistry; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; celecoxib; Cyclooxygenase 2; Cyclo‐oxygenase‐2; Enzymes and enzyme inhibitors; Fundamental and applied biological sciences. Psychology; Humans; inflammation; Inflammation - drug therapy; Inflammation - enzymology; Isoenzymes - drug effects; Isoenzymes - metabolism; Isoenzymes - physiology; Medical sciences; Membrane Proteins; Neoplasms - drug therapy; Neoplasms - enzymology; nonsteroidal anti‐inflammatory drugs; Oxidoreductases; Pharmacology. Drug treatments; Prostaglandin-Endoperoxide Synthases - drug effects; Prostaglandin-Endoperoxide Synthases - metabolism; Prostaglandin-Endoperoxide Synthases - physiology; prostaglandins; Review; rofecoxib; Human; Prostaglandin-endoperoxide synthase; Pathophysiology; Prostaglandin; Enzyme; Gene product; Enzyme inhibitor; Inflammation; Pharmacology; Review; Gene expression; Biological activity; Non steroidal antiinflammatory agent; Physiology; Oxidoreductases
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0702897

Cyclo‐oxygenase is expressed in cells in two distinct isoforms. Cyclo‐oxygenase‐1 is present constitutively whilst cyclo‐oxygenase‐2 is expressed primarily after inflammatory insult. The activity of cyclo‐oxygenase‐1 and ‐2 results in the production of a variety of potent biological mediators (the prostaglandins) that regulate homeostatic and disease processes. Inhibitors of cyclo‐oxygenase include the nonsteroidal anti‐inflammatory drugs (NSAIDs) aspirin, ibuprofen and diclofenac. NSAIDs inhibit cyclo‐oxygenase‐2 at the site of inflammation, to produce their therapeutic benefits, as well as cyclo‐oxygenase‐1 in the gastric mucosa, which produces gastric damage. Most recently selective inhibitors of cyclo‐oxygenase‐2 have been developed and introduced to man for the treatment of arthritis. Moreover, recent epidemiological evidence suggests that cyclo‐oxygenase inhibitors may have important therapeutic relevance in the prevention of some cancers or even Alzheimer's disease. This review will discuss how the new advancements in NSAIDs research has led to the development of a new class of NSAIDs that has far reaching implications for the treatment of disease.
British Journal of Pharmacology (1999) 128, 1121–1132; doi:10.1038/sj.bjp.0702897