Abstract
Gamma-amino butyric acid (GABA), the major inhibitory neurotransmitter in the mammalian central nervous system, plays a key role in the regulation of neuronal transmission throughout the brain, affecting numerous physiological and psychological processes. Changes in GABA levels provoke disbalance between excitatory and inhibitory signals, and are involved in the development of numerous neuropsychiatric disorders. GABA exerts its effects via ionotropic (GABAA) and metabotropic (GABAB) receptors. Both types of receptors are targeted by many clinically important drugs that affect GABAergic function and are widely used in the treatment of anxiety disorder, epilepsy, insomnia, spasticity, aggressive behaviour, and other pathophysiological conditions and diseases. Of particular importance are drugs that modulate GABAA receptor complex, such as benzodiazepines, barbiturates, neuroactive steroids, intravenous and inhalational anesthetics, and ethanol. Molecular interactions and subsequent pharmacological effects induced by drugs acting at GABAA receptors are extremely complex due to structural heterogeneity of GABAA receptors and existence of numerous allosterically interconnected binding sites and various chemically distinct ligands that are able to bound to them. There is a growing interest in the development and application of subtype-selective drugs that will achieve specific therapeutic benefits without undesirable side effects. The aim of this review is to briefly summarize the key pharmacological properties of GABA receptors, and to present selected novel findings with the potential to open new perspectives in the development of more effective therapeutic strategies.
Keywords: GABA, GABA receptor pharmacology, benzodiazepines, neurosteroids.
Current Pharmaceutical Design
Title:GABA Receptors: Pharmacological Potential and Pitfalls
Volume: 21 Issue: 34
Author(s): Maja Jazvinscak Jembrek and Josipa Vlainic
Affiliation:
Keywords: GABA, GABA receptor pharmacology, benzodiazepines, neurosteroids.
Abstract: Gamma-amino butyric acid (GABA), the major inhibitory neurotransmitter in the mammalian central nervous system, plays a key role in the regulation of neuronal transmission throughout the brain, affecting numerous physiological and psychological processes. Changes in GABA levels provoke disbalance between excitatory and inhibitory signals, and are involved in the development of numerous neuropsychiatric disorders. GABA exerts its effects via ionotropic (GABAA) and metabotropic (GABAB) receptors. Both types of receptors are targeted by many clinically important drugs that affect GABAergic function and are widely used in the treatment of anxiety disorder, epilepsy, insomnia, spasticity, aggressive behaviour, and other pathophysiological conditions and diseases. Of particular importance are drugs that modulate GABAA receptor complex, such as benzodiazepines, barbiturates, neuroactive steroids, intravenous and inhalational anesthetics, and ethanol. Molecular interactions and subsequent pharmacological effects induced by drugs acting at GABAA receptors are extremely complex due to structural heterogeneity of GABAA receptors and existence of numerous allosterically interconnected binding sites and various chemically distinct ligands that are able to bound to them. There is a growing interest in the development and application of subtype-selective drugs that will achieve specific therapeutic benefits without undesirable side effects. The aim of this review is to briefly summarize the key pharmacological properties of GABA receptors, and to present selected novel findings with the potential to open new perspectives in the development of more effective therapeutic strategies.
