Nexopamil [LU 49938] is the (S)-enantiomer of a phenylalkylamine derivative and has calcium channel blocking and serotonin2 receptor antagonist activity. Nexopamil's significant antifibrillatory effect during both coronary artery occlusion and abrupt reperfusion is reliably tracked by T-wave alternans magnitude. Because the major component of the protection could be reproduced by blockade of the L-type calcium channel with diltiazem, nexopamil's antiarrhythmic action appears to be due mainly to blockade of this channel. Nexopamil's antiplatelet action through blockade of 5-HT2 receptors may confer additional protection against reperfusion arrhythmias. Nexopamil was discontinued in phase 2 for angina pectoris in European Union.