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01-06-2015 | Short Communication

µ-Opioid receptor activation by tramadol and O-desmethyltramadol (M1)

Authors: Kouichiro Minami, Yuka Sudo, Kanako Miyano, Robert S. Murphy, Yasuhito Uezono

Published in: Journal of Anesthesia | Issue 3/2015

Abstract

Tramadol has been used as an analgesic for several decades. µ-Opioid receptors (µORs) are the major receptors that mediate the analgesic effects of opioids. Although µORs have been thought to be one of the sites of action of tramadol, there has been no report that directly proves whether tramadol is an agonist of μOR or not. In this study, we examined the effects of tramadol and its main active metabolite O-desmethyltramadol (M1), on the function of µORs using Xenopus oocytes expressing cloned human µORs. The effects of tramadol and M1 were evaluated using the Ca²⁺-activated Cl⁻ current assay method for G_i/o-protein-coupled receptors by using a µOR fused to G_qi5 (µOR-G_qi5) in Xenopus oocytes. DAMGO [(d-Ala², N-MePhe⁴, Gly⁵-ol)-enkephalin] evoked Cl⁻ currents in oocytes expressing µOR-G_qi5 in a concentration-dependent manner. Tramadol and M1 also evoked Cl⁻ currents in the oocytes expressing µOR-G_qi5; however, relatively higher concentrations (compared to DMAGO) were necessary to induce such currents. Tramadol and M1 had a direct effect on µORs expressed in Xenopus oocytes. Although the monoamine uptake system and several types of ligand-gated ion channels are thought to be one of the targets for tramadol, tramadol-induced antinociception may be mediated at least in part, by the direct activation of µORs.

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Title: µ-Opioid receptor activation by tramadol and O-desmethyltramadol (M1)
Authors: Kouichiro Minami
Yuka Sudo
Kanako Miyano
Robert S. Murphy
Yasuhito Uezono
Publication date: 01-06-2015
Publisher: Springer Japan
Published in: Journal of Anesthesia / Issue 3/2015
Print ISSN: 0913-8668
Electronic ISSN: 1438-8359
DOI: https://doi.org/10.1007/s00540-014-1946-z

At a glance: The STEP trials

Springer Medicine

µ-Opioid receptor activation by tramadol and O-desmethyltramadol (M1)

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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