alexa Mechanism of action of nonsteroidal anti-inflammatory drugs.
Pharmaceutical Sciences

Pharmaceutical Sciences

Journal of Pharmacognosy & Natural Products

Author(s): Vane JR, Botting RM

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Abstract Salicylic acid and salicylates, obtained from natural sources, have long been used as medicaments. Salicylic acid was chemically synthesized in 1860 and was used as an antiseptic, an antipyretic, and an antirheumatic. Almost 40 years later, aspirin was developed as a more palatable form of salicylate. Soon after, other drugs having similar actions to aspirin were discovered, and the group was termed the "aspirin-like drugs" (also now termed the nonsteroidal anti-inflammatory drugs [NSAIDs]). Twenty-five years ago, it was proposed that the mechanism of action of NSAIDs was through their inhibition of prostaglandin biosynthesis. Since then, there has been general acceptance of the concept that these drugs work by inhibition of the enzyme cyclo-oxygenase (COX), which we now know to have at least two distinct isoforms: the constitutive isoform, COX-1, and the inducible isoform, COX-2. COX-1 has clear physiologic functions. Its activation leads, for instance, to the production of prostacyclin, which when released by the endothelium is antithrombogenic and when released by the gastric mucosa is cytoprotective. COX-2, discovered 6 years ago, is induced by inflammatory stimuli and cytokines in migratory and other cells. It is therefore attractive to suggest that the anti-inflammatory actions of NSAIDs are due to inhibition of COX-2, whereas the unwanted side-effects, such as irritation of the stomach lining, are due to inhibition of COX-1. Drugs that have the highest COX-2 activity and a more favorable COX-2: COX-1 activity ratio will have a potent anti-inflammatory activity with fewer side-effects than drugs with a less favorable COX-2: COX-1 activity ratio. The identification of selective inhibitors of COX-2 will therefore lead to advances in therapy.
This article was published in Am J Med and referenced in Journal of Pharmacognosy & Natural Products

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