Abstract
Voltage-gated sodium channels (VGSC) are responsible for the selective influx of sodium ions in excitable cells. A number of physiological phenomena such as muscle contraction, pain sensation, processing of neuronal information in the brain as well as neuronal regulation of peripheral tissues rely on the activity of these channels. On the other hand, abnormal activity of VGSC are implicated in several pathological processes (e.g., cardiac arrhythmias, epilepsy, and chronic pain) which in some cases (e.g., channelopathies such as myotonias) are linked to specific gene mutations. As a result, VGSC have never stopped attracting the attention of medicinal chemists and the quest for novel drugs to treat these ion channels-associated diseases continues. In this review, VGSC blocking agents reported in the last lustrum are scrutinised with the aim to give a medicinal chemistry perspective on the most interesting compounds classified on the basis of (i) potential therapeutic application, (ii) targeted VGSC isoforms, and (iii) chemical scaffolds. Finally, the clinical potential of selected drug candidates from each chemotype is evaluated by comparing their ligand efficiency metrics. Possible routes for improvement of these preclinical candidates are also discussed.
Keywords: Biophysics, Channelopathies, Chemotype, Drug discovery, Efficiency metrics, Electrophysiology, Lead compound, Scaffold.
Current Medicinal Chemistry
Title:Recent Trends in the Discovery of Small Molecule Blockers of Sodium Channels
Volume: 23 Issue: 22
Author(s): Roberta Gualdani, Maria Maddalena Cavalluzzi and Giovanni Lentini
Affiliation:
Keywords: Biophysics, Channelopathies, Chemotype, Drug discovery, Efficiency metrics, Electrophysiology, Lead compound, Scaffold.
Abstract: Voltage-gated sodium channels (VGSC) are responsible for the selective influx of sodium ions in excitable cells. A number of physiological phenomena such as muscle contraction, pain sensation, processing of neuronal information in the brain as well as neuronal regulation of peripheral tissues rely on the activity of these channels. On the other hand, abnormal activity of VGSC are implicated in several pathological processes (e.g., cardiac arrhythmias, epilepsy, and chronic pain) which in some cases (e.g., channelopathies such as myotonias) are linked to specific gene mutations. As a result, VGSC have never stopped attracting the attention of medicinal chemists and the quest for novel drugs to treat these ion channels-associated diseases continues. In this review, VGSC blocking agents reported in the last lustrum are scrutinised with the aim to give a medicinal chemistry perspective on the most interesting compounds classified on the basis of (i) potential therapeutic application, (ii) targeted VGSC isoforms, and (iii) chemical scaffolds. Finally, the clinical potential of selected drug candidates from each chemotype is evaluated by comparing their ligand efficiency metrics. Possible routes for improvement of these preclinical candidates are also discussed.
Export Options
About this article
Cite this article as:
Gualdani Roberta, Cavalluzzi Maddalena Maria and Lentini Giovanni, Recent Trends in the Discovery of Small Molecule Blockers of Sodium Channels, Current Medicinal Chemistry 2016; 23 (22) . https://dx.doi.org/10.2174/0929867323666160517121458
DOI https://dx.doi.org/10.2174/0929867323666160517121458 |
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
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
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread 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 Progress Towards the Development of DHQO Derivatives and Related Analogues with Inotropic Effects
Mini-Reviews in Medicinal Chemistry Spirooxindoles as Potential Pharmacophores
Mini-Reviews in Medicinal Chemistry Flavonoids and other Non-alkaloidal Constituents of Genus Erythrina: Phytochemical Review
Combinatorial Chemistry & High Throughput Screening Caring for Children with Medical Complexity: Definitions, Challenges and Solutions
Current Pediatric Reviews The Quest for Eldorado: Development of Radioligands for In Vivo Imaging of Nicotinic Acetylcholine Receptors in Human Brain
Current Pharmaceutical Design Pharmacological Treatment of Cannabis Dependence
Current Pharmaceutical Design New Avenue of Research: Antiepileptic Drug and Estradiol Neuroprotection in Epilepsy
Recent Patents on CNS Drug Discovery (Discontinued) The Role of T-Type Calcium Channels in Epilepsy and Pain
Current Pharmaceutical Design Possible Role of NUCB2/nesfatin-1 in Adipogenesis
Current Pharmaceutical Design Molecular Cytogenetics of Autism
Current Genomics History and Therapeutic Use of MAO-A Inhibitors: A Historical Perspective of MAO-A Inhibitors As Antidepressant Drug
Current Topics in Medicinal Chemistry Fragile X Mental Retardation Protein: Many Partners and Multiple Targets for a Promiscuous Function
Current Genomics Glycaemic Control: A Balancing Act or A Different Approach?
Current Diabetes Reviews Seizures and Antiepileptic Drugs: From Pathophysiology to Clinical Practice
Current Pharmaceutical Design Patent Selections:
Recent Patents on Inflammation & Allergy Drug Discovery An Update on Drug Interactions with the Herbal Medicine Ginkgo biloba
Current Drug Metabolism Central Serotonin2C Receptor: From Physiology to Pathology
Current Topics in Medicinal Chemistry Patent Annotations
Recent Patents on CNS Drug Discovery (Discontinued) Effect of Levetiracetam on Cognitive Function and Clonic Seizure Frequency in Children with Epilepsy
Current Molecular Medicine Therapeutic Role of Synaptic Vesicle Glycoprotein 2A (SV2A) in Modulating Epileptogenesis
CNS & Neurological Disorders - Drug Targets