Abstract
The voltage-gated sodium channels (VGSCs) are a family of membrane proteins forming a pore, through which they selectively conduct sodium ions inward and outward cell’s plasma membranes in response to variations of membrane potentials, playing a fundamental role in controlling cellular excitability. Growing evidences suggest that abnormal VGSCs are involved in the pathophysiology of both acquired and inherited epilepsy. Approximately two dozen drugs are currently marketed for the treatment of epilepsy and most of them act as sodium channel blockers, preventing the return of the channels to the active state by stabilizing the inactive form. Despite the many drugs on the market, 30% of patients continue to experience seizures even in the presence of optimal doses of AEDs, while others continue to suffer from medication induced side effects. Thus, there is a great need to continue the search for new AEDs that are not only more effective, but also have a better side effects profile. For this reason, many efforts have been made in the recent years to identify new sodium channel blockers for the treatment of epilepsy. These studies have led to different classes of compounds, characterized by a great structural diversity. The aim of this review is to provide an introduction on the structure and function of the sodium channels, followed by a brief historical perspective on the sodium channel blockers in use as anticonvulsant drugs. Moreover, it will focus on the medicinal chemistry of the sodium channel blockers recently published (2008-2011) and the drug design/molecular modeling studies related to the receptor.
Keywords: Anticonvulsant drugs, benzodiazepinones, CoMFA, diarylimidazoles, epilepsy, sodium channel blockers
Current Topics in Medicinal Chemistry
Title:Sodium Channel Blockers as Therapeutic Target for Treating Epilepsy: Recent Updates
Volume: 12 Issue: 9
Author(s): Valentina Zuliani, Marco Fantini and Mirko Rivara
Affiliation:
Keywords: Anticonvulsant drugs, benzodiazepinones, CoMFA, diarylimidazoles, epilepsy, sodium channel blockers
Abstract: The voltage-gated sodium channels (VGSCs) are a family of membrane proteins forming a pore, through which they selectively conduct sodium ions inward and outward cell’s plasma membranes in response to variations of membrane potentials, playing a fundamental role in controlling cellular excitability. Growing evidences suggest that abnormal VGSCs are involved in the pathophysiology of both acquired and inherited epilepsy. Approximately two dozen drugs are currently marketed for the treatment of epilepsy and most of them act as sodium channel blockers, preventing the return of the channels to the active state by stabilizing the inactive form. Despite the many drugs on the market, 30% of patients continue to experience seizures even in the presence of optimal doses of AEDs, while others continue to suffer from medication induced side effects. Thus, there is a great need to continue the search for new AEDs that are not only more effective, but also have a better side effects profile. For this reason, many efforts have been made in the recent years to identify new sodium channel blockers for the treatment of epilepsy. These studies have led to different classes of compounds, characterized by a great structural diversity. The aim of this review is to provide an introduction on the structure and function of the sodium channels, followed by a brief historical perspective on the sodium channel blockers in use as anticonvulsant drugs. Moreover, it will focus on the medicinal chemistry of the sodium channel blockers recently published (2008-2011) and the drug design/molecular modeling studies related to the receptor.
Export Options
About this article
Cite this article as:
Zuliani Valentina, Fantini Marco and Rivara Mirko, Sodium Channel Blockers as Therapeutic Target for Treating Epilepsy: Recent Updates, Current Topics in Medicinal Chemistry 2012; 12 (9) . https://dx.doi.org/10.2174/156802612800229206
DOI https://dx.doi.org/10.2174/156802612800229206 |
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
-
Metabolic Reprogramming of Human Cells in Response to Oxidative Stress: Implications in the Pathophysiology and Therapy of Mitochondrial Diseases
Current Pharmaceutical Design Editorial (Thematic Issue: Linkage of Neurodegenerative Disorders with Other Health Issues – Volume I)
CNS & Neurological Disorders - Drug Targets On Chemical Structures with Potent Antiepileptic/Anticonvulsant Profile
Mini-Reviews in Medicinal Chemistry Nanoparticles as a Carrier System for Drug Delivery Across Blood Brain Barrier
Current Drug Metabolism On Some Physiological Aspects of Ethanol Repercussion on Neural and Cardiorenal Functions
Central Nervous System Agents in Medicinal Chemistry Neurotransmitter Regulation of Adult Neurogenesis: Putative Therapeutic Targets
CNS & Neurological Disorders - Drug Targets Towards the Molecular Foundations of Glutamatergic-targeted Antidepressants
Current Neuropharmacology Nanostructures for Drug Delivery to the Brain
Current Medicinal Chemistry Therapeutic Potential of Erythropoietin in Retinal and Optic Nerve Diseases
CNS & Neurological Disorders - Drug Targets Can FreeSurfer Compete with Manual Volumetric Measurements in Alzheimer’s Disease?
Current Alzheimer Research New Adamantane Derivatives with Sigma Affinity and Antiproliferative Activity
Medicinal Chemistry The Role of P-Glycoprotein in Psychiatric Disorders: A Reliable Guard of the Brain?
Central Nervous System Agents in Medicinal Chemistry Unexpected Effects of Acetylcholine Precursors on Pilocarpine Seizure- Induced Neuronal Death
Current Neuropharmacology Possible Physiopathological Roles of the Transglutaminase Activity in the Etiopathogenesis of Human Neurodegenerative Diseases
Recent Patents on CNS Drug Discovery (Discontinued) Gene Therapy for Neuroprotection and Neurorestoration (Part I)
Current Gene Therapy ABC Transporters in the Development of Multidrug Resistance in Cancer Therapy
Current Pharmaceutical Design Current κ Opioid Receptor Ligands and Discovery of a New Molecular Scaffold as a κ Opioid Receptor Antagonist Using Pharmacophore-Based Virtual Screening
Current Pharmaceutical Design Other Drugs Acting on Nervous System Associated with QT-Interval Prolongation
Current Drug Safety Review of the Phytochemistry and Biological Activity of Cissus incisa Leaves
Current Topics in Medicinal Chemistry Adaptive Behavior in Williams-Beuren Syndrome, Down Syndrome, and Autism Spectrum Disorder
Current Psychiatry Reviews