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
-
Regulation of miRNA Processing and miRNA Mediated Gene Repression in Cancer
MicroRNA Cellular and Network Mechanisms Underlying Memory Impairment Induced by Amyloid β Protein
Protein & Peptide Letters Single Amino Acid Repeats Connect Viruses to Neurodegeneration
Current Drug Discovery Technologies Targeting α7 Nicotinic Acetylcholine Receptors in the Treatment of Schizophrenia
Current Pharmaceutical Design An Appraisal of Current Pharmacological Perspectives of Sesamol: A Review
Mini-Reviews in Medicinal Chemistry Induction of Serine Racemase Expression and D-Serine Release from Microglia by Secreted Amyloid Precursor Protein (sAPP)
Current Alzheimer Research Dissecting the Mechanisms of Thrombogenesis and Atherosclerosis for Neurodegenerative Disorders
Current Neurovascular Research Metal Complexes, their Cellular Targets and Potential for Cancer Therapy
Current Pharmaceutical Design Editorial [Hot topic: Adenosine Receptor Ligands: Where Are We, and Where Are We Going? (Guest Editors: Tiziano Tuccinardi and Adriano Martinelli)]
Current Topics in Medicinal Chemistry Group I Metabotropic Receptor Neuroprotection Requires Akt and Its Substrates that Govern FOXO3a, Bim, and β-Catenin During Oxidative Stress
Current Neurovascular Research Pharmacological Properties and Therapeutic Potential of Naringenin: A Citrus Flavonoid of Pharmaceutical Promise
Current Pharmaceutical Design Lafora Progressive Myoclonus Epilepsy: Recent Insights into Cell Degeneration
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Three-dimensional Modelling of the Voltage-gated Sodium Ion Channel from Anopheles gambiae Reveals Spatial Clustering of Evolutionarily Conserved Acidic Residues at the Extracellular Sites
Current Neuropharmacology Editorial (Thematic Issue: Mitochondrial Biogenesis: Pharmacological Approaches)
Current Pharmaceutical Design Immune-Glutamatergic Dysfunction as a Central Mechanism of the Autism Spectrum Disorders
Current Medicinal Chemistry One Pot Synthesis, Characterization, DFT Studies and AIM Analyses of Ethyl-1-aryl-1H-tetrazole-5-carboxylate
Letters in Organic Chemistry Possible Role of NUCB2/nesfatin-1 in Adipogenesis
Current Pharmaceutical Design HIV-1 Reactivation Induced by Apicidin Involves Histone Modification in Latently Infected Cells
Current HIV Research Central Serotonin2C Receptor: From Physiology to Pathology
Current Topics in Medicinal Chemistry Herbal Medicine for Anxiety, Depression and Insomnia
Current Neuropharmacology