Abstract
In the central nervous system, glutamate is essential for a proper synaptic communication in neuronal networks supporting critical behavioral activities such as learning and memory. Dysfunction of glutamatergic excitatory neurotransmission has been implicated in numerous neurological and pyschiatric disorders and a growing body of research suggests that potentiation of NMDA receptor function may represent a novel approach for the treatment of schizophrenia. An actively pursued strategy to potentiate NMDA receptor function is to increase synaptic levels of the neurotransmitter glycine by blocking the glycine transporter type 1 (GlyT1). Since glycine acts as a co-agonist at the NMDA receptor, this approach could enhance the effectiveness of normal NMDA receptor-mediated glutamatergic neurotransmission. Recent research on the physiology of this uptake system as well as on the development and preclinical testing of novel GlyT1 inhibitors have greatly enhanced our knowledge of the role of this transporter in the modulation of NMDA receptor activity and suggested that this approach may be feasible. Clinical studies with novel glycine reuptake inhibitors will provide critical information regarding the validity of this therapeutic concept for the treatment of schizophrenia and other disorders associated with NMDA receptor hypofunction.
Keywords: GlyT1 gene, 12 transmembrane domains, dentate gyrus, prepulse inhibition, GlyT1 inhibitors
Current Drug Targets
Title: Glycine Transporter 1 Inhibitors and Modulation of NMDA Receptor-Mediated Excitatory Neurotransmission
Volume: 8 Issue: 5
Author(s): Cyrille Sur and Gene G. Kinney
Affiliation:
Keywords: GlyT1 gene, 12 transmembrane domains, dentate gyrus, prepulse inhibition, GlyT1 inhibitors
Abstract: In the central nervous system, glutamate is essential for a proper synaptic communication in neuronal networks supporting critical behavioral activities such as learning and memory. Dysfunction of glutamatergic excitatory neurotransmission has been implicated in numerous neurological and pyschiatric disorders and a growing body of research suggests that potentiation of NMDA receptor function may represent a novel approach for the treatment of schizophrenia. An actively pursued strategy to potentiate NMDA receptor function is to increase synaptic levels of the neurotransmitter glycine by blocking the glycine transporter type 1 (GlyT1). Since glycine acts as a co-agonist at the NMDA receptor, this approach could enhance the effectiveness of normal NMDA receptor-mediated glutamatergic neurotransmission. Recent research on the physiology of this uptake system as well as on the development and preclinical testing of novel GlyT1 inhibitors have greatly enhanced our knowledge of the role of this transporter in the modulation of NMDA receptor activity and suggested that this approach may be feasible. Clinical studies with novel glycine reuptake inhibitors will provide critical information regarding the validity of this therapeutic concept for the treatment of schizophrenia and other disorders associated with NMDA receptor hypofunction.
Export Options
About this article
Cite this article as:
Sur Cyrille and Kinney G. Gene, Glycine Transporter 1 Inhibitors and Modulation of NMDA Receptor-Mediated Excitatory Neurotransmission, Current Drug Targets 2007; 8 (5) . https://dx.doi.org/10.2174/138945007780618535
DOI https://dx.doi.org/10.2174/138945007780618535 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
Call for Papers in Thematic Issues
New drug therapy for eye diseases
Eyesight is one of the most critical senses, accounting for over 80% of our perceptions. Our quality of life might be significantly affected by eye disease, including glaucoma, diabetic retinopathy, dry eye, etc. Although the development of microinvasive ocular surgery reduces surgical complications and improves overall outcomes, medication therapy is ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Purine-Scaffold Hsp90 Inhibitors
Current Topics in Medicinal Chemistry Autophagy and Cell Death in Caenorhabditis elegans
Current Pharmaceutical Design Oxidative and Inflammatory Events in Prion Diseases: Can They Be Therapeutic Targets?
Current Aging Science Caffeine; the Forgotten Potential for Parkinson's Disease
CNS & Neurological Disorders - Drug Targets Hydrolytic Activity of Amyloid-beta and its Inhibition with Short Peptides
Current Medicinal Chemistry - Central Nervous System Agents The Role of Neuronal Insulin/Insulin-Like Growth Factor-1 Signaling for the Pathogenesis of Alzheimer’s Disease: Possible Therapeutic Implications
CNS & Neurological Disorders - Drug Targets Mitochondrial Tolerance to Drugs and Toxic Agents in Ageing and Disease
Current Drug Targets From Bitopic Inhibitors to Multitarget Drugs for the Future Treatment of Alzheimer’s Disease
Current Medicinal Chemistry The Effects of Testosterone Supplementation on Cognitive Functioning in Older Men.
CNS & Neurological Disorders - Drug Targets Intracranial MR Dynamics in Clinically Diagnosed Alzheimers Disease: The Emerging Concept of “Pulse Wave Encephalopathy”
Current Alzheimer Research Elicitation of Immune Responsiveness Against Antigenic Challenge in Age- Related Diseases: Effects of Red Wine Polyphenols
Current Pharmaceutical Design A1 Receptors Ligands: Past, Present and Future Trends
Current Topics in Medicinal Chemistry Cross-Talk Between NO Synthase Isoforms in Neuro-Inflammation: Possible Implications in HIV-Associated Neurocognitive Disorders
Current Medicinal Chemistry Castration Resistant Prostate Cancer: From Emerging Molecular Pathways to Targeted Therapeutic Approaches
Clinical Cancer Drugs Kallikrein-Kinin System Mediated Inflammation in Alzheimers Disease In Vivo
Current Alzheimer Research Cognition and Neuropathology in Aging: Multidimensional Perspectives from the Rush Religious Orders Study and Rush Memory and Aging Project
Current Alzheimer Research Lifestyle Modifications in the Treatment of Hypertension
Current Hypertension Reviews Estrogen Receptor Neurobiology and its Potential for Translation into Broad Spectrum Therapeutics for CNS Disorders
Current Molecular Pharmacology Noninvasive Assessment of Cytokines in Occupational Respiratory Diseases
Recent Patents on Inflammation & Allergy Drug Discovery Neuroglial Roots of Neurodegenerative Diseases: Therapeutic Potential of Palmitoylethanolamide in Models of Alzheimer’s Disease
CNS & Neurological Disorders - Drug Targets