title: Nitric oxide releasing acetaminophen (nitroacetaminophen).
abstract: The nitric oxide releasing derivative of acetaminophen (nitroacetaminophen) exhibits potent anti-inflammatory and anti-nociceptive activity in a variety of animal models. On a mol for mol basis nitroacetaminophen is some 3-20 times more potent than acetaminophen. Nitroacetaminophen exhibits little or no hepatotoxicity following administration in rat or mouse and indeed protects against the hepatotoxic activity of acetaminophen. Nitroacetaminophen does not affect blood pressure or heart rate of anaesthetised rats but has similar potency to acetaminophen as an anti-pyretic agent. The enhanced anti-inflammatory and anti-nociceptive activity of nitroacetaminophen and the reduced hepatotoxicity in these animal models is likely to be secondary to the slow release of nitric oxide from the molecule. As yet the precise molecular mechanism(s) underlying these actions of nitroacetaminophen are not clear. Evidence for inhibition of cytokine-directed formation of pro-inflammatory molecule production (e.g. COX-2, iNOS) by an effect on the NF-kappaB transduction system and/or nitrosylation (and thence inhibition) of caspase enzyme activity has been reported. Data described in this review indicate that the profile of pharmacological activity of nitroacetaminophen and acetaminophen are markedly different. The possibility that nitroacetaminophen could be an attractive alternative to acetaminophen in the clinic is discussed.
authors.affiliation: Centre for Cardiovascular Biology and Medicine, School of Biomedical Sciences, King's College, University of London, Guys Campus, Hodgkin Building, London SE1 1UL, UK. phillip.moore@kcl.ac.uk
authors.forename: P K
authors.initials: PK
authors.lastname: Moore
authors.forename: M
authors.initials: M
authors.lastname: Marshall
mesh_terms: D000082:Acetaminophen / Q000031:analogs & derivatives / Q000494:pharmacology*; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000633:toxicity; D004195:Disease Models, Animal; D005334:Fever / Q000188:drug therapy; D006801:Humans; D008099:Liver / Q000187:drug effects; D009566:Nitrates / Q000494:pharmacology*; D009569:Nitric Oxide / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D014652:Vascular Diseases / Q000188:drug therapy
chemical_list: D018712:Analgesics, Non-Narcotic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D009566:Nitrates; D009569:Nitric Oxide; D000082:Acetaminophen; C478738:4-(nitroxy)butanoic acid 4-acetylaminophenyl ester