Abstract
Voltage-gated sodium channels are large transmembrane protein complexes responsible for the propagation and transmission of electrical impulses through nerve, muscle and endocrine cells and cell systems. Dysregulated expression and/or functional changes of ion channel isoforms are found in many associated pathological conditions. In such cases, modulation of voltage gated sodium channels (NaV channels) is a recognised approach in medicinal chemistry. Multiple small-molecule active compounds are used for a plethora of NaV channel-linked indications, for example epilepsy and CNS disorders, arrhythmia, stroke and pain states such as congenital analgesia/hyperalgesia and neuropathic pain. As existent NaV channel modulators suffer mainly from selectivity issues and thus exert significant side effects, novel and selective NaV channel modulators would be beneficial. Consequently, the increased research on voltage-gated sodium channels has led to a large number of novel compounds that exploit classic binding site selectivity with state-dependence or functional selectivity. Such compounds offer selective targeting and new possibilities for studying the physiology of NaV channels and pathophysiology of the associated ailment conditions. This review consolidates the recent literature on NaV 1.3, 1.7 and 1.8 channel isoform selective and/or state-dependent modulators. In particular, their structure-activity relationship is illustrated, especially in the context of selectivity on a particular isoform, and their applicability in the therapy of neuropathic pain is described.
Keywords: Isoform selective inhibitors, NaV 1.3, NaV 1.7, NaV 1.8, neuropathic pain, state-dependent inhibitors, therapy of pain, voltage-gated sodium channels.
Current Medicinal Chemistry
Title:Isoform Selective Voltage-Gated Sodium Channel Modulators and the Therapy of Pain
Volume: 21 Issue: 2
Author(s): Marko Jukic, Danijel Kikelj and Marko Anderluh
Affiliation:
Keywords: Isoform selective inhibitors, NaV 1.3, NaV 1.7, NaV 1.8, neuropathic pain, state-dependent inhibitors, therapy of pain, voltage-gated sodium channels.
Abstract: Voltage-gated sodium channels are large transmembrane protein complexes responsible for the propagation and transmission of electrical impulses through nerve, muscle and endocrine cells and cell systems. Dysregulated expression and/or functional changes of ion channel isoforms are found in many associated pathological conditions. In such cases, modulation of voltage gated sodium channels (NaV channels) is a recognised approach in medicinal chemistry. Multiple small-molecule active compounds are used for a plethora of NaV channel-linked indications, for example epilepsy and CNS disorders, arrhythmia, stroke and pain states such as congenital analgesia/hyperalgesia and neuropathic pain. As existent NaV channel modulators suffer mainly from selectivity issues and thus exert significant side effects, novel and selective NaV channel modulators would be beneficial. Consequently, the increased research on voltage-gated sodium channels has led to a large number of novel compounds that exploit classic binding site selectivity with state-dependence or functional selectivity. Such compounds offer selective targeting and new possibilities for studying the physiology of NaV channels and pathophysiology of the associated ailment conditions. This review consolidates the recent literature on NaV 1.3, 1.7 and 1.8 channel isoform selective and/or state-dependent modulators. In particular, their structure-activity relationship is illustrated, especially in the context of selectivity on a particular isoform, and their applicability in the therapy of neuropathic pain is described.
Export Options
About this article
Cite this article as:
Jukic Marko, Kikelj Danijel and Anderluh Marko, Isoform Selective Voltage-Gated Sodium Channel Modulators and the Therapy of Pain, Current Medicinal Chemistry 2014; 21 (2) . https://dx.doi.org/10.2174/09298673113206660257
DOI https://dx.doi.org/10.2174/09298673113206660257 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...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
-
Neuro-Inflammatory Mechanisms in Developmental Disorders Associated with Intellectual Disability and Autism Spectrum Disorder: A Neuro- Immune Perspective
CNS & Neurological Disorders - Drug Targets Recent Advances in the Hofmann Rearrangement and Its Application to Natural Product Synthesis
Current Organic Chemistry Clinical, Immunological and Therapeutic Aspects of Autoimmune Encephalitis
Recent Patents on CNS Drug Discovery (Discontinued) Substance P Regulation in Epilepsy
Current Neuropharmacology Interactions between Ketamine and Magnesium for the Treatment of Pain: Current State of the Art
CNS & Neurological Disorders - Drug Targets Autism - A Comprehensive Array of Prominent Signs and Symptoms
Current Pharmaceutical Design Non-canonical Molecular Targets for Novel Analgesics: Intracellular Calcium and HCN Channels
Current Neuropharmacology Etiology of Neuroinflammatory Pathologies in Neurodegenerative Diseases: A Treatise
Current Psychopharmacology Reprogrammed Metabolism of Cancer Cells as a Potential Therapeutic Target
Current Pharmaceutical Design Functional Chemical Groups that May Likely Become a Source for the Synthesis of Novel Central Nervous System (CNS) Acting Drugs
Central Nervous System Agents in Medicinal Chemistry Polymer-Based Drug Delivery Devices for Neurological Disorders
CNS & Neurological Disorders - Drug Targets Neurocognitive Functioning and Cannabis Use in Schizophrenia
Current Pharmaceutical Design Recent Progress in Syntheses and Biological Activities of Kainic Acid and its Derivatives
Current Organic Chemistry From Anreps Phenomenon to Myocardial Hypertrophy: Role of the Na+/H+ Exchanger
Current Cardiology Reviews Central Serotonin2C Receptor: From Physiology to Pathology
Current Topics in Medicinal Chemistry Increased Neuronal Injury in Clock Gene Per-1 Deficient-Mice after Cerebral Ischemia
Current Neurovascular Research Quality of Life of Children with Cerebral Palsy: A Cross-Sectional KIDSCREEN study in the Southern part of the Netherlands
CNS & Neurological Disorders - Drug Targets Pharmacological Inhibition of Voltage-gated Ca<sup>2+</sup> Channels for Chronic Pain Relief
Current Neuropharmacology Neuroprotective Effects of Exercise Treatments After Injury: The Dual Role of Neurotrophic Factors
Current Neuropharmacology Central Anti-Cholinergic Syndrome Induced by Single Therapeutic Dose of Atropine
Current Drug Safety