INTRODUCTION: There remains an unmet need for safe and effective antiarrhythmic 
drugs, especially for the treatment of atrial fibrillation. Vanoxerine is a drug 
that is free of adverse cardiac events in normal volunteers, yet is a potent 
blocker of the hERG (hK(v)11.1) cardiac potassium channel. Consequently,we 
hypothesized that vanoxerine might also be a potent blocker of cardiac calcium 
(Ca) and sodium (Na) currents, and would not affect transmural dispersion of 
repolarization.
METHODS: The whole cell patch clamp technique was used to measure currents from 
cloned ion channels overexpressed in stable cell lines and single ventricular 
myocytes. We measured intracellular action potentials from canine ventricular 
wedges and Purkinje fibers using sharp microelectrode technique.
RESULTS: We found that vanoxerine was a potent hK(v)11.1 blocker, and at 
submicromolar concentrations, it blocked Ca and Na currents in a strongly 
frequency-dependent manner. In the canine ventricular wedge preparation 
vanoxerine did not significantly affect transmural action potential waveforms, 
QT interval or transmural dispersion of repolarization.
CONCLUSIONS: Vanoxerine (1) is a potent blocker of cardiac hERG, Na and Ca 
channels; (2) block is strongly frequency-dependent especially for Na and Ca 
channels; and (3) transmural dispersion of ventricular repolarization is 
unaffected. The multichannel block and repolarization uniformity resemble the 
effects of amiodarone, the exemplar atrial fibrillation drug. Vanoxerine is a 
completely different chemical and has none of amiodarone's toxic effects. 
Vanoxerine has characteristics of a potentially effective and safe 
antiarrhythmic.