Protective effects of the calmodulin antagonist bepridil on ischaemia induced in the rat myocardium.

The effects of a block of the slow calcium channel by bepridil and its antagonising effects on calmodulin were determined in the ischaemic rat myocardium. When isolated rat hearts were treated with a cardioplegic solution containing bepridil or verapamil there was a significant diminution in ischaemic damage in the myocardium. Bepridil was more effective than verapamil in protecting against this ischaemic damage. Bepridil effectively inhibited the activation of calmodulin dependent enzymes, such as calcium calmodulin dependent cyclic nucleotide phosphodiesterase and myosin light chain kinase. The inhibitory effect of verapamil on these enzymes was weaker than that of bepridil. Since bepridil protects the myocardium and minimises ischaemia induced damage these events might be related to a calmodulin antagonistic action as well as a calcium channel blocking action.