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The therapeutic potential of neuronal Kv7 (KCNQ) channel modulators: An update

机译：神经元Kv7（KCNQ）通道调节剂的治疗潜力：最新进展

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Background: Neuronal KCNQ channels (Kv7.2-5) represent attractive targets for the development of therapeutics for chronic and neuropathic pain, migraine, epilepsy and other neuronal hyperexcitability disorders, although there has been only modest progress in translating this potential into useful therapeutics. Objective: Compelling evidence of the importance of Kv7 channels as neuronal regulatory elements, readily amenable to pharmacological modulation, has sustained widespread interest in these channels as drug targets. This review will update readers on key aspects of the characterization of these important ion channel targets, and will discuss possible current barriers to their exploitation for CNS therapeutics. Methods: This article is based on a review of recent literature, with a focus on data pertaining to the roles of these channels in neurophysiology. In addition, I review some of the regulatory elements that influence the channels and how these may relate to channel pharmacology, and present a review of recent advances in neuronal Kv7 channel pharmacology. Conclusions: These channels continue to be valid and approachable targets for CNS therapeutics. However, we may need to understand more about the roles of neuronal Kv7 channels during the development of disease states, as well as to pay more attention to a detailed analysis of the molecular pharmacology of the different channel subfamily members and the modes of interaction of individual modulators, in order to successfully target these channels for therapeutic development.
机译：背景：神经元KCNQ通道（Kv7.2-5）代表了针对慢性和神经性疼痛，偏头痛，癫痫和其他神经元过度兴奋性疾病的治疗剂开发的诱人靶标，尽管在将这种潜力转化为有用的治疗剂方面仅取得了适度的进展。目的：令人信服的证据表明，Kv7通道作为易于调节药理作用的神经元调节元件的重要性，一直引起人们对这些通道作为药物靶标的广泛兴趣。这篇综述将向读者介绍这些重要离子通道靶标表征的关键方面，并讨论可能存在的阻碍其用于中枢神经系统疗法的障碍。方法：本文基于对近期文献的回顾，重点是与这些通道在神经生理学中的作用有关的数据。此外，我回顾了一些影响通道的调控因素，以及它们可能与通道药理学的关系，并综述了神经元Kv7通道药理学的最新进展。结论：这些渠道仍然是中枢神经系统治疗的有效和可接近的目标。但是，我们可能需要更多地了解神经元Kv7通道在疾病状态发展过程中的作用，并且需要更多地关注对不同通道亚家族成员的分子药理作用和个体相互作用方式的详细分析。调节剂，以成功靶向这些通道进行治疗性开发。

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