Export Options
About this article
Cite this article as:
Jembrek Jazvinscak Maja and Vlainic Josipa, GABA Receptors: Pharmacological Potential and Pitfalls, Current Pharmaceutical Design 2015; 21 (34) . https://dx.doi.org/10.2174/1381612821666150914121624
DOI https://dx.doi.org/10.2174/1381612821666150914121624 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
Advances in the Molecular Pathogenesis of Inflammatory Bowel Disease
This thematic issue will emphasize the recent breakthroughs in the mechanisms of Inflammatory bowel disease (IBD) pathogenesis and devotes some understanding of both Crohn’s and ulcerative colitis. It is expected to include studies about cellular and genetic aspects, which help to precipitate the disease, and the immune system-gut microbiome relations ...read more
Blood-based biomarkers in large-scale screening for neurodegenerative diseases
Disease biomarkers are necessary tools that can be employ in several clinical context of use (COU), ranging from the (early) diagnosis, prognosis, prediction, to monitor of disease state and/or drug efficacy. Regarding neurodegenerative diseases, in particular Alzheimer’s disease (AD), a battery of well-validated biomarkers are available, such as cerebrospinal fluid ...read more
Diabetes mellitus: advances in diagnosis and treatment driving by precision medicine
Diabetes mellitus (DM) is a chronic degenerative metabolic disease with ever increasing prevalence worldwide which is now an epidemic disease affecting 500 million people worldwide. Insufficient insulin secretion from pancreatic β cells unable to maintain blood glucose homeostasis is the main feature of this disease. Multifactorial and complex nature of ...read more
Food-derived bioactive peptides against chronic diseases
Chronic diseases, such as cardiovascular diseases and metabolic diseases, have become a great threat to the human health in recent decades due to the excessive food consumption and the prevalence of sedentary lifestyle. As a class of natural compounds, food-derived bioactive peptides have been demonstrated to possess great potential for ...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
-
The Impact of Altered HCN1 Expression on Brain Function and Its Relationship
with Epileptogenesis
Current Neuropharmacology Probiotics/Prebiotics in Viral Respiratory Infections: Implication for Emerging Pathogens
Recent Patents on Biotechnology A Randomized, Double-Blind, Placebo-Controlled Pilot Trial of Safety and Tolerability of Two Doses of Divalproex Sodium in Outpatients with Probable Alzheimers Disease
Current Alzheimer Research An Update of the Classical and Novel Methods Used for Measuring Fast Neurotransmitters During Normal and Brain Altered Function
Current Neuropharmacology Editorial
Current Pediatric Reviews Tackling the Elusive Challenges Relevant to Conquering the 100-Plus Year Old Problem of Alzheimer’s Disease
Current Alzheimer Research The Role of CYPs and Transporters in the Biotransformation and Transport of the Anti-hepatitis C Antiviral Agents Asunaprevir, Daclatasvir, and Beclabuvir: Impact of Liver Disease, Race and Drug-drug Interactions on Safety and Efficacy
Current Drug Metabolism A Study of Applications of Machine Learning Based Classification Methods for Virtual Screening of Lead Molecules
Combinatorial Chemistry & High Throughput Screening On Various Metrics Used for Validation of Predictive QSAR Models with Applications in Virtual Screening and Focused Library Design
Combinatorial Chemistry & High Throughput Screening Pharmacotherapeutic Potential of Garlic in Age-Related Neurological Disorders
CNS & Neurological Disorders - Drug Targets Neurodevelopment in Schizophrenia: The Role of the Wnt Pathways
Current Neuropharmacology Examining the Causes of Maternal Mortality in Pregnant Women Since the Beginning of the COVID-19 Pandemic in Hamadan Province, Western Iran: A Research Article
Coronaviruses Phenolic Acids Exert Anticholinesterase and Cognition-Improving Effects
Current Alzheimer Research Editorial [Hot Topic: Anticonvulsant Agents (Guest Editor: Barbara Malawska)]
Current Topics in Medicinal Chemistry The Blood-brain Barrier and the Outer Blood-retina Barrier
Medicinal Chemistry Reviews - Online (Discontinued) HIV-1 Tat-Induced Changes in Synaptically-Driven Network Activity Adapt During Prolonged Exposure
Current HIV Research Editorial [Hot Topic: Regulation of Glutamate Synthesis Via Inhibition of Glutamate Carboxypeptidase II (GCPII): An Effective Method to Treat Central and Peripheral Nervous System Disorders (Guest Editors: Guido Cavaletti and Barbara Slusher)]
Current Medicinal Chemistry Redox Regulation and the Autistic Spectrum: Role of Tryptophan Catabolites, Immuno-inflammation, Autoimmunity and the Amygdala
Current Neuropharmacology Convulsions with Gastroenteritis: Reflections on some Cases and Tentative Diagnostic Score
Current Pediatric Reviews A Computational Prediction of Conserved MicroRNA Targets of Ion Channels in Vertebrates
Current Bioinformatics