Calcium-channel blockers have advanced the understanding of cardiac ion channel structure-function relationships, though this knowledge has not yet resulted in useful new antiarrhythmic drugs.
Despite significant advances in understanding the molecular mechanisms of calcium-channel blockers, this knowledge has not yet translated into the development of novel antiarrhythmic drugs.
Calcium-channels, blockers have an established role in the management of cardiac arrhythmias 1–5. They were identified empirically with the idea of achieving selective inhibition of voltage-gated calcium-channels and vasodilatation 6,7, but early laboratory studies of the hemodynamic and vascular effects of verapamil happened also to demonstrate efficacy against cardiac arrhythmias 1,8. The importance of the landmark paper by Vaughan Williams and Singh 9 is that it proposed a novel discrete mechanism for the drug control of arrhythmias that did not rely on the three mechanisms viz. local anaesthetic, anti-sympathetic or delay in repolarization already described 10. There were two major outcomes of this publication. First, the expanded and refined classification of antiarrhythmic drug actions heralded a period of development in antiarrhythmic drug strategies and encouraged critical thinking about the mechanisms of drug action. This contributed in turn to a more complete evaluation of antiarrhythmic drug therapy in general 11,12. Second, intravenous verapamil entered clinical practice leading to a complete change in the treatment of acute paroxysmal supraventricular tachycardia 13–15. The deployment of calcium-channel blockers in cardiac arrhythmias moved, of course, in parallel with increased use of this class of drug in coronary artery disease and hypertension 16,17. This growth was unencumbered until more recently when it has been clouded by controversy 17–21. This commentary will examine the cellular and molecular mechanisms of action and current applications of calcium-channel blockers in cardiac arrhythmias. We contend that there have been major advances in understanding the molecular mechanisms of action of these agents and this has substantially contributed to a greatly expanded knowledge of cardiac (and indeed non-cardiac) ion channel structure-function relationships 22. This explosion of knowledge however has not yet resulted in any useful new drugs 23. Despite this lack of progress …
Andrew A. Grace (Sat,) conducted a review in Cardiac arrhythmias. Calcium-channel blockers was evaluated. Calcium-channel blockers have advanced the understanding of cardiac ion channel structure-function relationships, though this knowledge has not yet resulted in useful new antiarrhythmic drugs.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: