By by Helmut Buschmann (Editor), Thomas Christoph (Editor), Elmar Friderichs (Editor), Corinna Maul (Ed

ISBN-10: 3527304037

ISBN-13: 9783527304035

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Clinical Experiences with COX-2 Inhibitors A variety of clinical studies have shown the efficacy of the new COX-2 Inhibitors in several indications of pain and inflammation. Two large clinical studies have been performed in order to assess clinical efficacy and sideeffects of rofecoxib (VIGOR trial) and celecoxib (CLASS trial), respectively (Fitzgerald and Patrono, 2001). Both studies show an increased gastrointestinal safety profile compared to the standard medication, although only rofecoxib shows a statistically significant improvement.

Contrary to the classical NSAIDs, this new class of enzyme inhibitors lacks a carboxylic acid group, thus effecting COX-2 affinity by a different orientation within the enzyme without formation of a salt bridge in the hydrophobia channel of the enzyme. g. celecoxib and rofecoxib Modified, known NSAIDs to improve COX-2 selectivity: L-748780, L-761066, meloxicam, etodolac Antioxidative compounds 2 Cyclooxygenase Inhibition • 1,2-Diarylethylene derivatives (c/s-stilbenes) • Miscellaneous structures Diaryl- and Aryl-Heteroaryl Ether and Thioether Dlaryl- and aryl-heteroaryl ether and thioether compounds belong to the first generation of selective COX-2 Inhibitors (Fig.

Inhibition of pro-inflammatory transcription factors such as AP-1, NF-AT or NF-KB is thought to be the major action of glucocorticoids The role of glucocorticoids Another class of transcription-modulating drugs is the immunosuppressants such as cyclosporin A (CsA), which inhibit T cell activation and proliferation, events playing a central role in the immune response and therefore in the inflammatory process. CsA blocks transcriptional induction of cytokines by inhibiting the phosphatase calcineurin, and by the subsequent inhibition of the activation of NF-AT and NF-AT-dependent activation genes.

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Analgesics: From Chemistry and Pharmacology to Clinical Application by by Helmut Buschmann (Editor), Thomas Christoph (Editor), Elmar Friderichs (Editor), Corinna Maul (Ed

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