title: The mechanisms of action of nonsteroidal antiinflammatory drugs.
abstract: In mammalian species and in the oldest of multicellular animal forms, NSAIDs inhibit cell activation, apparently in the absence of effects on PG biosynthesis. Thus, an alternative hypothesis can be proposed to account for the antiinflammatory effects of these drugs. Clearly, at low doses aspirin and most of the newer NSAIDs inhibit the biosynthesis of PGs from arachidonic acid, and stable PGs have been shown to mediate fever, hyperalgesia, vasodilation (edema), and several interleukin-1-dependent responses. At high doses, however, aspirin, sodium salicylate, and the newer NSAIDs (at antiinflammatory doses) inhibit non-PG-dependent processes, such as the activity of a variety of enzymes, proteoglycan synthesis by chondrocytes, transmembrane ion fluxes, and chemoattractant binding. These effects are most likely due to the capacity of aspirin-like drugs to insert into the lipid bilayer of plasma membranes, where they disrupt normal signaling events and protein-protein interactions. The ability of NSAIDs to thereby inhibit the activation of inflammatory cells such as the neutrophil may contribute to the antiinflammatory properties of this class of drugs.
authors.affiliation: Department of Medicine, New York University Medical Center, NY 10016.
authors.forename: S
authors.initials: S
authors.lastname: Abramson
authors.forename: G
authors.initials: G
authors.lastname: Weissmann
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000188:drug therapy; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D010974:Platelet Aggregation / Q000187:drug effects; D011453:Prostaglandins / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000187:drug effects; D015290:Second Messenger Systems / Q000187:drug effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D011453:Prostaglandins; D011956:Receptors, Cell Surface