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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Bibliographic Details
Published inJournal of medicinal chemistry Vol. 58; no. 18; pp. 7093 - 7118
Main Authors de Lera Ruiz, Manuel, Kraus, Richard L
Format Journal Article
LanguageEnglish
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
Online AccessGet full text
ISSN0022-2623
1520-4804
DOI10.1021/jm501981g

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Abstract 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.
AbstractList The tremendous therapeutic potential of voltage-gated sodium channels (Na(v)s) 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 α subunit. Finally, we examine possible therapeutic applications of Na(v) ligands and provide an update on current clinical studies.
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.
Author de Lera Ruiz, Manuel
Kraus, Richard L
AuthorAffiliation Merck Research Laboratories
AuthorAffiliation_xml – name: Merck Research Laboratories
Author_xml – sequence: 1
  givenname: Manuel
  surname: de Lera Ruiz
  fullname: de Lera Ruiz, Manuel
  email: manuel.ruiz@merck.com
– sequence: 2
  givenname: Richard L
  surname: Kraus
  fullname: Kraus, Richard L
BackLink https://www.ncbi.nlm.nih.gov/pubmed/25927480$$D View this record in MEDLINE/PubMed
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Snippet 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....
The tremendous therapeutic potential of voltage-gated sodium channels (Na(v)s) has been the subject of many studies in the past and is of intense interest...
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SubjectTerms 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
Title Voltage-Gated Sodium Channels: Structure, Function, Pharmacology, and Clinical Indications
URI http://dx.doi.org/10.1021/jm501981g
https://www.ncbi.nlm.nih.gov/pubmed/25927480
https://www.proquest.com/docview/1716937011
Volume 58
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