Abstract
Current antipsychotic medications are efficacious for the positive symptoms of schizophrenia. However, there remains a significant unmet need for alternate strategies that could result in improved tolerability and/or efficacy for negative and cognitive symptoms. A growing body of research suggests that NMDA mediated neuronal activity is involved in the etiology of schizophrenia. Glycine binds to a modulatory glycineB strychnine-insensitive binding site on the NR1 subunit of the NMDA receptor complex and acts necessary co-agonist for activation of the NMDA receptor. Thus, several approaches have emerged aimed towards modulating this glycine binding site. To date, the glycineB site agonists glycine and D-serine, the partial agonist, D-cycloserine and the glycine reuptake inhibitor, sarcosine, have been shown to provide relief to schizophrenic patients. These clinical findings, combined with a growing body of preclinical literature, support the notion that enhancing synaptic glycineB activity leads to an increase in the effectiveness of normal glutamatergic signaling at the NMDA receptor complex and provides efficacy for schizophrenic patients. Accordingly, the present review examines the role of glycineB site modulation as a therapeutic approach for the treatment of schizophrenia.
Keywords: hallucinations, cognitive dysfunction, dopaminergic transmission, glutamate, nmda-receptor antagonists
Current Neuropharmacology
Title: Glycine Site Modulators and Glycine Transporter-1 Inhibitors as Novel Therapeutic Targets for the Treatment of Schizophrenia
Volume: 3 Issue: 1
Author(s): Gene G. Kinney and Cyrille Sur
Affiliation:
Keywords: hallucinations, cognitive dysfunction, dopaminergic transmission, glutamate, nmda-receptor antagonists
Abstract: Current antipsychotic medications are efficacious for the positive symptoms of schizophrenia. However, there remains a significant unmet need for alternate strategies that could result in improved tolerability and/or efficacy for negative and cognitive symptoms. A growing body of research suggests that NMDA mediated neuronal activity is involved in the etiology of schizophrenia. Glycine binds to a modulatory glycineB strychnine-insensitive binding site on the NR1 subunit of the NMDA receptor complex and acts necessary co-agonist for activation of the NMDA receptor. Thus, several approaches have emerged aimed towards modulating this glycine binding site. To date, the glycineB site agonists glycine and D-serine, the partial agonist, D-cycloserine and the glycine reuptake inhibitor, sarcosine, have been shown to provide relief to schizophrenic patients. These clinical findings, combined with a growing body of preclinical literature, support the notion that enhancing synaptic glycineB activity leads to an increase in the effectiveness of normal glutamatergic signaling at the NMDA receptor complex and provides efficacy for schizophrenic patients. Accordingly, the present review examines the role of glycineB site modulation as a therapeutic approach for the treatment of schizophrenia.
Export Options
About this article
Cite this article as:
Kinney G. Gene and Sur Cyrille, Glycine Site Modulators and Glycine Transporter-1 Inhibitors as Novel Therapeutic Targets for the Treatment of Schizophrenia, Current Neuropharmacology 2005; 3 (1) . https://dx.doi.org/10.2174/1570159052773387
DOI https://dx.doi.org/10.2174/1570159052773387 |
Print ISSN 1570-159X |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6190 |
- 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
- Announcements
- Forthcoming Thematic Issues
Related Articles
-
Recent Discussions on Dopamine Supersensitivity Psychosis: Eight Points to Consider When Diagnosing Treatment-Resistant Schizophrenia
Current Neuropharmacology 3,4-Dihydroxyphenylacetaldehyde: A Potential Target for Neuroprotective Therapy in Parkinsons Disease
Current Drug Targets - CNS & Neurological Disorders Targeting Monoamine Oxidases with Multipotent Ligands: An Emerging Strategy in the Search of New Drugs Against Neurodegenerative Diseases
Current Medicinal Chemistry EDITORIAL (Thematic Issue: New Targets of Medical Treatment in Psychiatric Disorders)
Current Neuropharmacology Anti-Oxidants in Parkinson’s Disease Therapy: A Critical Point of View
Current Neuropharmacology The Use of Bifunctional NOP/Mu and NOP Receptor Selective Compounds for the Treatment of Pain, Drug Abuse, and Psychiatric Disorders
Current Pharmaceutical Design Recent Advances on Horizontal Lower Limb Rehabilitation Robot
Recent Patents on Mechanical Engineering Utilizing Delta Opioid Receptors and Peptides for Cytoprotection: Implications in Stroke and Other Neurological Disorders
CNS & Neurological Disorders - Drug Targets Adenosine A2A Receptor Antagonists and Parkinsons Disease: State of the Art and Future Directions
Current Pharmaceutical Design Restoration of the Striatal Dopamine Synthesis for Parkinsons Disease:Viral Vector-Mediated Enzyme Replacement Strategy
Current Gene Therapy Oxidative stress and Parkinson’s disease: New hopes in treatment with herbal antioxidants
Current Pharmaceutical Design Substance Abuse and Movement Disorders: Complex Interactions and Comorbidities
Current Drug Abuse Reviews Retraction Notice: Clinical Strategies for Preventing Postoperative Nausea and Vomiting After Middle Ear Surgery in Adult Patients
Current Drug Safety Different Generations of Type-B Monoamine Oxidase Inhibitors in Parkinson’s Disease: From Bench to Bedside
Current Neuropharmacology Update on the Adverse Effects of Clozapine: Focus on Myocarditis
Current Drug Safety Catatonia Due to a General Medical Condition (Organic Catatonia)
Current Psychiatry Reviews Pharmacology of L-type Calcium Channels: Novel Drugs for Old Targets?
Current Molecular Pharmacology Parkinson’s Disease: A Current Perspectives on Parkinson’s Disease and Key Bioactive Natural Compounds as Future Potential Drug Candidates
Current Drug Targets Prime Time for G-Protein-Coupled Receptor Heteromers as Therapeutic Targets for CNS disorders: The Dopamine D1-D3 Receptor Heteromer
CNS & Neurological Disorders - Drug Targets Therapeutic Strategies for Huntingtons Disease: From the Bench to the Clinic
Current Psychopharmacology