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

• Published in: Journal of medicinal chemistry Vol. 58; no. 18; pp. 7093 - 7118
• Main Authors: de Lera Ruiz, Manuel, Kraus, Richard L
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 24.09.2015
• Subjects: Animals; Biological Products - chemistry; Biological Products - pharmacology; Biological Products - therapeutic use; Cardiovascular Diseases - drug therapy; Cardiovascular Diseases - metabolism; Channelopathies - drug therapy; Channelopathies - genetics; Clinical Trials as Topic; Drug Industry; Epilepsy - drug therapy; Epilepsy - metabolism; Humans; Ion Channel Gating; Ligands; Mutation; Neoplasms - drug therapy; Neoplasms - metabolism; Neuromuscular Diseases - drug therapy; Neuromuscular Diseases - metabolism; Pain - drug therapy; Pain - metabolism; Protein Structure, Tertiary; Protein Subunits - chemistry; Protein Subunits - genetics; Protein Subunits - physiology; Respiratory Tract Diseases - drug therapy; Respiratory Tract Diseases - metabolism; Voltage-Gated Sodium Channel Blockers - chemistry; Voltage-Gated Sodium Channel Blockers - pharmacology; Voltage-Gated Sodium Channel Blockers - therapeutic use; Voltage-Gated Sodium Channels - chemistry; Voltage-Gated Sodium Channels - genetics; Voltage-Gated Sodium Channels - physiology
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm501981g

The tremendous therapeutic potential of voltage-gated sodium channels (Navs) has been the subject of many studies in the past and is of intense interest today. Nav1.7 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 Nav field and present the most relevant recent developments with respect to the molecular structure, general physiology, and pharmacology of distinct Nav channel subtypes. We discuss Nav channel ligands such as small molecules, toxins isolated from animal venoms, and the recently identified Nav1.7-selective antibody. Furthermore, we review eight characterized ligand binding sites on the Nav channel α subunit. Finally, we examine possible therapeutic applications of Nav ligands and provide an update on current clinical studies.