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 Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (17) Citing Articles via Google Scholar Google Scholar Articles by Nishiyama, T. Articles by Yamaguchi, T. Search for Related Content PubMed PubMed Citation Articles by Nishiyama, T. Articles by Yamaguchi, T.

---

REGIONAL ANESTHESIA AND PAIN MANAGEMENT

The Spinal Antinociceptive Effects of a Novel Competitive AMPA Receptor Antagonist, YM872, on Thermal or Formalin-Induced Pain in Rats

Tomoki Nishiyama, MD, PhD^*,, Laszlo Gyermek, MD, PhD^*, Chingmuh Lee, MD^*, Sachiko Kawasaki-Yatsugi, BS, and Tokio Yamaguchi, PhD

*Department of Anesthesiology, Harbor-University of California, Los Angeles Medical Center, Torrance, California; Department of Anesthesiology, The University of Tokyo, Tokyo; and Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Tsukuba, Japan

Address correspondence and reprint requests to Tomoki Nishiyama, MD, PhD, Department of Anesthesiology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

-Amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor antagonists have spinally mediated analgesic effects on acute nociception; however, their current formulations are not water-soluble and have toxic side effects. A new competitive AMPA antagonist, YM872 (2,3-dioxo-7-[1H-imidazol-1-yl]-6-nitro-1,2,3,4-tetrahydro-1-quinoxalinyl acetic acid) is water-soluble and may have fewer side effects. The purpose of this study was to investigate the analgesic effects of YM872 on both acute thermal and irritant-induced pain. Sprague-Dawley rats were implanted with chronic lumbar intrathecal catheters and were tested for their tail withdrawal response by the tail flick test and for their paw flinches by formalin injection after the intrathecal administration of YM872. The tail flick latency increased dose-dependently with a 50% effective dose (ED₅₀) value of 1.0 µg. The number of flinches in both Phase 1 and Phase 2 of the formalin test decreased with increasing dose of YM872. ED₅₀ values were 0.24 µg in Phase 1 and 0.21 µg in Phase 2. YM872 10 and 30 µg induced motor disturbance and flaccidity. In rats, the intrathecal administration of YM872 had analgesic effects on both acute thermal and formalin-induced nociceptions. Transient motor disturbance and flaccidity occurred only with large doses. YM872 may have potential in the clinical management of both acute and chronic pain.

Implications: A novel -amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor antagonist, YM872, may have an analgesic effect on both acute and chronic pain when administered intrathecally.

This article has been cited by other articles:

				Y. Koizumi, M. Matsumoto, A. Yamashita, S. Tsuruta, T. Ohtake, and T. Sakabe The effects of an AMPA receptor antagonist on the neurotoxicity of tetracaine intrathecally administered in rabbits. Anesth. Analg., March 1, 2006; 102(3): 930 - 936. [Abstract] [Full Text] [PDF]

				T. Nishiyama, L. Gyermek, C. Lee, S. Kawasaki-Yatsugi, T. Yamaguchi, and K. Hanaoka The Analgesic Interaction Between Intrathecal Clonidine and Glutamate Receptor Antagonists on Thermal and Formalin-Induced Pain in Rats Anesth. Analg., March 1, 2001; 92(3): 725 - 732. [Abstract] [Full Text] [PDF]

				T. Nishiyama, L. Gyermek, C. Lee, S. Kawasaki-Yatsugi, and T. Yamaguchi The Systemically Administered Competitive AMPA Receptor Antagonist, YM872, has Analgesic Effects on Thermal or Formalin-Induced Pain in Rats Anesth. Analg., December 1, 1999; 89(6): 1534 - 1534. [Abstract] [Full Text] [PDF]