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

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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 Gi/o-protein-coupled receptors by using a µOR fused to Gqi5 (µOR-Gqi5) in Xenopus oocytes. DAMGO [(d-Ala2, N-MePhe4, Gly5-ol)-enkephalin] evoked Cl− currents in oocytes expressing µOR-Gqi5 in a concentration-dependent manner. Tramadol and M1 also evoked Cl− currents in the oocytes expressing µOR-Gqi5; 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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Authors and Affiliations

  1. Emergency Life Saving and Technique Tokyo, 4-5 Minamiosawa, Hachioji, Tokyo, 192-0364, Japan

    Kouichiro Minami

  2. Department of Molecular Pathology and Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan

    Yuka Sudo

  3. Division of Cancer Pathophysiology, National Cancer Center Research Institute, Tokyo, Japan

    Kanako Miyano & Yasuhito Uezono

  4. Center of Fundamental Education, University of Kitakyushu, Fukuoka, Japan

    Robert S. Murphy

Authors
  1. Kouichiro Minami
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  2. Yuka Sudo
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  3. Kanako Miyano
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  4. Robert S. Murphy
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  5. Yasuhito Uezono
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Correspondence to Kouichiro Minami.

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Minami, K., Sudo, Y., Miyano, K. et al. µ-Opioid receptor activation by tramadol and O-desmethyltramadol (M1) . J Anesth 29, 475–479 (2015). https://doi.org/10.1007/s00540-014-1946-z

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  • DOI: https://doi.org/10.1007/s00540-014-1946-z

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