Conversion of Acetaminophen to the Bioactive N-Acylphenolamine AM404 via Fatty Acid Amide Hydrolase-dependent Arachidonic Acid Conjugation in the Nervous System*

@article{Hgesttt2005ConversionOA,
  title={Conversion of Acetaminophen to the Bioactive N-Acylphenolamine AM404 via Fatty Acid Amide Hydrolase-dependent Arachidonic Acid Conjugation in the Nervous System*},
  author={E. H{\"o}gest{\"a}tt and B. J{\"o}nsson and Anna Ermund and D. Andersson and Henrik Bj{\"o}rk and J. Alexander and B. Cravatt and A. Basbaum and P. Zygmunt},
  journal={Journal of Biological Chemistry},
  year={2005},
  volume={280},
  pages={31405 - 31412}
}
  • E. Högestätt, B. Jönsson, +6 authors P. Zygmunt
  • Published 2005
  • Chemistry, Medicine
  • Journal of Biological Chemistry
  • Acetaminophen (paracetamol) is a popular domestic analgesic and antipyretic agent with a weak anti-inflammatory action and a low incidence of adverse effects as compared with aspirin and other non-steroidal anti-inflammatory drugs. Here we show that acetaminophen, following deacetylation to its primary amine, is conjugated with arachidonic acid in the brain and the spinal cord to form the potent TRPV1 agonist N-arachidonoylphenolamine (AM404). This conjugation is absent in mice lacking the… CONTINUE READING
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    References

    SHOWING 1-10 OF 87 REFERENCES
    Mechanism of acetaminophen inhibition of cyclooxygenase isoforms.
    • 151
    Determinants of the cellular specificity of acetaminophen as an inhibitor of prostaglandin H2 synthases
    • 205
    • PDF
    Anandamide transport is independent of fatty-acid amide hydrolase activity and is blocked by the hydrolysis-resistant inhibitor AM1172.
    • 211
    • PDF
    Biochemically based design of cyclooxygenase-2 (COX-2) inhibitors: facile conversion of nonsteroidal antiinflammatory drugs to potent and highly selective COX-2 inhibitors.
    • 207
    • PDF
    Ibuprofen inhibits the metabolism of the endogenous cannabimimetic agent anandamide.
    • 47
    Supersensitivity to anandamide and enhanced endogenous cannabinoid signaling in mice lacking fatty acid amide hydrolase
    • 1,142
    • PDF
    Cyclooxygenase Isozymes: The Biology of Prostaglandin Synthesis and Inhibition
    • 1,410
    • PDF