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Current Topics in Pharmacology   Volumes    Volume 15  Issue 2
Problems with class 3 antiarrhythmic agents: Conclusions of the past - perspectives of the future
Péter Nánási Jr., Péter P. Nánási
Pages: 11 - 18
Number of pages: 8
Current Topics in Pharmacology
Volume 15  Issue 2

Copyright © 2011 Research Trends. All rights reserved

The majority of the currently used antiarrhythmic drugs carry serious proarrhythmic risk at the same time. Regarding class 3 agents, their torsadogenic action, which is associated with the reverse rate-dependent mode of action of these drugs, is the most serious side-effect. This mini-review provides a mass of evidence suggesting that the reverse rate-dependent nature of class 3 antiarrhythmic drug-effects is a common feature of all cardioactive agents in human cardiac tissues, consequently, development of selective blockers of the rapid delayed rectifier K+ current (IKr) without reverse rate-dependent properties has little chance to succeed. A more promising approach might be to combine prolongation of action potential duration with interventions suitable to minimize arrhythmogenesis at slow heart rates. This can likely be achieved by combining K+ channel blocking drugs with blockers of plateau inward currents, such as L-type Ca2+ current and window Na+ current. This view is supported by the results obtained by either combining two distinct molecules, or by applying single drugs having intrinsically combined modes of action.
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