Anesthesiology and Pain Medicine

Published by: Kowsar

Metabolism of AM404 From Acetaminophen at Human Therapeutic Dosages in the Rat Brain

Shun Muramatsu 1 , Seiji Shiraishi 1 , Kanako Miyano 1 , Yuka Sudo 1 , 2 , Akiko Toda 3 , Masayuki Mogi 3 , Mayumi Hara 4 , Akinobu Yokoyama 1 , 2 , Yoshihiko Kawasaki 4 , Mikio Taniguchi 4 and Yasuhito Uezono 1 , 5 , 6 , *
Authors Information
1 Division of Cancer Pathophysiology, National Cancer Center Research Institute, Tokyo, Japan
2 Division of Molecular Pathology and Metabolic Disease, Department of Pharmaceutical Sciences, Tokyo University of Science, Noda, Japan
3 Pharmacokinetics and Bioanalysis Center, Shin Nippon Biomedical Laboratories, Ltd., Wakayama, Japan
4 Division of Research and Development, Showa Yakuhin Kako Co., Ltd., Kawasaki, Japan
5 Division of Supportive Care Research, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Tokyo, Japan
6 Innovation Center for Supportive, Palliative and Psychosocial Care, National Cancer Center, Tokyo, Japan
Article information
  • Anesthesiology and Pain Medicine: February 01, 2016, 6 (1); e32873
  • Published Online: January 17, 2016
  • Article Type: Research Article
  • Received: September 1, 2015
  • Revised: October 10, 2015
  • Accepted: October 12, 2015
  • DOI: 10.5812/aapm.32873

To Cite: Muramatsu S, Shiraishi S, Miyano K, Sudo Y, Toda A, et al. Metabolism of AM404 From Acetaminophen at Human Therapeutic Dosages in the Rat Brain, Anesth Pain Med. 2016 ; 6(1):e32873. doi: 10.5812/aapm.32873.

Copyright © 2016, Iranian Society of Regional Anesthesia and Pain Medicine (ISRAPM). This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License ( which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.
1. Background
2. Objectives
3. Materials and Methods
4. Results
5. Discussion
  • 1. Bertolini A, Ferrari A, Ottani A, Guerzoni S, Tacchi R, Leone S. Paracetamol: new vistas of an old drug. CNS Drug Rev. 2006; 12(3-4): 250-75[DOI][PubMed]
  • 2. Prescott LF. Paracetamol: past, present, and future. Am J Ther. 2000; 7(2): 143-7[PubMed]
  • 3. Anderson BJ. Paracetamol (Acetaminophen): mechanisms of action. Paediatr Anaesth. 2008; 18(10): 915-21[DOI][PubMed]
  • 4. De Petrocellis L, Bisogno T, Davis JB, Pertwee RG, Di Marzo V. Overlap between the ligand recognition properties of the anandamide transporter and the VR1 vanilloid receptor: inhibitors of anandamide uptake with negligible capsaicin-like activity. . FEBS Lett. . 2000; 483(1): 52-6
  • 5. Hogestatt ED, Jonsson BA, Ermund A, Andersson DA, Bjork H, Alexander JP, et al. Conversion of acetaminophen to the bioactive N-acylphenolamine AM404 via fatty acid amide hydrolase-dependent arachidonic acid conjugation in the nervous system. J Biol Chem. 2005; 280(36): 31405-12[DOI][PubMed]
  • 6. Zygmunt PM, Chuang H, Movahed P, Julius D, Högestätt ED. The anandamide transport inhibitor AM404 activates vanilloid receptors. Eur J Pharmacol. 2000; 396(1): 39-42
  • 7. Beltramo M, Stella N, Calignano A, Lin SY, Makriyannis A, Piomelli D. Functional role of high-affinity anandamide transport, as revealed by selective inhibition. Science. 1997; 277(5329): 1094-7
  • 8. Fegley D, Kathuria S, Mercier R, Li C, Goutopoulos A, Makriyannis A, et al. Anandamide transport is independent of fatty-acid amide hydrolase activity and is blocked by the hydrolysis-resistant inhibitor AM1172. Proc Natl Acad Sci U S A. 2004; 101(23): 8756-61[DOI][PubMed]
  • 9. Mallet C, Barriere DA, Ermund A, Jonsson BA, Eschalier A, Zygmunt PM, et al. TRPV1 in brain is involved in acetaminophen-induced antinociception. PLoS One. 2010; 5(9)[DOI][PubMed]
  • 10. Dart RC, Bailey E. Does therapeutic use of acetaminophen cause acute liver failure? Pharmacotherapy. 2007; 27(9): 1219-30[DOI][PubMed]
  • 11. Sugiura T, Kondo S, Sukagawa A, Tonegawa T, Nakane S, Yamashita A, et al. Transacylase-mediated and phosphodiesterase-mediated synthesis of N-arachidonoylethanolamine, an endogenous cannabinoid-receptor ligand, in rat brain microsomes. Comparison with synthesis from free arachidonic acid and ethanolamine. Eur J Biochem. 1996; 240(1): 53-62[PubMed]
  • 12. Shinoda S, Aoyama T, Aoyama Y, Tomioka S, Matsumoto Y. Pharmacokinetics/pharmacodynamics of acetaminophen analgesia in Japanese patients with chronic pain. Biol Pharm Bull. 2007; 30(1): 157-61
Creative Commons License Except where otherwise noted, this work is licensed under Creative Commons Attribution Non Commercial 4.0 International License .

Search Relations:



Create Citiation Alert
via Google Reader

Readers' Comments