ArticleMolecular psychiatry2005
Inhibition of system A-mediated glycine transport in cortical synaptosomes by therapeutic concentrations of clozapine: implications for mechanisms of action.
Article in Molecular psychiatry, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00538070 (The Effects of Glycine Transport Inhibition on Brain Glycine Concentration), which is not on this map. Cited by 48 papers.
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.
The Effects of Glycine Transport Inhibition on Brain Glycine Concentration
Who cites it
48 citing papers in PubMed, 138 citations in OpenAlex.
- Randomised controlled trial of clozapine in resistant schizophrenia and schizoaffective disorder.Journal of psychopharmacology (Oxford, England) · 2025Trial
- Neurophysiological Effects of Bitopertin in Schizophrenia.Journal of clinical psychopharmacology · 2017Trial
- Reduction of Pavlovian Bias in Schizophrenia: Enhanced Effects in Clozapine-Administered Patients.PloS one · 2016Trial
- Feasibility, safety, and efficacy of the combination of D-serine and computerized cognitive retraining in schizophrenia: an international collaborative pilot study.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2013Trial
- Oral glycine administration increases brain glycine/creatine ratios in men: a proton magnetic resonance spectroscopy study.Psychiatry research · 2009Trial
- 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
- Dysfunction of the NMDA Receptor in the Pathophysiology of Schizophrenia and/or the Pathomechanisms of Treatment-Resistant Schizophrenia.Biomolecules · 2024Review
- Multiple serum anti-glutamate receptor antibody levels in clozapine-treated/naïve patients with treatment-resistant schizophrenia.BMC psychiatry · 2024Article
- Article
- Glycine and clozapine: potential relevance for the treatment of Parkinson's disease.Neurodegenerative disease management · 2024Article
- Mismatch Negativity (MMN) as a Pharmacodynamic/Response Biomarker for NMDA Receptor and Excitatory/Inhibitory Imbalance-Targeted Treatments in Schizophrenia.Advances in neurobiology · 2024Review
- Article
- Changes in Brain Glutamate on Switching to Clozapine in Treatment-Resistant Schizophrenia.Schizophrenia bulletin · 2021Article
- Examining the safety, efficacy, and patient acceptability of inhaled loxapine for the acute treatment of agitation associated with schizophrenia or bipolar I disorder in adults.Neuropsychiatric disease and treatment · 2019Review
- Eradicating Suicide at Its Roots: Preclinical Bases and Clinical Evidence of the Efficacy of Ketamine in the Treatment of Suicidal Behaviors.International journal of molecular sciences · 2018Review
- Schizophrenia: synthetic strategies and recent advances in drug design.MedChemComm · 2018Review
- Functional dysconnectivity of the limbic loop of frontostriatal circuits in first-episode, treatment-naive schizophrenia.Human brain mapping · 2018Article
- Review
- Presynaptic Dopamine Capacity in Patients with Treatment-Resistant Schizophrenia Taking Clozapine: An [Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2017Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Clozapine is an atypical antipsychotic with particular efficacy in schizophrenia, possibly related to potentiation of brain N-methyl-D-aspartate receptor (NMDAR) -mediated neurotransmission. NMDARs are regulated in vivo by glycine, which is regulated in turn by glycine transporters. The present study investigates transport processes regulating glycine uptake into rat brain synaptosomes, along with effects of clozapine on synaptosomal glycine transport. Amino-acid uptake of amino acids was assessed in rat brain P2 synaptosomal preparations using a radiotransport assay. Synaptosomal glycine transport was inhibited by a series of amino acids and by the selective System A antagonist MeAIB (2-methyl-aminoisobutyric acid). Clozapine inhibited transport of both glycine and MeAIB, but not other amino acids, at concentrations associated with preferential clinical response (0.5-1 microg/ml). By contrast, other antipsychotics studied were ineffective. The novel glycine transport inhibitor N[3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)propyl]sarcosine (NFPS) produced biphasic inhibition of [(3)H]glycine transport, with IC(50) values of approximately 25 nM and 25 microM, respectively. NFPS inhibition of [(3)H]MeAIB was monophasic with a single IC(50) value of 31 microM. Clozapine significantly inhibited [(3)H]glycine binding even in the presence of 100 nM NFPS. In conclusion, this study suggests first that System A transporters, or a subset thereof, may play a critical role in regulation of synaptic glycine levels and by extension of NMDA receptor regulation, and second that System A antagonism may contribute to the differential clinical efficacy of clozapine compared with other typical or atypical antipsychotics.
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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.