glycine transporters

Sarcosine (Methylglycine) is a competitive inhibitor of the type I glycine transporter (GlyT1) and an N-methyl-D-aspartate receptor (NMDAR) co-agonist.

LY2365109 hydrochloride is a potent and selective GlyT1 inhibitor, with an IC50 of 15.8 nM for glycine uptake in cells over-expressing [hGlyT1a].

Bitopertin (Paliflutine) (RG1678, RO-4917838) is a potent inhibitor of glycine transporter 1 (GlyT1), with Ki of 8.1 nM for human hGlyT1b and IC50 of 22-25 nM in Chinese hamster ovary cells.

Opiranserin (VVZ-149) hydrochloride is a dual antagonist of glycine transporter type 2 (GlyT2) and serotonin receptor 2A (5HT2A), with IC50s of 0.86 and 1.3 μM, respectively. It shows antagonistic activity on rP2X3 (IC50=0.87 μM). It is development as an injectable agent for the treatment of postoperative pain.

L-4FPG is a Glycine derivative, inhibits the neutral amino acid transporters ASCT1 and ASCT2.

Opiranserin is a development as an injectable agent for the treatment of postoperative pain. Opiranserin is a non-opioid and non-NSAID analgesic candidate and is a dual antagonist of glycine transporter type 2 (GlyT2) and serotonin receptor 2A (5HT2A) (IC50s: 0.86 and 1.3 μM, respectively). Opiranserin displays antagonistic activity on rP2X3 (IC50=0.87 μM).

Butyryl-L-carnitine is a butyrate ester of carnitine. It is an inhibitor of intestinal transporters, blocking carnitine uptake by the carnitine transporter and glycine transport by the amino acid transporter in human retinal pigment epithelial (HRPE) cells (IC50s = 1.5 μM and 4.6 mM, respectively).

Potent and selective inhibitor of the glial glycine transporter GlyT1b (IC50 = 6.9 nM). Displays negligible activity at GlyT-2, adrenoreceptors, dopamine, 5HT receptors and noradrenaline, dopamine, 5HT and GABA transporters (pIC50 in vivo. Chue et al (2013) Glycine reuptake inhibition as a new therapeutic approach in schizophrenia: focus on the glycine transporter 1 (GlyT1). Curr.Pharm.Des. 19 1311 PMID:23194655 |Brown et al (2001) Discovery and SAR of org 24598-a selective glycine uptake inhibitor. Bioorg.Med.Chem.Lett. 11 2007 PMID:11454468 |Williams et al (2003) Development of a scintillation proximity assay for analysis of Na+/Cl- -dependent neurotransmitter transporter activity. Anal. Biochem. 321 31 PMID:12963052

GT-0198 is a novel glycine transporter 2 inhibitor showed activity in a mouse model of neuropathic pain. 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. GT-0198 is considered to be a comparatively selective GlyT2 inhibitor. GT-0198 is a structurally novel GlyT2 inhibitor bearing a phenoxymethylbenzamide moiety with in vivo efficacy in behavioral models of neuropathic pain.