Ethenzamide Exerts Analgesic Effect at the Spinal Cord via Multiple Mechanisms of Action Including the 5HT2B Receptor Blockade in the Rat Formalin Test

Biological & Pharmaceutical Bulletin
Takato NikaidoAkiko Takaoka

Abstract

Ethenzamide (ETZ), an antipyretic analgesic categorized as a non-steroidal anti-inflammatory drug (NSAID), is widely used as an OTC drug in combination with other NSAIDs. However, its site of action and mechanism underlying its analgesic action have not yet been fully elucidated. In this study, we performed in vitro pharmacological assays to identify the mechanism underlying the analgesic action of ETZ, and also conducted the rat formalin test to investigate its analgesic effect and site of action. Of the 85 receptors, ion channels, transporters and enzymes tested, we found that ETZ binds to the 5-hydroxytryptamine (5HT)2B receptor in concentration-dependent manner with modest inhibitory effects on monoamine oxidase-A and transient potential vanilloid 1 channel. The 5HT2B receptor antagonist activity of ETZ was also confirmed in a cellular functional assay. Furthermore, the drug exerted no inhibitory effects on cycrooxygenase-1 and -2. In the rat formalin test, oral administration of ETZ significantly reduced the nociceptive responses of the second phase and also the number of c-Fos-expressing cells in the spinal dorsal horn, in a dose-dependent manner. Moreover, intrathecal administration of ETZ significantly reduced the nocic...Continue Reading

References

Nov 1, 1984·Journal of Pharmacobio-dynamics·J ShibasakiH Sasaki
Mar 16, 2004·Proceedings of the National Academy of Sciences of the United States of America·Dan LevyRami Burstein
Jun 17, 2006·Science·Hiroshi IkedaJürgen Sandkühler
Aug 10, 2007·Proceedings of the National Academy of Sciences of the United States of America·Colleen R McNamaraChristopher M Fanger
Sep 24, 2010·PloS One·Christophe MalletEdward D Högestätt
Jan 29, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Shih-Yuan LinWei-Hsin Sun
Apr 6, 2012·Pharmacology, Biochemistry, and Behavior·Claudia Cervantes-DuránVinicio Granados-Soto
Feb 5, 2013·The Journal of Pain : Official Journal of the American Pain Society·Ye CaoBarry J Sessle
Jan 27, 2015·Drug Development Research·Jorge B Pineda-FariasVinicio Granados-Soto
Jan 10, 2016·The Journal of Pain : Official Journal of the American Pain Society·Katherine A MifflinBradley J Kerr
Feb 29, 2016·Pharmacological Reports : PR·Claudia Cervantes-DuránVinicio Granados-Soto
Apr 30, 2016·Cephalalgia : an International Journal of Headache·Daniel Segelcke, Karl Messlinger
May 6, 2016·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Leonid P ShutovYuriy M Usachev
Oct 21, 2018·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Kasia K MarciszewskiLuke A Henderson

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