The main target of acetaminophen application is bifunctional enzyme--prostaglandin endoperoxide H2 synthase (PGHS)--which has cyclo-oxygenase and peroxidase activities and synthesizes initial intermediates in prostanoid synthesis. The reaction catalyzed by PGHS is radical-based and it is initiated and then maintained by the constant presence of peroxides especially peroxynitrate, which generate so-called "peroxide tone" in the enzyme surrounding. Currently it is known that inhibitory effect of acetaminophen on PGHS activity is directly connected with the elimination of "peroxide tone". High concentrations of reactive compounds (e.g. peroxynitrate and lipid peroxides)--produced by cellular defending mechanism at inflammatory sites--significantly decrease inhibitory impact of acetaminophen on PGHS activity. Such observation allows explanation of weak antiinflammatory effect of acetaminophen together with its strong analgesic and antipyretic properties.
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