Indomethacin Pathway


Indomethacin, an NSAID, is a prostaglandin G/H synthase (a.k.a. cyclooxygenase or COX) inhibitor that acts on both prostaglandin G/H synthase 1 and 2 (COX-1 and -2). Prostaglandin G/H synthase catalyzes the conversion of arachidonic acid to a number of prostaglandins involved in fever, pain, swelling, inflammation, and platelet aggregation. Indomethacin antagonizes COX by binding to the upper portion of the active site, preventing its substrate, arachidonic acid, from entering the active site. Indomethacin, unlike other NSAIDs, also inhibits phospholipase A2, the enzyme responsible for releasing arachidonic acid from phospholipids. Indomethacin is more selective for COX-1 than COX-2, which accounts for its increased adverse gastric effects relative to other NSAIDs. COX-1 is required for maintaining the protective gastric mucosal layer. The analgesic, antipyretic and anti-inflammatory effects of indomethacin occur as a result of decreased prostaglandin synthesis.

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References

  1. Botting, R., & Botting, J. (2004). Cyclooxygenases. In S. Offermanns, & W. Rosenthal (Eds.). Encyclopedic reference of molecular pharmacology (pp. 279-283). Berlin, Germany: Springer.
  2. Breyer, R.M., & Breyer, M.D. (2004). Prostanoids. In S. Offermanns, & W. Rosenthal (Eds.). Encyclopedic reference of molecular pharmacology (pp. 752-757). Berlin, Germany: Springer.
  3. Geisslinger, G., & Lötsch, J. (2004). Non-steroidal anti-inflammatory drugs. In S. Offermanns, & W. Rosenthal (Eds.). Encyclopedic reference of molecular pharmacology (pp. 667-671). Berlin, Germany: Springer.
  4. Indomethacin (CPhA monograph). (2009). [Electronic version]. e-CPS. Retrieved August 15, 2009.