ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2014
Relationship between glycine transporter 1 inhibition as measured with positron emission tomography and changes in cognitive performances in nonhuman primates.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 27 citations in OpenAlex.
- Dose-Related Target Occupancy and Effects on Circuitry, Behavior, and Neuroplasticity of the Glycine Transporter-1 Inhibitor PF-03463275 in Healthy and Schizophrenia Subjects.Biological psychiatry · 2018Trial
- GlyT1 (SLC6A9) inhibition in neurological and psychiatric disorders.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Modulation of glycine transporters as a novel therapeutic strategy in neuropsychiatry.Psychopharmacology · 2026Review
- Pharmacokinetic profile of bitopertin, a selective GlyTNaunyn-Schmiedeberg's archives of pharmacology · 2023Article
- Impaired verbal memory function is related to anterior cingulate glutamate levels in schizophrenia: findings from the STRATA study.Schizophrenia (Heidelberg, Germany) · 2022Article
- Sex differences in the effects of a combined behavioral and pharmacological treatment strategy for cocaine relapse prevention in an animal model of cue exposure therapy.Behavioural brain research · 2020Article
- Further characterization of the GlyT-1 inhibitor Org25935: anti-alcohol, neurobehavioral, and gene expression effects.Journal of neural transmission (Vienna, Austria : 1996) · 2017Article
- GlyT-1 Inhibition Attenuates Attentional But Not Learning or Motivational Deficits of the Sp4 Hypomorphic Mouse Model Relevant to Psychiatric Disorders.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2015Article
- Relationship between in vivo receptor occupancy and efficacy of metabotropic glutamate receptor subtype 5 allosteric modulators with different in vitro binding profiles.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2015Article
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
Several lines of evidence suggest that schizophrenia is associated with deficits in glutamatergic transmission at the N-methyl-d-aspartate (NMDA) receptors. Glycine is a NMDA receptor co-agonist, and extracellular levels of glycine are regulated in the forebrain by the glycine type-1 transporters (GlyT-1). GlyT-1 inhibitors elevate extracellular glycine and thus potentiate NMDA transmission. This mechanism represents a promising new avenue for the treatment of schizophrenia. Here, the recently introduced positron emission tomography radiotracer [11C]GSK931145 was used to quantify the relationship between occupancy of GlyT-1 by a GlyT-1 inhibitor, Org 25935, and its impact on spatial working memory performances in rhesus monkeys. The effect of Org 25935 on working memory was assessed both in control conditions and during a state of relative NMDA hypofunction induced by ketamine administration, at a dose selected for each animal to reduce task performance by about 50%. Under control conditions, Org 25935 had no effect on working memory at GlyT-1 occupancies lower than 75% and significantly impaired working memory at occupancies higher than 75%. Under ketamine conditions, Org 25935 reversed the deficit in working memory induced by ketamine and did so optimally in the 40-70% GlyT-1 occupancy range. The results confirm the efficacy of this mechanism to correct working memory deficits associated with NMDA hypofunction. These data also suggest the existence of an inverted-U dose-response curve in the potential therapeutic effect of this class of compounds.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.