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PAIN MEDICINE

The Effects of Tramadol and Its Metabolite on Glycine, -Aminobutyric Acid_A, and N-Methyl-d-Aspartate Receptors Expressed in Xenopus Oocytes

Department of Anesthesiology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan

Address correspondence and reprint requests to Koji Hara, MD, PhD, Department of Anesthesiology, University of Occupational and Environmental Health School of Medicine, 1-1, Iseigaoka, Yahatanishiku, Kitakyushu 807-8555, Japan. Address e-mail to kojihara{at}med.uoeh-u.ac.jp.

We assessed the effects of tramadol, a centrally acting analgesic, and its major metabolite, on neurotransmitter-gated ion channels. Tramadol binds to µ-opioid receptors with low affinity and inhibits reuptake of monoamines in the central nervous system. These actions are believed to primarily contribute to its antinociceptive effects. However, little is known about other sites of tramadol's action. We tested the effects of tramadol and its M1 metabolite (0.1–100 µM) on human recombinant neurotransmitter-gated ion channels, including glycine, -aminobutyric acid_A (GABA_A), and N-methyl-d-aspartate (NMDA) receptors, expressed in Xenopus oocytes. Tramadol and M1 metabolite did not have any effects on glycine receptors. GABA_A receptors were significantly inhibited only at large concentrations (100 µM). NMDA receptors were inhibited in a concentration-dependent manner. Tramadol and M1 metabolite inhibited the glutamate-concentration response curve without changing the half-maximal effective concentration or the Hill coefficient, indicating a noncompetitive inhibition. This study suggests that glycine receptors do not provide the antinociceptive effect of tramadol and that the inhibition of GABA_A receptors at large concentration might correlate with convulsions. The inhibitory effect on NMDA receptors may contribute to the antinociceptive effect of tramadol at relatively large concentrations.

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999