Pharmacology and expression analysis of glycine transporter GlyT1 with [3H]-(N-[3-(4′-fluorophenyl)-3-(4′phenylphenoxy)propyl])sarcosine

Synthesis and characterization of [125I]2-iodo N-[(S)-{(S)-1-methylpiperidin-2-yl}(phenyl)methyl]3-trifluoromethyl-benzamide as novel imaging probe for glycine transporter 1

“…This extraordinary potent inhibitory activity of ALX5407 correlates with the result of a previous report (IC 50 consistent with the results of other radioligands for GlyT1. 21,22 To characterize in vitro regional brain distributions of GlyT1. Therefore, our study attempted to perform in vivo studies in order to validate the effectiveness of radio-iodinated 5 as a SPECT imaging agent for GlyT1.…”

Glycine Transporter 1 Inhibitors and Modulation of NMDA Receptor-Mediated Excitatory Neurotransmission

“…GlyT2 has a restricted pattern of expression and is found in brain regions that receive an inhibitory glycinergic innervation such as the spinal cord, brainstem and cerebellum consistent with its preferential involvement in glycinergic neurotransmission [13,14,18,29]. In contrast GlyT1 has a widespread distribution in forebrain areas such as cortex, hippocampus and thalamus [13,14,16,18,30]. Whereas glycinergic synapses have been unequivocally identified in rat hippocampus [31], GlyT1 expression pattern in neocortex closely matches NMDA receptor distribution [13,14,16].…”

Transporters

“…This difference has been attributed to a single glycine residue in transmembrane domain 6 (serine residue in GlyT2) (Vandenberg et al, 2007). Inhibition of GLYT1 by the sarcosine derivatives NFPS, NPTS and Org24598 is non-competitive (Mallorga et al, 2003;Mezler et al, 2008). IC50 values for Org 24598 reported in the literature vary, most likely due to differences in assay conditions (Brown et al, 2001;Mallorga et al, 2003).…”