Mechanism of action of anti-inflammatory drugs.
Cyclooxygenase (COX) is the pivotal enzyme in prostaglandin biosynthesis. It exists in two isoforms, constitutive COX-1 (responsible for physiological functions) and inducible COX-2 (involved in inflammation). Inhibition of COX explains both the therapeutic effects (inhibition of COX-2) and side effects (inhibition of COX-1) of non-steroidal anti-inflammatory drugs (NSAIDs). A NSAID which selectively inhibits COX-2 is likely to retain maximal anti-inflammatory efficacy combined with less toxicity. The activity of a number of NSAIDs has been investigated in several test systems, showing that most of those marketed have higher activities against COX-1 or are equipotent against both isoforms. Adverse event data of marketed NSAIDs show a relationship between a poor safety profile and more potent inhibition of COX-1 relative to COX-2. There are several new non-steroidal COX-2 inhibitors in development. The most clinically advanced is meloxicam, which consistently demonstrates higher activity against COX-2 than COX-1 in several test systems.
Vane
J R
JR
William Harvey Research Institute, St Bartholomew's Hospital Medical College, London, UK.
Botting
R M
RM
D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D013256:Steroids / Q000009:adverse effects / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D013256:Steroids; D011451:Prostaglandin-Endoperoxide Synthases