2-Chloro-3-(trifluoromethyl)-N-((S)-phenyl((S)-piperidin-2-yl)methyl)benzamide hydrochloride

SSR504734 is an orally active, selective and reversible inhibitor of human, rat, and mouse GlyT1 (IC50=18, 15, and 38 nM, respectively). SSR504734 shows anti-schizophrenia, anti-anxiety and anti-depression activities[1].

Signaling Pathways >> Membrane Transporter/Ion Channel >> GlyT

Research Areas >> Neurological Disease

Signaling Pathways >> Neuronal Signaling >> GlyT

hGlyT1:18 nM (IC50)

rGlyT1:15 nM (IC50)

SSR504734 (15 nM-86 μM; 10 min) inhibits glycine uptake in human SK-N-MC and rat C6 cells[1]. Cell Viability Assay[1] Cell Line: Human neuroblastoma (SK-N-MC) and rat astrocytoma (C6) cells Concentration: 15 nM-86 μM Incubation Time: 10 min Result: Showed IC50 values of 18 and 15 nM for human SK-N-MC and rat C6 cells, respectively.

SSR504734 (i.p. and p.o.; 1-100 mg/kg; once) treatment shows good oral bioavailability[1]. SSR504734 (i.p.; 30 mg/kg; once) induces a rapid and significant decrease of specific glycine uptake[1]. SSR504734 (i.p.; 10 mg/kg; once) increases extracellular levels of Glycine in the prefrontal cortex (PFC) of freely moving rats[1]. Animal Model: Male Sprague-Dawley rats[1] Dosage: 1-100 mg/kg Administration: Intraperitoneal injection and oral gavage.; 1-100 mg/kg; once Result: Showed ID50 values of 5.0 and 4.6 mg/kg for i.p. and p.o. treatments, respectively. Animal Model: Male Sprague-Dawley rats[1] Dosage: 30 mg/kg Administration: Intraperitoneal injection; 30 mg/kg; once Result: Maintained at about 80% inhibition from 1 to 7 h after administration. Animal Model: Male Sprague-Dawley rats[1] Dosage: 10 mg/kg Administration: Intraperitoneal injection; 10 mg/kg; once Result: Produced a rapid and sustained increase in PFC extracellular levels of glycine.

[1]. Ronan Depoortère, et al. Neurochemical, electrophysiological and pharmacological profiles of the selective inhibitor of the glycine transporter-1 SSR504734, a potential new type of antipsychotic. Neuropsychopharmacology. 2005 Nov;30(11):1963-85.