The antiarrhythmic actions of bisaramil and penticainide result from mixed cardiac ion channel blockade.

•Bisaramil and penticainide were compared using in vitro and in vivo methods.•Both drugs block cardiac sodium and potassium channels.•Both drugs block electrical and ischemic arrhythmias.•Both drugs did not alter Index of Cardiovascular Electrophysiology Balance (iCEB).•Bisaramil and penticainide produce mixed cardiac ion channel blockade.