Nonsteroidal anti-inflammatory drugs active site

For a displacement interaction to become clinically important, a second mechanism usually operates sodium valproate can cause phenytoin toxicity because it both displaces phenytoin from its binding site on plasma albumin and inhibits its metabolism. Similarly aspirin and probenecid (and possibly other nonsteroidal anti-inflammatory drugs) displace the folic acid antagonist methotrexate from its protein-binding site and reduce its rate of active secretion by the renal tubules the result is serious methotrexate toxicity. 

The stmcture of the cyclooxygenase active site is very similar in both COX-1 and COX-2. However, there are two important structural differences between the two isoenzymes. Firstly, the active site of COX-2 is larger and more accommodating than that of COX-1, a feature that has been exploited in developing COX-2-specific nonsteroidal anti-inflammatory drugs (NSAID). Secondly, COX-1 exhibits negative allosterism at low concentrations of arachidonic acid. This feature may result in greater prostanoid synthesis by COX-2 under conditions of low arachidonic acid concentration (Smith et al, 2000). 

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