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

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. © 2015 toray industries,inc. production and hosting by elsevier b.v. on behalf of japanese pharmacological society. this is an open access article under the cc by-nc-nd license.