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主题介绍:“离子通道与神经药理学:从过去到未来”。

Introduction to the Theme "Ion Channels and Neuropharmacology: From the Past to the Future".

机构信息

Department of Neuroscience, Physiology and Pharmacology, University College London, London WC1E 6BT, United Kingdom; email:

Departments of Pharmacology and Medicine, University of California, San Diego, La Jolla, California 92093, USA.

出版信息

Annu Rev Pharmacol Toxicol. 2020 Jan 6;60:1-6. doi: 10.1146/annurev-pharmtox-082719-110050.

Abstract

"Ion Channels and Neuropharmacology: From the Past to the Future" is the main theme of articles in Volume 60 of the . Reviews in this volume discuss a wide spectrum of therapeutically relevant ion channels and GPCRs with a particular emphasis on structural studies that elucidate drug binding sites and mechanisms of action. The regulation of ion channels by second messengers, including Ca and cyclic AMP, and lipid mediators is also highly relevant to several of the ion channels discussed, including KCNQ channels, HCN channels, L-type Ca channels, and AMPA receptors, as well as the aquaporin channels. Molecular identification of exactly where drugs bind in the structure not only elucidates their mechanism of action but also aids future structure-based drug discovery efforts to focus on relevant pharmacophores. The ion channels discussed here are targets for multiple nervous system diseases, including epilepsy and neuropathic pain. This theme complements several previous themes, including "New Therapeutic Targets," "New Approaches for Studying Drug and Toxicant Action: Applications to Drug Discovery and Development," and "New Methods and Novel Therapeutic Approaches in Pharmacology and Toxicology."

摘要

“离子通道与神经药理学:从过去到未来”是第 60 卷中的文章的主题。本卷中的综述讨论了广泛的具有治疗相关性的离子通道和 G 蛋白偶联受体,特别强调了阐明药物结合位点和作用机制的结构研究。第二信使(包括 Ca 和环 AMP)和脂质介质对离子通道的调节也与讨论的几种离子通道高度相关,包括 KCNQ 通道、HCN 通道、L 型 Ca 通道和 AMPA 受体,以及水通道。药物在结构中结合的确切位置的分子鉴定不仅阐明了其作用机制,还有助于未来基于结构的药物发现工作集中于相关药效团。这里讨论的离子通道是多种神经系统疾病的靶点,包括癫痫和神经性疼痛。这个主题补充了几个之前的主题,包括“新的治疗靶点”、“研究药物和毒物作用的新方法:在药物发现和开发中的应用”以及“药理学和毒理学中的新方法和新治疗方法”。

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