ReviewCurrent topics in medicinal chemistry2013
Allosteric modulators for the treatment of schizophrenia: targeting glutamatergic networks.
Review in Current topics in medicinal chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis 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
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 85 citations in OpenAlex.
- Antidepressants for cognitive impairment in schizophrenia--a systematic review and meta-analysis.Schizophrenia research · 2014Pooled it
- Magnesium and Zinc in Schizophrenia.Biomedicines · 2025Review
- Review
- EAR-20 peptide, a novel NMDA receptor positive allosteric modulator.Frontiers in pharmacology · 2025Article
- Synthesis and Structure-Activity Relationships for Glutamate Transporter Allosteric Modulators.Journal of medicinal chemistry · 2024Article
- Oral ketamine may offer a solution to the ketamine conundrum.Psychopharmacology · 2023Review
- Characterization of a Novel M4 PAM PET Radioligand [11C]PF06885190 in Nonhuman Primates (NHP).Molecules (Basel, Switzerland) · 2023Article
- Effects of zinc sulfate on schizophrenia symptoms in patients undergoing atypical antipsychotic pharmacotherapy.Journal of family medicine and primary care · 2022Article
- Characterization in nonhuman primates of (R)-[European journal of nuclear medicine and molecular imaging · 2022Article
- Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels.Pharmacological reviews · 2021Review
- AMPA Receptor Surface Expression Is Regulated by S-Nitrosylation of Thorase and Transnitrosylation of NSF.Cell reports · 2020Article
- Toward a Glutamate Hypothesis of Frontotemporal Dementia.Frontiers in neuroscience · 2019Review
- Article
- Targeting the 5-HT2C Receptor in Biological Context and the Current State of 5-HT2C Receptor Ligand Development.Current topics in medicinal chemistry · 2019Review
- Multi-Target Approach for Drug Discovery against Schizophrenia.International journal of molecular sciences · 2018Review
- A Novel MACS chemical neuroscience · 2018Article
- Current Concepts and Treatments of Schizophrenia.Molecules (Basel, Switzerland) · 2018Review
- The Role of Cannabis within an Emerging Perspective on Schizophrenia.Medicines (Basel, Switzerland) · 2018Article
- A novel missense mutation in GRIN2A causes a nonepileptic neurodevelopmental disorder.Movement disorders : official journal of the Movement Disorder Society · 2018Article
- GLYX-13 Ameliorates Schizophrenia-Like Phenotype Induced by MK-801 in Mice: Role of Hippocampal NR2B and DISC1.Frontiers in molecular neuroscience · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Schizophrenia is a highly debilitating mental disorder which afflicts approximately 1% of the global population. Cognitive and negative deficits account for the lifelong disability associated with schizophrenia, whose symptoms are not effectively addressed by current treatments. New medicines are needed to treat these aspects of the disease. Neurodevelopmental, neuropathological, genetic, and behavioral pharmacological data indicate that schizophrenia stems from a dysfunction of glutamate synaptic transmission, particularly in frontal cortical networks. A number of novel pre- and postsynaptic mechanisms affecting glutamatergic synaptic transmission have emerged as viable targets for schizophrenia. While developing orthosteric glutamatergic agents for these targets has proven extremely difficult, targeting allosteric sites of these targets has emerged as a promising alternative. From a medicinal chemistry perspective, allosteric sites provide an opportunity of finding agents with better drug-like properties and greater target specificity. Furthermore, allosteric modulators are better suited to maintaining the highly precise temporal and spatial aspects of glutamatergic synaptic transmission. Herein, we review neuropathological and genomic/genetic evidence underscoring the importance of glutamate synaptic dysfunction in the etiology of schizophrenia and make a case for allosteric targets for therapeutic intervention. We review progress in identifying allosteric modulators of AMPA receptors, NMDA receptors, and metabotropic glutamate receptors, all with the aim of restoring physiological glutamatergic synaptic transmission. Challenges remain given the complexity of schizophrenia and the difficulty in studying cognition in animals and humans. Nonetheless, important compounds have emerged from these efforts and promising preclinical and variable clinical validation has been achieved.
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What OpenQuestion holds
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.