Abstract
There are many factors that influence drug block of voltage-gated Na+ channels (VGSC). Pharmacological agents vary in conformation, charge, and affinity. Different drugs have variable affinities to VGSC isoforms, and drug efficacy is affected by implicit tissue properties such as resting potential, action potential morphology, and action potential frequency. The presence of polymorphisms and mutations in the drug target can also influence drug outcomes. While VGSCs have been therapeutic targets in the management of cardiac arrhythmias, their potential has been largely overshadowed by toxic side effects. Nonetheless, many VGSC blockers exhibit inherent voltage- and use-dependent properties of channel block that have recently proven useful for the diagnosis and treatment of genetic arrhythmias that arise from defects in Na+ channels and can underlie idiopathic clinical syndromes. These defective channels suggest themselves as prime targets of disease and perhaps even mutation specific pharmacological interventions.
| Original language | English (US) |
|---|---|
| Title of host publication | Handbook of Experimental Pharmacology |
| Pages | 99-121 |
| Number of pages | 23 |
| Volume | 171 |
| DOIs | |
| State | Published - 2006 |
| Externally published | Yes |
Publication series
| Name | Handbook of Experimental Pharmacology |
|---|---|
| Volume | 171 |
| ISSN (Print) | 01712004 |
| ISSN (Electronic) | 18650325 |
Fingerprint
Keywords
- Antiarrhythmic
- Brugada Syndrome
- CAST
- Channelopathies
- Conduction disorders
- CYP
- Cytochrome enzymes
- Flecainide
- Isoform specificity
- Lidocaine
- Local anesthetic
- Long-QT Syndrome
- Molecular determinants
- Mutation
- Na 1.1
- Na+ channel blocker
- Na1.5
- Pharmacodynamics
- Pharmacokinetics
- Polymorphism
- Proarrhythmic
- Recovery from block
- SCN1A
- SCN5A
- Sicilian Gambit
- Singh-Vaughan Williams
- Structural determinants
- Tonic block
- TTX
- Use-dependent block
- VGSC
ASJC Scopus subject areas
- Pharmacology, Toxicology and Pharmaceutics(all)
- Biochemistry
Cite this
Cardiac Na+ channels as therapeutic targets for antiarrhythmic agents. / Glaaser, I. W.; Clancy, Colleen E.
Handbook of Experimental Pharmacology. Vol. 171 2006. p. 99-121 (Handbook of Experimental Pharmacology; Vol. 171).Research output: Chapter in Book/Report/Conference proceeding › Chapter
}
TY - CHAP
T1 - Cardiac Na+ channels as therapeutic targets for antiarrhythmic agents
AU - Glaaser, I. W.
AU - Clancy, Colleen E
PY - 2006
Y1 - 2006
N2 - There are many factors that influence drug block of voltage-gated Na+ channels (VGSC). Pharmacological agents vary in conformation, charge, and affinity. Different drugs have variable affinities to VGSC isoforms, and drug efficacy is affected by implicit tissue properties such as resting potential, action potential morphology, and action potential frequency. The presence of polymorphisms and mutations in the drug target can also influence drug outcomes. While VGSCs have been therapeutic targets in the management of cardiac arrhythmias, their potential has been largely overshadowed by toxic side effects. Nonetheless, many VGSC blockers exhibit inherent voltage- and use-dependent properties of channel block that have recently proven useful for the diagnosis and treatment of genetic arrhythmias that arise from defects in Na+ channels and can underlie idiopathic clinical syndromes. These defective channels suggest themselves as prime targets of disease and perhaps even mutation specific pharmacological interventions.
AB - There are many factors that influence drug block of voltage-gated Na+ channels (VGSC). Pharmacological agents vary in conformation, charge, and affinity. Different drugs have variable affinities to VGSC isoforms, and drug efficacy is affected by implicit tissue properties such as resting potential, action potential morphology, and action potential frequency. The presence of polymorphisms and mutations in the drug target can also influence drug outcomes. While VGSCs have been therapeutic targets in the management of cardiac arrhythmias, their potential has been largely overshadowed by toxic side effects. Nonetheless, many VGSC blockers exhibit inherent voltage- and use-dependent properties of channel block that have recently proven useful for the diagnosis and treatment of genetic arrhythmias that arise from defects in Na+ channels and can underlie idiopathic clinical syndromes. These defective channels suggest themselves as prime targets of disease and perhaps even mutation specific pharmacological interventions.
KW - Antiarrhythmic
KW - Brugada Syndrome
KW - CAST
KW - Channelopathies
KW - Conduction disorders
KW - CYP
KW - Cytochrome enzymes
KW - Flecainide
KW - Isoform specificity
KW - Lidocaine
KW - Local anesthetic
KW - Long-QT Syndrome
KW - Molecular determinants
KW - Mutation
KW - Na 1.1
KW - Na+ channel blocker
KW - Na1.5
KW - Pharmacodynamics
KW - Pharmacokinetics
KW - Polymorphism
KW - Proarrhythmic
KW - Recovery from block
KW - SCN1A
KW - SCN5A
KW - Sicilian Gambit
KW - Singh-Vaughan Williams
KW - Structural determinants
KW - Tonic block
KW - TTX
KW - Use-dependent block
KW - VGSC
UR - http://www.scopus.com/inward/record.url?scp=33645965907&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33645965907&partnerID=8YFLogxK
U2 - 10.1007/3-540-29715-4-4
DO - 10.1007/3-540-29715-4-4
M3 - Chapter
C2 - 16610342
AN - SCOPUS:33645965907
SN - 9783540249672
VL - 171
T3 - Handbook of Experimental Pharmacology
SP - 99
EP - 121
BT - Handbook of Experimental Pharmacology
ER -