The Tramadol Metabolite O-Desmethyl Tramadol Inhibits Substance P-Receptor Functions Expressed in Xenopus Oocytes

DOI Web Site 被引用文献2件 参考文献28件
  • Minami Kouichiro
    Department of Anesthesiology and Critical Care Medicine, Jichi Medical University, Japan Division of Cancer Pathophysiology, National Cancer Center Research Institute, Japan
  • Yokoyama Toru
    Department of Anesthesiology and Critical Care Medicine, Jichi Medical University, Japan Division of Cancer Pathophysiology, National Cancer Center Research Institute, Japan
  • Ogata Junichi
    Department of Anesthesiology and Critical Care Medicine, Jichi Medical University, Japan
  • Uezono Yasuhito
    Division of Cancer Pathophysiology, National Cancer Center Research Institute, Japan

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Tramadol has been widely used as analgesic. O-Desmethyl tramadol (ODT) is one of the main metabolites of tramadol, having much greater analgesic potency than tramadol itself. Substance P receptors (SPR) are well known to modulate nociceptive transmission within the spinal cord. In this study, we investigated the effects of ODT on SPR expressed in Xenopus oocytes by examining SP-induced Ca2+-activated Cl− currents. ODT inhibited the SPR-induced Cl− currents at pharmacologically relevant concentrations. The protein kinase C (PKC) inhibitor bisindolylmaleimide I did not abolish the inhibitory effects of ODT on SP-induced Ca2+-activated Cl− currents. The results suggest that the tramadol metabolite ODT inhibits the SPR functions, which may be independent of activation of PKC-mediated pathways.

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