Abstract
Glycine acts as an inhibitory neurotransmitter at glycine receptor (GlyR)-enriched synapses and as an obligatory co-agonist at the N-methyl-D-aspartate (NMDA) receptor, where it facilitates neuronal excitation. Two high-affinity and substrate selective transporters, glycine transporter-1 and glycine transporter-2 (GlyT-1 and GlyT-2), regulate extracellular glycine concentrations within the CNS and as such, play critical roles in maintaining a balance between inhibitory and excitatory neurotransmission. GlyT-1 inhibition has been extensively examined as a potential means by which to treat several CNS disorders that include schizophrenia, depression, anxiety, obsessive compulsive disorder (OCD), and addiction. More recently, preclinical studies have emerged that indicate the approach may also promote neuroprotection, provide a pharmacotherapeutic strategy for autism spectrum disorders (ASDs), and treat symptomology associated with pain, Parkinson’s disease, and epilepsy. This review examines the pharmacological aspects of GlyT-1 inhibition and describes drug discovery and development efforts toward the identification of novel inhibitors.
Keywords: Glutamate, Glycine, Glycine Receptor, Glycine transporter, GlyT-1, GlyT-2, NMDA receptor, Sarcosine.
Current Topics in Medicinal Chemistry
Title:Inhibitors of Glycine Transporter-1: Potential Therapeutics for the Treatment of CNS Disorders
Volume: 16 Issue: 29
Author(s): Christopher L. Cioffi and Peter R. Guzzo
Affiliation:
Keywords: Glutamate, Glycine, Glycine Receptor, Glycine transporter, GlyT-1, GlyT-2, NMDA receptor, Sarcosine.
Abstract: Glycine acts as an inhibitory neurotransmitter at glycine receptor (GlyR)-enriched synapses and as an obligatory co-agonist at the N-methyl-D-aspartate (NMDA) receptor, where it facilitates neuronal excitation. Two high-affinity and substrate selective transporters, glycine transporter-1 and glycine transporter-2 (GlyT-1 and GlyT-2), regulate extracellular glycine concentrations within the CNS and as such, play critical roles in maintaining a balance between inhibitory and excitatory neurotransmission. GlyT-1 inhibition has been extensively examined as a potential means by which to treat several CNS disorders that include schizophrenia, depression, anxiety, obsessive compulsive disorder (OCD), and addiction. More recently, preclinical studies have emerged that indicate the approach may also promote neuroprotection, provide a pharmacotherapeutic strategy for autism spectrum disorders (ASDs), and treat symptomology associated with pain, Parkinson’s disease, and epilepsy. This review examines the pharmacological aspects of GlyT-1 inhibition and describes drug discovery and development efforts toward the identification of novel inhibitors.
Export Options
About this article
Cite this article as:
Cioffi L. Christopher and Guzzo R. Peter, Inhibitors of Glycine Transporter-1: Potential Therapeutics for the Treatment of CNS Disorders, Current Topics in Medicinal Chemistry 2016; 16 (29) . https://dx.doi.org/10.2174/1568026616666160405113340
DOI https://dx.doi.org/10.2174/1568026616666160405113340 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...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
-
Neurochemical Imbalance in Epilepsy from Animal Model to Human
Current Psychopharmacology Role for GABA and Glu Plasma Membrane Transporters in the Interplay of Inhibitory and Excitatory Neurotransmission
Current Topics in Medicinal Chemistry Genes, Blame and Loss of Control: is there a Place in Criminal Law for a ‘Genetic Defense’?
Recent Advances in DNA & Gene Sequences (Discontinued) A Retrospective, Multi-Center Cohort Study Evaluating the Severity- Related Effects of Cerebrolysin Treatment on Clinical Outcomes in Traumatic Brain Injury
CNS & Neurological Disorders - Drug Targets Scorpion Extracts Inhibit Tumor Growth in Esophageal Cancer and Lung Adenocarcinoma
Current Signal Transduction Therapy Neuroprotective Methodologies of Co-Enzyme Q10 Mediated Brain Hemorrhagic Treatment: Clinical and Pre-Clinical Findings
CNS & Neurological Disorders - Drug Targets Design, Synthesis and Biological Evaluation of Benzimidazole-pyridine- Piperidine Hybrids as a New Class of Potent Antimicrobial Agents
Letters in Drug Design & Discovery Metabotropic Glutamate and Cannabinoid Receptor Crosstalk in Periaqueductal Grey Pain Processing
Current Neuropharmacology Supercritical Extraction of Heracleum persicum Plant and Mathematical Modeling
The Natural Products Journal Dry Age-Related Macular Degeneration: Recent Progress of Therapeutic approaches
Current Molecular Pharmacology Relationship Between the Chemokine Receptor CCR5 and Microglia in Neurological Disorders: Consequences of Targeting CCR5 on Neuroinflammation, Neuronal Death and Regeneration in a Model of Epilepsy
CNS & Neurological Disorders - Drug Targets Regulation of Medical Devices and their Clinical Trials Studies in the USA: An Update
Recent Innovations in Chemical Engineering Gender Medicine and Pharmacoeconomics: A Narrative Review of the International Literature of the Last 5 Years. A Revision of Evidences about the Relationship Between Gender and Economic Consumption in Health
Current Pharmaceutical Design Targeting Histone Deacetylases for the Treatment of Immune, Endocrine & Metabolic Disorders
Endocrine, Metabolic & Immune Disorders - Drug Targets Editorial [Hot Topic:Ion Channels as a Target for Drug Design (Executive Editor: Kwok-Keung Tai)]
Current Pharmaceutical Design Current Methods in the Automatic Tissue Segmentation of 3D Magnetic Resonance Brain Images
Current Medical Imaging Brivaracetam Prevents the Over-expression of Synaptic Vesicle Protein 2A and Rescues the Deficits of Hippocampal Long-term Potentiation In Vivo in Chronic Temporal Lobe Epilepsy Rats
Current Neurovascular Research Update on the Slow Delayed Rectifier Potassium Current (IKs): Role in Modulating Cardiac Function
Current Medicinal Chemistry Nutraceuticals, Nutritional Therapy, Phytonutrients, and Phytotherapy for Improvement of Human Health: A Perspective on Plant Biotechnology Application
Recent Patents on Biotechnology Mitochondrial Involvement in Psychiatric Illness in Adults
Current Psychiatry Reviews