Trial reportBiological psychiatry2018
Dose-Related Target Occupancy and Effects on Circuitry, Behavior, and Neuroplasticity of the Glycine Transporter-1 Inhibitor PF-03463275 in Healthy and Schizophrenia Subjects.
Trial report in Biological psychiatry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 3 syntheses or guidelines pooled it, 53 citations in OpenAlex.
- Glutamatergic Modulation of Brain Function in Psychosis: A Systematic Review of Neuroimaging Studies.Biological psychiatry. Cognitive neuroscience and neuroimaging · 2025Pooled it
- Functional imaging studies of acute administration of classic psychedelics, ketamine, and MDMA: Methodological limitations and convergent results.Neuroscience and biobehavioral reviews · 2023Pooled it
- Association of Ketamine With Psychiatric Symptoms and Implications for Its Therapeutic Use and for Understanding Schizophrenia: A Systematic Review and Meta-analysis.JAMA network open · 2020Pooled it
- Randomized controlled trial of the glycine transporter 1 inhibitor PF-03463275 to enhance cognitive training and neuroplasticity in schizophrenia.Schizophrenia research · 2023Trial
- A robust and reproducible connectome fingerprint of ketamine is highly associated with the connectomic signature of antidepressants.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021Trial
- Novel drug treatments for schizophrenia.Nature reviews. Drug discovery · 2026Review
- Modulation of glycine transporters as a novel therapeutic strategy in neuropsychiatry.Psychopharmacology · 2026Review
- A brief visual evoked potential (VEP) modulation assessment of experience-dependent plasticity recorded via wireless dry-EEG headset in Phase 1 clinical units.Scientific reports · 2026Article
- Finding the Right Dose: NMDA Receptor-Modulating Treatments for Cognitive and Plasticity Deficits in Schizophrenia and the Role of Pharmacodynamic Target Engagement.Biological psychiatry · 2025Review
- Neurocognition and NMDAR co-agonists pathways in individuals with treatment resistant first-episode psychosis: a 3-year follow-up longitudinal study.Molecular psychiatry · 2024Article
- Ketamine and the neurobiology of depression: Toward next-generation rapid-acting antidepressant treatments.Proceedings of the National Academy of Sciences of the United States of America · 2023Review
- Development of the novel GlyT1 inhibitor, iclepertin (BI 425809), for the treatment of cognitive impairment associated with schizophrenia.European archives of psychiatry and clinical neuroscience · 2023Review
- Strategies for Treatment of Disease-Associated Dementia Beyond Alzheimer's Disease: An Update.Current neuropharmacology · 2023Review
- Sensory tetanisation to induce long-term-potentiation-like plasticity: A review and reassessment of the approach.The European journal of neuroscience · 2022Review
- Progress and Pitfalls in Developing Agents to Treat Neurocognitive Deficits Associated with Schizophrenia.CNS drugs · 2022Review
- A public-private collaboration model for clinical innovation.Clinical and translational science · 2022Review
- Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels.Pharmacological reviews · 2021Review
- Visual cortical plasticity and the risk for psychosis: An interim analysis of the North American Prodrome Longitudinal Study.Schizophrenia research · 2021Article
- Article
- Multimodal Neuroimaging Study of Visual Plasticity in Schizophrenia.Frontiers in psychiatry · 2021Article
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundGlycine transporter-1 (GlyT1) inhibitors may ameliorate cognitive impairments associated with schizophrenia. The dose-related occupancy and target engagement of the GlyT1 inhibitor PF-03463275 were studied to inform optimal dose selection for a clinical trial for cognitive impairments associated with schizophrenia.
methodsIn substudy 1, the effects of PF-03463275 (10, 20, and 40 mg twice a day) on occupancy of GlyT1 were tested using positron emission tomography and
resultsPF-03463275 at 10, 20, 40, and 60 mg twice a day produced ∼44%, 61%, 76%, and 83% GlyT1 occupancy, respectively, in SZs with higher ligand binding to GlyT1 in subcortical versus cortical regions. PF-03463275 did not attenuate any ketamine-induced effects but did improve working memory accuracy in healthy control subjects. PF-03463275 increased long-term potentiation only in SZs with peak effects at 40 mg twice a day (∼75% GlyT1 occupancy) and with a profile suggestive of an inverted U dose response. PF-03463275 was well-tolerated.
conclusionsThe dose-related GlyT1 occupancy of PF-03463275 is linear. While PF-03463275 did not show evidence of facilitating N-methyl-D-aspartate receptor function in the ketamine assay, it enhanced neuroplasticity in SZs. These findings provide support for a clinical trial to test the ability of PF-03463275 to enhance cognitive remediation toward addressing cognitive impairments associated with schizophrenia.
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Registered trials
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.