Cyclo-oxygenase isoenzymes. How recent findings affect thinking about nonsteroidal anti-inflammatory drugs

The discovery of at least 2 cyclo-oxygenase (COX) isoenzymes, referred to as COX-1 and COX-2, has updated our knowledge of nonsteroidal anti-inflammatory drugs (NSAIDs). This has lead investigators to reconsider what can be awaited from this class of drugs. The 2 COX isoenzymes share structural and enzymatic similarities, but are specifically regulated at the molecular level and may be distinguished apart in their functions, although some physiological overlap between them does occur. The major goal in developing selective COX inhibitors is to improve NSAID tolerability. Classic NSAIDs preferentially inhibit COX-1 in vitro, but it appears hazardous to judge their gastrointestinal (GI) safety profile from these data. New compounds with a high selectivity for COX-2, especially those that are non-acidic, may be better tolerated in the GI tract. While these compounds also might have a potential use in various diseases such as colorectal cancer and neurodegenerative diseases of the Alzheimer type, the possible appearance of adverse effects, perhaps renally-related, must be taken into consideration. Finally, well-designed large clinical trials are required to adequately estimate both the promising therapeutic advantages that may be offered by highly selective NSAIDs, and the potential drawbacks that may be inherent with prolonged COX-2 inhibition.