Characterization of SSR103800, a selective inhibitor of the glycine transporter-1 in models predictive of therapeutic activity in schizophrenia

Pharmacol Biochem Behav. 2008 Nov;91(1):47-58. doi: 10.1016/j.pbb.2008.06.009. Epub 2008 Jun 24.


On native human, rat and mouse glycine transporter-1(GlyT1), SSR130800 behaves as a selective inhibitor with IC50 values of 1.9, 5.3 and 6.8 nM, respectively. It reversibly blocked glycine uptake in mouse brain cortical homogenates, increased extracellular levels of glycine in the rat prefrontal cortex, and potentiated NMDA-mediated excitatory postsynaptic currents in rat hippocampal slices. SSR103800 (30 mg/kg, p.o.) decreased MK-801- and PCP-induced locomotor hyperactivity in rodents. SSR103800 (1 and 10 mg/kg, p.o.) attenuated social recognition deficit in adult rats induced by neonatal injections of PCP (10 mg/kg, s.c., on post-natal day 7, 9 and 11). SSR103800 (3 mg/kg, p.o.) counteracted the deficit in short-term visual episodic-like memory induced by a low challenge dose of PCP (1 mg/kg, i.p.), in PCP-sensitized rats (10 mg/kg, i.p.). SSR103800 (30 mg/kg, i.p.) increased the prepulse inhibition of the startle reflex in DBA/1J mice. SSR103800 decreased defensive- and despair-related behaviors in the tonic immobility test in gerbils (10 and 30 mg/kg, p.o.) and in the forced-swimming procedure in rats (1 and 3 mg/kg, p.o.), respectively. These findings suggest that SSR103800 may have a therapeutic potential in the management of the core symptoms of schizophrenia and comorbid depression states.

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology
  • Antipsychotic Agents / pharmacology*
  • Discrimination, Psychological / drug effects
  • Dizocilpine Maleate / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Extracellular Space / drug effects
  • Extracellular Space / metabolism
  • Gerbillinae
  • Glycine / metabolism
  • Glycine Plasma Membrane Transport Proteins / antagonists & inhibitors*
  • Male
  • Mice
  • Motor Activity / drug effects
  • N-Methylaspartate / physiology
  • Phencyclidine / pharmacology
  • Recognition, Psychology / drug effects
  • Reflex, Startle / drug effects
  • Schizophrenia / drug therapy*
  • Stereoisomerism
  • Swimming / psychology


  • Antidepressive Agents
  • Antipsychotic Agents
  • Excitatory Amino Acid Antagonists
  • Glycine Plasma Membrane Transport Proteins
  • Slc6a9 protein, mouse
  • N-Methylaspartate
  • Dizocilpine Maleate
  • Phencyclidine
  • Glycine