title: Comparative toxicities and analgesic activities of three monomethylated analogues of acetaminophen.
abstract: Three monomethylated derivatives of 4'-hydroxyacetanilide (acetaminophen) were prepared in order to compare their cytotoxic potential and analgesic activity with that of acetaminophen. Only 4'-hydroxy-N-methylacetanilide (N-methylacetaminophen) was devoid of cytotoxic effects to hepatic tissue of mice. Results of comparative tissue distribution studies and metabolism studies both in vivo and in vitro in mice indicate that the disposition of N-methylacetaminophen is similar to that of acetaminophen except that it is not oxidized to a toxic metabolite. In contrast, 3'-methyl-4'-hydroxyacetanilide (3-methylacetaminophen) is as hepatotoxic as acetaminophen in mice while 2'-methyl-4'-hydroxyacetanilide (2-methylacetaminophen) is less hepatotoxic. The analgesic potency of the analogues seems to parallel their hepatotoxic potential, and both activities parallel the oxidation potentials in this series of compounds.
mesh_terms: D000082:Acetaminophen / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity; D000698:Analgesia; D000818:Animals; D055598:Chemical Phenomena; D056486:Chemical and Drug Induced Liver Injury; D002621:Chemistry; D008297:Male; D008745:Methylation; D051379:Mice; D010084:Oxidation-Reduction; D014018:Tissue Distribution
chemical_list: D000082:Acetaminophen