Sodium Channel Molecular Conformations and Antiarrhythmic Drug Affinity
| Autor: | Dorothy A. Hanck, Gregory M. Lipkind, Michael F. Sheets, Harry A. Fozzard |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Models
Molecular Drug Quinidine Lidocaine Protein Conformation medicine.drug_class media_common.quotation_subject Mepivacaine Pharmacology Article Sodium Channels Structure-Activity Relationship Mexiletine medicine Animals Humans Flecainide media_common Molecular Structure Chemistry Local anesthetic Sodium Procainamide Mutagenesis Site-Directed Cardiology and Cardiovascular Medicine Anti-Arrhythmia Agents Ion Channel Gating Sodium Channel Blockers medicine.drug |
| Zdroj: | Trends in Cardiovascular Medicine. 20:16-21 |
| ISSN: | 1050-1738 |
| DOI: | 10.1016/j.tcm.2010.03.002 |
| Popis: | Class I cardiac antiarrhythmic drugs, for example, lidocaine, mexiletine, flecainide, quinidine, and procainamide, continue to play an important role in the therapy for cardiac arrhythmias because of the presence of use-dependent block. Lidocaine, as well as related drugs such as mepivacaine, bupivacaine, and cocaine, also belong to the class of medications referred to as local anesthetics. In this review, we will consider lidocaine as the prototypical antiarrhythmic drug because it continues to be widely used both as an antiarrhythmic drug (first used as an antiarrhythmic drug in 1950) as well as a local anesthetic agent. Both of these clinical uses depend upon block of sodium current (I(Na)), but it is the presence of use-dependent I(Na) block, that is, an increasing amount of block at faster heart rates, which enables a local anesthetic agent to be a useful antiarrhythmic drug. Although many early studies investigated the action of antiarrhythmic drugs on Na currents, the availability of site-directed mutant Na channels has enabled for major advances in understanding their mechanisms of action based upon molecular conformations of the Na channel. |
| Databáze: | OpenAIRE |
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