Voltage-Gated Sodium Channels: Structure, Function, Pharmacology, and Clinical Indications

被引：390

作者：

Ruiz, Manuel de Lera ^{[1
]}

Kraus, Richard L. ^{[1
]}

机构：

[1] Merck Res Labs, West Point, PA 19486 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2015年 / 58卷 / 18期

关键词：

GAIN-OF-FUNCTION; MU-CONOTOXIN-KIIIA; ION-CHANNEL; SAXITOXIN RECEPTOR; FUNCTION MUTATIONS; ACTION-POTENTIALS; CRYSTAL-STRUCTURE; SCORPION TOXINS; HUWENTOXIN-IV; NA+ CHANNELS;

D O I：

10.1021/jm501981g

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The tremendous therapeutic potential of voltage-gated sodium channels (Nays) has been the subject of many studies in the past and is of intense interest today. Na(v)1.7 channels in particular have received much attention recently because of strong genetic validation of their involvement in nociception. Here we summarize the current status of research in the Na-v field and present the most relevant recent developments with respect to the molecular structure, general physiology, and pharmacology of distinct Na-v channel subtypes. We discuss Na-v channel ligands such as small molecules, toxins isolated from animal venoms, and the recently identified Na(v)1.7-selective antibody. Furthermore, we review eight characterized ligand binding sites on the Na-v channel a subunit. Finally, we examine possible therapeutic applications of Na-v ligands and provide an update on current clinical studies.

引用

页码：7093 / 7118

页数：26

共 204 条

[1] The scorpion toxin Amm VIII induces pain hypersensitivity through gain-of-function of TTX-sensitive Na+ channels [J].