کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1949131 1537719 2015 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Cyclooxygenase inhibitors: From pharmacology to clinical read-outs
ترجمه فارسی عنوان
مهار کننده های سیکلوکوکسیژناز: از فارماکولوژیک تا خواندن بالینی یک؟
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
چکیده انگلیسی


• Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit prostanoid biosynthesis.
• They comprise traditional (t) NSAIDs and selective inhibitors of COX-2 (coxibs).
• They are classified by assessing their impact on biomarkers of COX-1 and COX-2 activities.
• Use of these biomarkers allows a mechanistic interpretation of their clinical outcomes.

Acetylsalicylic acid (aspirin) is a prototypic cyclooxygenase (COX) inhibitor. It was synthesized serendipitously from a natural compound, i.e., salicylic acid, with known analgesic activity. This chemical modification, obtained for the first time in an industrial environment in 1897, endowed aspirin with the unique capacity of acetylating and inactivating permanently COX-isozymes. Traditional nonsteroidal anti-inflammatory drugs (tNSAIDs) were developed to mimic the pharmacological effects of aspirin, using aspirin-sensitive experimental models of pain and inflammation as the template for screening new chemical entities. Among the tNSAIDs, some were endowed with moderate COX- selectivity (e.g., diclofenac), but no studies of sufficient size and duration were performed to show any clinically relevant difference between different members of the class. Similarly, no serious attempts were made to unravel the mechanisms involved in the shared therapeutic and toxic effects of tNSAIDs until the discovery of COX-2. This led to characterizing their main therapeutic effects as being COX-2-dependent and their gastrointestinal (GI) toxicity as being COX-1-dependent, and provided a rationale for developing a new class of selective COX-2 inhibitors, the coxibs. This review will discuss the clinical pharmacology of tNSAIDs and coxibs, and the clinical read-outs of COX-isozyme inhibition. This article is part of a Special Issue entitled “Oxygenated metabolism of PUFA: analysis and biological relevance.”

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids - Volume 1851, Issue 4, April 2015, Pages 422–432
نویسندگان
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