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Development of Cyclooxygenases in the Treatment of Pain, Fever and Inflammation.


Cyclooxygenases (COXs) are enzymes that take part in a complex biosynthetic cascade that results in the conversion of polyunsaturated fatty acids (PUFAs) to prostaglandins (PGs) and thromboxanes (TXs). Their main role is to catalyze the transformation of AA into the intermediate PG-H2, which is the procursor of a variety of prostanoids (PTS) with diverse and potent biological actions. COXs have two main isoforms that are called COX-1 and COX-2 (as well as a COX-3). COX-1 is responsible for the synthesis of PG and TX in many types of cells, including the gastro-intestinal tract (GIT) and blood platelets. COX-2 plays a major role in PG biosynthesis in inflammatory cells and in the CNS. PG synthesis in these sites is a key factor in the development of inflammation and hyperalgesia. COX-2 inhibitors have analgesic and anti-inflammatory activity by blocking the transformation of AA into PG-H2 selectively. The impetus for development of selective COX-2 inhibitors was the adverse GIT side-effects of NSAIDs. Soon after the discovery of the mechanism of action of NSAIDs, strong indications emerged for alternative forms of COX. COX enzyme proved to be difficult to purify. The COX-2 enzyme was cloned.

Mohammad Asif

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