Abstract
The simple amino acid glycine is implicated in both inhibitory and excitatory neurotransmission in mammalian central nervous system, and it modulates excitatory neurotransmission through its role as a necessary co-agonist for glutamatergic N-methyl-D-aspartate (NMDA) receptors. Given the involvement of NMDA receptor-mediated neurotransmission in complex cerebral processes such as cognition, pharmacological manipulation of extracellular synaptic glycine biology is an active area of pharmaceutical research to develop novel treatments for neuropsychiatric disorders. A key component of cerebral glycine metabolism is the glycine transporter type 1 (GlyT1) and elevation of extracellular synaptic glycine concentration by blockade of GlyT1 has been hypothesized to potentiate NMDA receptor function in vivo and to represent a rational approach for the treatment of schizophrenia and cognitive disorders. The present article will review the wealth of scientific evidence supporting that hypothesis and the medicinal chemistry effort by many pharmaceutical companies and academic institutions to develop potent and selective GlyT1 inhibitors.
Current Topics in Medicinal Chemistry
Title: Recent Progress in the Discovery of Non-Sarcosine Based GlyT1 Inhibitors
Volume: 10 Issue: 2
Author(s): Scott E. Wolkenberg and Cyrille Sur
Affiliation:
Abstract: The simple amino acid glycine is implicated in both inhibitory and excitatory neurotransmission in mammalian central nervous system, and it modulates excitatory neurotransmission through its role as a necessary co-agonist for glutamatergic N-methyl-D-aspartate (NMDA) receptors. Given the involvement of NMDA receptor-mediated neurotransmission in complex cerebral processes such as cognition, pharmacological manipulation of extracellular synaptic glycine biology is an active area of pharmaceutical research to develop novel treatments for neuropsychiatric disorders. A key component of cerebral glycine metabolism is the glycine transporter type 1 (GlyT1) and elevation of extracellular synaptic glycine concentration by blockade of GlyT1 has been hypothesized to potentiate NMDA receptor function in vivo and to represent a rational approach for the treatment of schizophrenia and cognitive disorders. The present article will review the wealth of scientific evidence supporting that hypothesis and the medicinal chemistry effort by many pharmaceutical companies and academic institutions to develop potent and selective GlyT1 inhibitors.
Export Options
About this article
Cite this article as:
Wolkenberg E. Scott and Sur Cyrille, Recent Progress in the Discovery of Non-Sarcosine Based GlyT1 Inhibitors, Current Topics in Medicinal Chemistry 2010; 10 (2) . https://dx.doi.org/10.2174/156802610790410974
DOI https://dx.doi.org/10.2174/156802610790410974 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Medicinal Chemistry Advancement in Life-Threatening Diseases
The current issue will highlight concise reports that specify ground-breaking insights, including the novel discovery of drug targets and their action mechanism or drugs of novel classes. These are projected to encourage medicinal chemistry future efforts to address the most challenging medical needs. The current issue highlights further efforts to ...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
- Announcements
Related Articles
-
Angiotensin II: Role in Skeletal Muscle Atrophy
Current Protein & Peptide Science OX40:OX40L Axis: Emerging Targets for Immunotherapy of Human Disease
Current Immunology Reviews (Discontinued) Astrocytes and Inflammasome: A Possible Crosstalk in Neurological Diseases
Current Medicinal Chemistry Disruption of Calcium Homeostasis in the Pathogenesis of Alzheimers Disease and Other Conformational Diseases
Current Alzheimer Research Selective Estrogen Receptor Modulators (SERMs): Effects on Multiple Organ Systems
Current Medicinal Chemistry Discovery of Nesfatin-1 and Overview of Biological Actions and New Developments
Current Pharmaceutical Design Infectious Agents and Neurodegenerative Diseases: Exploring the Links
Current Topics in Medicinal Chemistry Cytotoxic and Anticancer Activities of Isatin and Its Derivatives: A Comprehensive Review from 2000-2008
Anti-Cancer Agents in Medicinal Chemistry Current Status and Future Prospective of Immunointervention in Multiple Sclerosis
Current Medicinal Chemistry Construction and Analysis of mRNA and lncRNA Regulatory Networks Reveal the Key Genes Associated with Prostate Cancer Related Fatigue During Localized Radiation Therapy
Current Bioinformatics Regulation of Neural Stem Cells in the Human SVZ by Trophic and Morphogenic Factors
Current Signal Transduction Therapy Adenoviral Vector-Mediated Gene Transfer for Human Gene Therapy
Current Gene Therapy Commendation of Diligence A Legend in Neuroscience (1948-2018) Dr. Stephen D. Skaper, Ph.D
CNS & Neurological Disorders - Drug Targets Commentary ( The Renin Angiotensin System in Alzheimers Disease - Do Updates Highlight a Clinical and Biological Dichotomy? )
Current Alzheimer Research In silico Screening for Identification of Novel Anti-malarial Inhibitors by Molecular Docking, Pharmacophore Modeling and Virtual Screening
Medicinal Chemistry The Hypocretins and their Role in Narcolepsy
CNS & Neurological Disorders - Drug Targets Pharmacological Inhibition of PKR in APPswePS1dE9 Mice Transiently Prevents Inflammation at 12 Months of Age but Increases Aβ42 Levels in the Late Stages of the Alzheimer’s Disease
Current Alzheimer Research Inflammation as the Common Biological Link Between Depression and Cardiovascular Diseases: Can Carnosine Exert a Protective Role?
Current Medicinal Chemistry Protein Misfolding in Conformational Disorders: Rescue of Folding Defects and Chemical Chaperoning
Mini-Reviews in Medicinal Chemistry A Review on Different Analytical Techniques for Determination of DNP Drugs and their Metabolites in Pharmaceutical Formulations
Current Pharmaceutical Analysis