Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 388, Issue 10, pp 999–1007 | Cite as

What is the main mechanism of tramadol?

  • Kouichiro MinamiEmail author
  • Junichi Ogata
  • Yasuhito Uezono


Tramadol is an analgesic that is used worldwide for pain, but its mechanisms of action have not been fully elucidated. The majority of studies to date have focused on activation of the μ-opioid receptor (μOR) and inhibition of monoamine reuptake as mechanisms of tramadol. Although it has been speculated that tramadol acts primarily through activation of the μOR, no evidence has revealed whether tramadol directly activates the μOR. During the past decade, major advances have been made in our understanding of the physiology and pharmacology of ion channels and G protein-coupled receptor (GPCR) signaling. Several studies have shown that GPCRs and ion channels are targets for tramadol. In particular, tramadol has been shown to affect GPCRs. Here, the effects of tramadol on GPCRs, monoamine transporters, and ion channels are presented with a discussion of recent research on the mechanisms of tramadol.


Tramadol O-Desmethyl tramadol G protein-coupled receptor Ion channel Monoamine transporter 


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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Kouichiro Minami
    • 1
    • 2
    Email author
  • Junichi Ogata
    • 1
    • 2
  • Yasuhito Uezono
    • 2
  1. 1.Emergency Life Saving and Technique TokyoHachiojiJapan
  2. 2.Cancer Pathophysiology DivisionNational Cancer Center Research InstituteTokyoJapan

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