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Analgesic effect of GT-0198, a structurally novel glycine transporter 2 inhibitor, in a mouse model of neuropathic pain.

Abstract
This study was conducted to identify the characteristic pharmacological features of GT-0198 that is phenoxymethylbenzamide derivatives. GT-0198 inhibited the function of glycine transporter 2 (GlyT2) in human GlyT2-expressing HEK293 cells and did not bind various major transporters or receptors of neurotransmitters in a competitive manner. Thus, GT-0198 is considered to be a comparatively selective GlyT2 inhibitor. Intravenous, oral, and intrathecal injections of GT-0198 decreased the pain-related response in a model of neuropathic pain with partial sciatic nerve ligation. This result suggests that GT-0198 has an analgesic effect. The analgesic effect of GT-0198 was abolished by the intrathecal injection of strychnine, a glycine receptor antagonist. Therefore, GT-0198 is considered to exhibit its analgesic effect via the activation of a glycine receptor by glycine following presynaptic GlyT2 inhibition in the spinal cord. In summary, GT-0198 is a structurally novel GlyT2 inhibitor bearing a phenoxymethylbenzamide moiety with in vivo efficacy in behavioral models of neuropathic pain.
AuthorsYu Omori, Mayumi Nakajima, Kazumi Nishimura, Eiki Takahashi, Tadamasa Arai, Masato Akahira, Tomohiko Suzuki, Mie Kainoh
JournalJournal of pharmacological sciences (J Pharmacol Sci) Vol. 127 Issue 3 Pg. 377-81 (Mar 2015) ISSN: 1347-8648 [Electronic] Japan
PMID25837937 (Publication Type: Journal Article)
CopyrightCopyright © 2015 Toray Industries, Inc. Production and hosting by Elsevier B.V. All rights reserved.
Chemical References
  • Analgesics
  • Benzamides
  • GT-0198
  • Glycine Plasma Membrane Transport Proteins
  • Piperidines
  • Phenoxybenzamine
  • Strychnine
Topics
  • Analgesics
  • Animals
  • Benzamides (administration & dosage, antagonists & inhibitors, chemistry, pharmacology)
  • Disease Models, Animal
  • Glycine Plasma Membrane Transport Proteins (antagonists & inhibitors)
  • HEK293 Cells
  • Humans
  • Ligation
  • Male
  • Mice, Inbred ICR
  • Neuralgia (drug therapy)
  • Phenoxybenzamine
  • Piperidines (administration & dosage, antagonists & inhibitors, chemistry, pharmacology)
  • Sciatic Nerve
  • Spinal Cord
  • Strychnine (pharmacology)

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