Abstract
The molecular identification of a second isoform of cyclooxygenase-2 (COX-2) led to a major investment by several pharmaceutical companies in the development of selective inhibitors. The central tenets of the rationale for developing selective COX-2 inhibitors are that prostaglandins that contribute to inflammation are derived from COX-2, whereas prostaglandins that are involved in normal physiological processes are derived from the constitutively expressed isoform COX-1. There is now considerable evidence that COX-2 is actually expressed constitutively in many tissues and performs important physiological functions. Thus, suppression of COX-2 with selective inhibitors should not be expected to be without some adverse consequences. Moreover, there is strong evidence that COX-1 contributes to inflammation and pain, so selective inhibition of COX-2 will not necessarily produce the same degree of efficacy that is seen with mixed inhibitors of COX-1 and COX-2.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
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Celecoxib
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Controlled Clinical Trials as Topic
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Cyclooxygenase 2
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Cyclooxygenase 2 Inhibitors
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Cyclooxygenase Inhibitors / adverse effects*
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Etodolac / adverse effects
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Gene Expression
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Humans
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Ibuprofen / adverse effects
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Indomethacin / adverse effects
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Isoenzymes / antagonists & inhibitors
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Isoenzymes / metabolism
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Isoenzymes / pharmacology
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Meloxicam
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Membrane Proteins
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Naproxen / adverse effects
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Nitrobenzenes / adverse effects
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Prostaglandin-Endoperoxide Synthases / biosynthesis
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Prostaglandin-Endoperoxide Synthases / metabolism*
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Prostaglandin-Endoperoxide Synthases / pharmacology
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Pyrazoles
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Sulfonamides / adverse effects
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Thiazines / adverse effects
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Thiazoles / adverse effects
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Cyclooxygenase 2 Inhibitors
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Cyclooxygenase Inhibitors
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Isoenzymes
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Membrane Proteins
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Nitrobenzenes
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Pyrazoles
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Sulfonamides
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Thiazines
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Thiazoles
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N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
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Etodolac
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Naproxen
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Cyclooxygenase 2
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PTGS2 protein, human
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Prostaglandin-Endoperoxide Synthases
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Celecoxib
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nimesulide
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Meloxicam
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Ibuprofen
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Indomethacin