Authors: Takeuchi, K.; Tanaka, A.; Suzuki, K.; Mizoguchi, H.

Source: Current Pharmaceutical Design, Volume 7, Number 1, 1 January 2001 , pp. 49-69(21)

Publisher: Bentham Science Publishers

Abstract:

The use of nonsteroidal antiinflammatory drugs (NSAIDs) is associated with a wide array of alterations in gastrointestinal integrity and function. Various approaches have been taken to developing NSAIDs with reduced gastrointestinal toxicity, and few have been successfully reduced the incidence of adverse reactions. These include cyclooxygenase-2 (COX-2) selective inhibitors and nitric oxide (NO)-releasing NSAIDs. Especially, much has been written about the potential of COX-2 inhibitors as anti-inflammatory and analgesic agents that lack the gastrointestinal side effects of traditional NSAIDs. COX-2 expression is most evident at sites of inflammation, while COX-1 accounts for the majority of prostaglandin synthesis in the normal gastrointestinal tract. However, there are distinct examples of circumstances in which COX-2-derived prostaglandins play a role in the maintenance of gastrointestinal mucosal integrity, particularly when the mucosa is injured, and the delineation of COX-1 and COX-2 might not be quite as clear as has been suggested. On the other hand, the rational behind the NO-releasing NSAIDs is that the NO released from the derivatives will exert beneficial effects on the gastrointestinal mucosa. This approach has been successfully demonstrated to lessen the incidence of gastrointestinal damage and to promote the healing of gastric ulcers. The present article overviews the roles of COX and NO in housekeeping functions of the gastrointestinal mucosa in various circumstances, and the effects of gastrointestinal sparing NSAIDs, mainly COX-2 selective inhibitors and NO-releasing derivatives of NSAIDs, on the ulcerogenic and healing responses in the gastrointestinal mucosa of experimental animals.

Keywords: Gastrointestinal Sparing; Cyclooxygenase 2; Tumor necrosis factor; Cytoprotective action; Ulcerogenic Responses; NO releasing derivatives; Scavenges oxygen metabolites; Bacterial translocation; COX Inhibitors; Arthritic rat stomach

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1381612013398464

Publication date: 2001-01-01

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• Current Pharmaceutical Design publishes timely in-depth reviews covering all aspects of current research in rational drug design. Each issue is devoted to a single major therapeutic area. A Guest Editor who is an acknowledged authority in a therapeutic field has solicits for each issue comprehensive and timely reviews from leading researchers in the pharmaceutical industry and academia.
  
  Each thematic issue of Current Pharmaceutical Design covers all subject areas of major importance to modern drug design, including: medicinal chemistry, pharmacology, drug targets and disease mechanism.

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