title: 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.
authors.affiliation: Toray Industries, Inc., Pharmaceutical Research Laboratories, 10-1, Tebiro 6-chome, Kamakura, Kanagawa 248-8555, Japan. Electronic address: Yu_Omori@nts.toray.co.jp.
authors.forename: Yu
authors.initials: Y
authors.lastname: Omori
authors.affiliation: Toray Industries, Inc., Pharmaceutical Research Laboratories, 10-1, Tebiro 6-chome, Kamakura, Kanagawa 248-8555, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Nakajima
authors.affiliation: Toray Industries, Inc., Pharmaceutical Research Laboratories, 10-1, Tebiro 6-chome, Kamakura, Kanagawa 248-8555, Japan.
authors.forename: Kazumi
authors.initials: K
authors.lastname: Nishimura
authors.affiliation: Toray Industries, Inc., Pharmaceutical Research Laboratories, 10-1, Tebiro 6-chome, Kamakura, Kanagawa 248-8555, Japan.
authors.forename: Eiki
authors.initials: E
authors.lastname: Takahashi
authors.affiliation: Toray Industries, Inc., Pharmaceutical Research Laboratories, 10-1, Tebiro 6-chome, Kamakura, Kanagawa 248-8555, Japan.
authors.forename: Tadamasa
authors.initials: T
authors.lastname: Arai
authors.affiliation: Toray Industries, Inc., Pharmaceutical Research Laboratories, 10-1, Tebiro 6-chome, Kamakura, Kanagawa 248-8555, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Akahira
authors.affiliation: Toray Industries, Inc., Pharmaceutical Research Laboratories, 10-1, Tebiro 6-chome, Kamakura, Kanagawa 248-8555, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Toray Industries, Inc., Pharmaceutical Research Laboratories, 10-1, Tebiro 6-chome, Kamakura, Kanagawa 248-8555, Japan.
authors.forename: Mie
authors.initials: M
authors.lastname: Kainoh
mesh_terms: D000700:Analgesics; D000818:Animals; D001549:Benzamides / Q000008:administration & dosage* / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000494:pharmacology*; D004195:Disease Models, Animal; D050487:Glycine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors*; D057809:HEK293 Cells; D006801:Humans; D008026:Ligation; D008297:Male; D008813:Mice, Inbred ICR; D009437:Neuralgia / Q000188:drug therapy*; D010643:Phenoxybenzamine; D010880:Piperidines / Q000008:administration & dosage* / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000494:pharmacology*; D012584:Sciatic Nerve; D013116:Spinal Cord; D013331:Strychnine / Q000494:pharmacology
chemical_list: D000700:Analgesics; D001549:Benzamides; C000606303:GT-0198; D050487:Glycine Plasma Membrane Transport Proteins; D010880:Piperidines; D010643:Phenoxybenzamine; D013331:Strychnine
keywords: Glycine; Glycine transporter; Neuropathic pain; Partial sciatic nerve ligation