ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2010
The glycine transporter-1 inhibitor SSR103800 displays a selective and specific antipsychotic-like profile in normal and transgenic mice.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18 citing papers in PubMed, 45 citations in OpenAlex.
- GlyT1 (SLC6A9) inhibition in neurological and psychiatric disorders.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Combination of Haloperidol With UNC9994, β-arrestin-Biased Analog of Aripiprazole, Ameliorates Schizophrenia-Related Phenotypes Induced by NMDAR Deficit in Mice.The international journal of neuropsychopharmacology · 2024Article
- Pharmacological modulation of phosphodiesterase-7 as a novel strategy for neurodegenerative disorders.Inflammopharmacology · 2022Review
- The mGluR2 positive allosteric modulator, SAR218645, improves memory and attention deficits in translational models of cognitive symptoms associated with schizophrenia.Scientific reports · 2016Article
- Temporal and spatial transcriptional fingerprints by antipsychotic or propsychotic drugs in mouse brain.PloS one · 2015Article
- Relationship between glycine transporter 1 inhibition as measured with positron emission tomography and changes in cognitive performances in nonhuman primates.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2014Article
- Deletion of forebrain glycine transporter 1 enhances conditioned freezing to a reliable, but not an ambiguous, cue for threat in a conditioned freezing paradigm.Behavioural brain research · 2014Article
- The relationship between glycine transporter 1 occupancy and the effects of the glycine transporter 1 inhibitor RG1678 or ORG25935 on object retrieval performance in scopolamine impaired rhesus monkey.Psychopharmacology · 2014Article
- Glycine transporters as novel therapeutic targets in schizophrenia, alcohol dependence and pain.Nature reviews. Drug discovery · 2013Review
- NMDA Receptor Activity in Neuropsychiatric Disorders.Frontiers in psychiatry · 2013Article
- Effects of novel, high affinity glycine transport inhibitors on frontostriatal dopamine release in a rodent model of schizophrenia.European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology · 2012Article
- Emerging approaches for treatment of schizophrenia: modulation of glutamatergic signaling.Discovery medicine · 2012Review
- Targeting glutamate synapses in schizophrenia.Trends in molecular medicine · 2011Review
- Comparative pharmacology of antipsychotics possessing combined dopamine D2 and serotonin 5-HT1A receptor properties.Psychopharmacology · 2011Review
- TAAR1 activation modulates monoaminergic neurotransmission, preventing hyperdopaminergic and hypoglutamatergic activity.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- Discordant behavioral effects of psychotomimetic drugs in mice with altered NMDA receptor function.Psychopharmacology · 2011Article
- Validation and pharmacological characterisation of MK-801-induced locomotor hyperactivity in BALB/C mice as an assay for detection of novel antipsychotics.Psychopharmacology · 2010Article
- Potential role of amino acids in pathogenesis of schizophrenia.International journal of health sciencesReview
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Authors and funding
4 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Schizophrenia has been initially associated with dysfunction in dopamine neurotransmission. However, the observation that antagonists of the glutamate N-methyl-D-aspartate (NMDA) receptor produce schizophrenic-like symptoms in humans has led to the idea of a dysfunctioning of the glutamatergic system via its NMDA receptor. As a result, there is a growing interest in the development of pharmacological agents with potential antipsychotic properties that enhance the activity of the glutamatergic system via a modulation of the NMDA receptor. Among them are glycine transporter-1 (GlyT1) inhibitors such as SSR103800, which indirectly enhance NMDA receptor function by increasing the glycine (a co-agonist for the NMDA receptor) levels in the synapse. This study aimed at investigating the potential antipsychotic-like properties of SSR103800, with a particular focus on models of hyperactivity, involving either drug challenge (ie, amphetamine and MK-801) or transgenic mice (ie, NMDA Nr1(neo-/-) and DAT(-/-)). Results showed that SSR103800 (10-30 mg/kg p.o.) blocked hyperactivity induced by the non-competitive NMDA receptor antagonist, MK-801 and partially reversed spontaneous hyperactivity of NMDA Nr1(neo-/-) mice. In contrast, SSR103800 failed to affect hyperactivity induced by amphetamine or naturally observed in dopamine transporter (DAT(-/-)) knockout mice (10-30 mg/kg p.o.). Importantly, both classical (haloperidol) and atypical (olanzapine, clozapine and aripiprazole) antipsychotics were effective in all these models of hyperactivity. However, unlike these latter, SSR103800 did not produce catalepsy (retention on the bar test) up to 30 mg/kg p.o. Together these findings show that the GlyT1 inhibitor, SSR103800, produces antipsychotic-like effects, which differ from those observed with compounds primarily targeting the dopaminergic system, and has a reduced side-effect potential as compared with these latter drugs.
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