JOURNAL HOME CME HOME THIS MONTH PAST ISSUES ETOC COLLECTIONS AUTHORS REVIEWERS EDITORIAL BOARD FEEDBACK RSS HELP
		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (15) Citing Articles via Google Scholar Google Scholar Articles by Shiga, Y. Articles by Shigematsu, A. Search for Related Content PubMed PubMed Citation Articles by Shiga, Y. Articles by Shigematsu, A. Related Collections Pharmacology

---

ANESTHETIC PHARMACOLOGY

The Inhibitory Effects of Tramadol on Muscarinic Receptor-Induced Responses in Xenopus Oocytes Expressing Cloned M₃ Receptors

Yousuke Shiga, MD^*, Kouichiro Minami, MD PhD^*, Munehiro Shiraishi, MD^*, Yasuhito Uezono, MD PhD, Osamu Murasaki, MD, Muneshige Kaibara, MD PhD, and Akio Shigematsu, MD PhD^*

*Department of Anesthesiology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu; and Department of Pharmacology II, Nagasaki University, School of Medicine, Nagasaki, Japan

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

Tramadol is a widely used analgesic, but its mechanism of action is not completely understood. Muscarinic receptors are involved in neuronal function in the brain and autonomic nervous system, and much attention has been paid to these receptors as targets of analgesic drugs in the central nervous system. In this study, we investigated the effects of tramadol on type-3 muscarinic (M₃) receptors using the Xenopus oocyte expression system. Tramadol (10 nM–100 µM) inhibited acetylcholine-induced currents in oocytes expressing M₃ receptor. Although GF109203X, a protein kinase C inhibitor, increased the basal current, it had little effect on the inhibition of acetylcholine-induced currents by tramadol. Moreover, tramadol inhibited the specific binding sites of [³H]quinuclidinyl benzilate. These findings suggest that tramadol at clinically relevant concentrations inhibits M₃ function via quinuclidinyl benzilate-binding sites. This may explain the modulation of neuronal function and the anticholinergic effects of tramadol.

IMPLICATION. Muscarinic receptors are involved in neuronal function and are targets of analgesic drugs. We here report that tramadol inhibits type-3 muscarinic receptors function via quinuclidinyl benzilate-binding sites at clinically relevant concentrations. These findings may explain the modulation of neuronal function and the anticholinergic effects of tramadol.

This article has been cited by other articles:

				A. Agarwal, G. Yadav, D. Gupta, P. K. Singh, and U. Singh Evaluation of intra-operative tramadol for prevention of catheter-related bladder discomfort: a prospective, randomized, double-blind study Br. J. Anaesth., October 1, 2008; 101(4): 506 - 510. [Abstract] [Full Text] [PDF]

				I.-W. Shin, J.-T. Sohn, K.-E. Park, K. C. Chang, J.-Y. Choi, H.-K. Lee, and Y.-K. Chung A supraclinical dose of tramadol stereoselectively attenuates endothelium-dependent relaxation in isolated rat aorta. Anesth. Analg., August 1, 2006; 103(2): 366 - 71, table of contents. [Abstract] [Full Text] [PDF]

				M. Elhakim, W. A. El-Megid, A. Metry, A. El-hennawy, and K. El-Queseny Analgesic and antacid properties of i.m. tramadol given before Caesarean section under general anaesthesia Br. J. Anaesth., December 1, 2005; 95(6): 811 - 815. [Abstract] [Full Text] [PDF]

				M. Nakamura, K. Minami, Y. Uezono, T. Horishita, J. Ogata, M. Shiraishi, T. Okamoto, T. Terada, and T. Sata The Effects of the Tramadol Metabolite O-Desmethyl Tramadol on Muscarinic Receptor-Induced Responses in Xenopus Oocytes Expressing Cloned M1 or M3 Receptors Anesth. Analg., July 1, 2005; 101(1): 180 - 186. [Abstract] [Full Text] [PDF]

				K. Minami, J. Ogata, T. Horishita, M. Shiraishi, T. Okamoto, T. Sata, and A. Shigematsu Intramuscular tramadol increases gastric pH during anesthesia: [L'administration intramusculaire du tramadol augmente le pH gastrique pendant l'anesthesie] Can J Anesth, June 1, 2004; 51(6): 545 - 548. [Abstract] [Full Text] [PDF]

				J. Ogata, K. Minami, Y. Uezono, T. Okamoto, M. Shiraishi, A. Shigematsu, and Y. Ueta The Inhibitory Effects of Tramadol on 5-Hydroxytryptamine Type 2C Receptors Expressed in Xenopus Oocytes Anesth. Analg., May 1, 2004; 98(5): 1401 - 1406. [Abstract] [Full Text] [PDF]

				M. Shiraishi, K. Minami, I. Shibuya, Y. Uezono, J. Ogata, T. Okamoto, O. Murasaki, M. Kaibara, Y. Ueta, and A. Shigematsu The Inhibitory Effects of Alphaxalone on M1 and M3 Muscarinic Receptors Expressed in Xenopus Oocytes Anesth. Analg., August 1, 2003; 97(2): 449 - 455. [Abstract] [Full Text] [PDF]

				T. Okamoto, K. Minami, Y. Uezono, J. Ogata, M. Shiraishi, A. Shigematsu, and Y. Ueta The Inhibitory Effects of Ketamine and Pentobarbital on Substance P Receptors Expressed in Xenopus Oocytes Anesth. Analg., July 1, 2003; 97(1): 104 - 110. [Abstract] [Full Text] [PDF]

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