Document Detail


Cyclooxygenase-2-selective inhibitors: translating pharmacology into clinical utility.
MedLine Citation:
PMID:  12086289     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Anti-inflammatory agents have been used for centuries, but only in the last few decades has medical science gained insight into the complex biologic roles of the primary mediators of inflammation, the eicosanoids and their derivatives. Detailed understanding of the prostaglandins and leukotrienes provides a framework for the treatment of pain, inflammation, and fever with aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs), but these agents have exacted a substantial side effect burden. The discovery of cyclooxygenase-2 (COX-2) has guided development of rationally designed therapeutic agents that have the benefits of older NSAIDs with reduced gastrointestinal toxicity. Elucidation of the structure of COX isoenzymes has been key in the development of coxibs, the COX-2-selective subset of NSAIDs. Methods to determine the degree of COX-2 selectivity have been refined and are indispensable for comparing the relative selectivity of these agents. This review summarizes some of the key aspects of COX biochemistry, structure, and function and the evolution of understanding the mechanism of action of COX-2-selective inhibitors. The clinical relevance of COX-1 compared with COX-2 inhibition is discussed to provide a framework upon which clinicians can better appreciate current and future therapeutic applications of coxibs.
Authors:
Bruce N Cronstein
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Publication Detail:
Type:  Comparative Study; Journal Article; Review    
Journal Detail:
Title:  Cleveland Clinic journal of medicine     Volume:  69 Suppl 1     ISSN:  0891-1150     ISO Abbreviation:  Cleve Clin J Med     Publication Date:  2002  
Date Detail:
Created Date:  2002-06-27     Completed Date:  2002-07-17     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8703441     Medline TA:  Cleve Clin J Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  SI13-9     Citation Subset:  IM    
Affiliation:
Division of Clinical Pharmacology, New York University School of Medicine, New York 10016, USA. cronsb01@med.nyu.edu
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MeSH Terms
Descriptor/Qualifier:
Anti-Inflammatory Agents, Non-Steroidal / pharmacology*,  therapeutic use
Cyclooxygenase 1
Cyclooxygenase 2
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors / pharmacology*,  therapeutic use
Humans
Isoenzymes / metabolism*
Membrane Proteins
Prostaglandin-Endoperoxide Synthases / metabolism*
Rheumatic Diseases / drug therapy,  enzymology
Sensitivity and Specificity
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents, Non-Steroidal; 0/Cyclooxygenase 2 Inhibitors; 0/Cyclooxygenase Inhibitors; 0/Isoenzymes; 0/Membrane Proteins; EC 1.14.99.1/Cyclooxygenase 1; EC 1.14.99.1/Cyclooxygenase 2; EC 1.14.99.1/PTGS1 protein, human; EC 1.14.99.1/PTGS2 protein, human; EC 1.14.99.1/Prostaglandin-Endoperoxide Synthases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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