Acetaminophen

Acetaminophen is an analgesic and antipyretic compound.{42476,42477} Unlike many NSAIDs, which inhibit both COX-1 and COX-2, early studies suggested that acetaminophen is a poor inhibitor of both isoforms.{1287,8427} However, it does inhibit COX-2 by 83% and COX-1 by 56% in human blood ex vivo, albeit at a high 1,000 mg dose, with IC50 values of 25.8 and 113.7 µM, respectively.{29484} Acetaminophen is enzymatically and non-enzymatically converted to several reactive metabolites that contribute to adverse or indirect effects, including liver injury.{29483,13644,27991} At toxic doses, the acetaminophen metabolite N-acetyl-4-benzoquinone imine (NAPQI; Item No. 16115) depletes glutathione reserves in the liver, leading to an accumulation of NAPQI and subsequent hepatocyte necrosis.{7361} Acetaminophen decreases glutathione levels and reduces glutathione peroxidase activity in mice when administered at a dose of 250 mg/kg and induces ferroptotic cell death in primary mouse hepatocytes, an effect that can be blocked by the ferroptosis inhibitor ferrostatin-1 (Item No. 17729).{42478,42479} Acetaminophen has analgesic and antipyretic properties in animal models.{42476,42477}