Cyclooxygenase-1 and Cyclooxygenase-2 Knockout Mice Provide Insights into Beneficial and Adverse Effects of Nonsteroidal Anti-Inflammatory Drugs

Two isoforms of cyclooxygenase (COX-1 and COX-2) are known and both catalyze the first committed step in the pathway leading to the production of prostaglandins (PGs), i.e., PGE2, PGD2, PGI2, PGF2, and thromboxane A2 (1) Both isoforms are biological targets for the widely used class of medicines known as nonsteroidal anti-inflammatory drugs (NSAIDs); and NSAIDs are believed to cause their biological effects by effectively reducing PG production. However, because studies indicated that COX-1 and COX-2 have different physiological functions (2), NSAIDs with increased isoform selectivity have been developed. As COX-1 was the isoform believed to generate PGs associated with house keeping functions, and COX-2 was the isoform believed to produce PGs associated with the development of several diseases, the emphasis has been to develop NSAIDs with increased selectivity for COX-2.