摘要
背景:Kv7(KCNQ)亚家族控钾离子通道由5个成员(Kv7.1-5)组成,每一个都具有其特有的组织分布和生理作用。鉴于其功能异质性,Kv7通道象征着一种重要的药理靶点,为开发新治疗神经元,心血管和代谢疾病的药物提供了基础。 目的:在本文中,我们着重描述药物作用于神经表达的Kv7.2/3通道的药物相关性和潜在的治疗应用,特别强调不同的化学类型,并强调其药效学,并且当有可能时,阐述其药代动力学特性。 方法:目前的工作是基于对现有的科学文献的深入搜索,以及我们自己在神经元KV7通道药理学领域的经验和知识。空间限制阻碍了KV7通道的充分药理学潜力,因此,我们选择专注于由Kv7.2和Kv7.3亚基组成的神经元通道,并主要集中于癫痫的参与。 结果:可明显地发现在开发KV7.2/3调节剂的分子支架具有重要的结构/功能特点的不同的化合物类中一个惊人的异质性,。 结论:在本工作中,我们试图展示KV7药理学领域的现状和增长潜力。期待一个具有发展潜力的未来领域,并对其表达我们的希望,本文的努力将促成一个针对过度兴奋(或任何其他)疾病的改进治疗方式。
关键词: 离子通道,Kv7通道,通道病,雷替加宾,门控修饰剂。
Current Medicinal Chemistry
Title:Pharmacological Targeting of Neuronal Kv7.2/3 Channels: A Focus on Chemotypes and Receptor Sites
Volume: 25 Issue: 23
关键词: 离子通道,Kv7通道,通道病,雷替加宾,门控修饰剂。
摘要: 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.
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Cite this article as:
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 |
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