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

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...

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Vydané v:Journal of medicinal chemistry Ročník 58; číslo 18; s. 7093 - 7118
Hlavní autori: de Lera Ruiz, Manuel, Kraus, Richard L
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: United States American Chemical Society 24.09.2015
Predmet:
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
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Popis
Shrnutí: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.
Bibliografia:ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-3
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ObjectType-Review-1
ISSN:0022-2623
1520-4804
DOI:10.1021/jm501981g