Abstract
Background: The Kv7 (KCNQ) subfamily of voltage-gated potassium channels consists of 5 members (Kv7.1-5) each showing characteristic tissue distribution and physiological roles. Given their functional heterogeneity, Kv7 channels represent important pharmacological targets for the development of new drugs for neuronal, cardiovascular and metabolic diseases.
Objective: In the present manuscript, we focus on describing the pharmacological relevance and potential therapeutic applications of drugs acting on neuronally-expressed Kv7.2/3 channels, placing particular emphasis on the different chemotypes, and highlighting their pharmacodynamic and, whenever possible, pharmacokinetic peculiarities.
Methods: The present work is based on an in-depth search of the currently available scientific literature, and on our own experience and knowledge in the field of neuronal Kv7 channel pharmacology. Space limitations impeded to describe the full pharmacological potential of Kv7 channels; thus, we have chosen to focus on neuronal channels composed of Kv7.2 and Kv7.3 subunits, and to mainly concentrate on their involvement in epilepsy.
Results: An astonishing heterogeneity in the molecular scaffolds exploitable to develop Kv7.2/3 modulators is evident, with important structural/functional peculiarities of distinct compound classes.
Conclusion: In the present work we have attempted to show the current status and growing potential of the Kv7 pharmacology field. We anticipate a bright future for the field, and express our hopes that the efforts herein reviewed will result in an improved treatment of hyperexcitability (or any other) diseases.
Keywords: Ion channels, Kv7 channels, channelopathies, retigabine, gating modifier.
Current Medicinal Chemistry
Title:Pharmacological Targeting of Neuronal Kv7.2/3 Channels: A Focus on Chemotypes and Receptor Sites
Volume: 25 Issue: 23
Author(s): Francesco Miceli, Maria V. Soldovieri, Paolo Ambrosino, Laura Manocchio, Ilaria Mosca and Maurizio Taglialatela*
Affiliation:
- Department of Neuroscience, University of Naples “Federico II”, 80131 Naples,Italy
Keywords: Ion channels, Kv7 channels, channelopathies, retigabine, gating modifier.
Abstract: Background: The Kv7 (KCNQ) subfamily of voltage-gated potassium channels consists of 5 members (Kv7.1-5) each showing characteristic tissue distribution and physiological roles. Given their functional heterogeneity, Kv7 channels represent important pharmacological targets for the development of new drugs for neuronal, cardiovascular and metabolic diseases.
Objective: In the present manuscript, we focus on describing the pharmacological relevance and potential therapeutic applications of drugs acting on neuronally-expressed Kv7.2/3 channels, placing particular emphasis on the different chemotypes, and highlighting their pharmacodynamic and, whenever possible, pharmacokinetic peculiarities.
Methods: The present work is based on an in-depth search of the currently available scientific literature, and on our own experience and knowledge in the field of neuronal Kv7 channel pharmacology. Space limitations impeded to describe the full pharmacological potential of Kv7 channels; thus, we have chosen to focus on neuronal channels composed of Kv7.2 and Kv7.3 subunits, and to mainly concentrate on their involvement in epilepsy.
Results: An astonishing heterogeneity in the molecular scaffolds exploitable to develop Kv7.2/3 modulators is evident, with important structural/functional peculiarities of distinct compound classes.
Conclusion: In the present work we have attempted to show the current status and growing potential of the Kv7 pharmacology field. We anticipate a bright future for the field, and express our hopes that the efforts herein reviewed will result in an improved treatment of hyperexcitability (or any other) diseases.
Export Options
About this article
Cite this article as:
Miceli Francesco, Soldovieri V. Maria, Ambrosino Paolo, Manocchio Laura , Mosca Ilaria and Taglialatela Maurizio*, Pharmacological Targeting of Neuronal Kv7.2/3 Channels: A Focus on Chemotypes and Receptor Sites, Current Medicinal Chemistry 2018; 25 (23) . https://dx.doi.org/10.2174/0929867324666171012122852
DOI https://dx.doi.org/10.2174/0929867324666171012122852 |
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
-
Editorial: Antiepileptic Drugs in Neurosurgical Practic
Current Pharmaceutical Design Adverse Drug Reactions of Anti-Epileptic Drugs in Children with Epilepsy: A Cross-Sectional Study
Current Drug Safety Phosphodiesterase 7A: A New Therapeutic Target for Alleviating Chronic Inflammation?
Current Pharmaceutical Design Salidroside - Can it be a Multifunctional Drug?
Current Drug Metabolism Targeted Toxins for Glioblastoma Multiforme: Pre-Clinical Studies and Clinical Implementation
Anti-Cancer Agents in Medicinal Chemistry Using PET Studies of P-gp Function to Elucidate Mechanisms Underlying the Disposition of Drugs
Current Topics in Medicinal Chemistry Neurocognitive Functioning and Cannabis Use in Schizophrenia
Current Pharmaceutical Design Synthetic Cannabinoid Receptor Agonists and Antagonists: Implication in CNS Disorders
Recent Patents on CNS Drug Discovery (Discontinued) Levetiracetam might act as an efficacious drug to attenuate cognitive deficits of Alzheimer’s disease
Current Topics in Medicinal Chemistry Book Review: “Dendrites- Third Edition”
CNS & Neurological Disorders - Drug Targets Cognitive Improvement by Photic Stimulation in a Mouse Model of Alzheimer’s Disease
Current Alzheimer Research QSAR Modeling of Histamine H3R Antagonists/inverse Agonists as Future Drugs for Neurodegenerative Diseases
Current Neuropharmacology Brain-Delivery of Zinc-Ions as Potential Treatment for Neurological Diseases: Mini Review
Drug Delivery Letters Menthone Semicarbazides and Thiosemicarbazides as Anticonvulsant Agents
Medicinal Chemistry Optimization of the Enzymolysis Conditions for Scorpion Peptides and Evaluation of its Antitumor Activity
Current Signal Transduction Therapy Targeting PPAR Isoforms Following CNS Injury
Current Drug Targets Efficient Synthesis of 5-Arylmethyl-5-phenylimidazolidine-2,4-dione (or 5-Arylmethyl-5-phenyl-2-thioxoimidazolidin-4-one) from Chalcone Oxides Under Ultrasound Irradiation
Letters in Organic Chemistry The Role of Topiramate and Other Anticonvulsants in the Treatment of Alcohol Dependence: A Clinical Review
CNS & Neurological Disorders - Drug Targets Developing Pharmacotherapies for Cannabis and Cocaine Use Disorders
Current Neuropharmacology SkQ-1 Regulates Xanthine Oxidase Activity in the Settings of Epilepsic Seizures in Rats
Neuroscience and Biomedical Engineering (Discontinued)