ANTIARRHYTHMIC AGENT AMIODARONE POSSESSES CALCIUM-CHANNEL BLOCKER PROPERTIES

Amiodarone possesses multiple pharmacologic properties, including peri pheral and coronary vasodilatation, negative inotropy, and negative ch ronotropic and dromotropic effects. These properties are shared by the group of drugs termed calcium channel blockers. We examined the inter action of amiodarone with receptors for the 1,4-dihydropyridine (DHP) calcium blockers in rat and rabbit myocardial membrane particulates. A miodarone displaced specifically bound [H-3]nitrendipine in both rat a nd rabbit preparations in a competitive, concentration-dependent manne r at a single class of binding sites (K-i similar to 0.27 mu M). Calci um channel blocking activity was determined pharmacologically in a tis sue bath with electrically stimulated rabbit right ventricular strips, KCl-induced aortic ring contraction, and Ca-45(2+) uptake in K+-depol arized cultured rat cardiomyocytes. Amiodarone completely inhibited my ocardial contraction (EC(50) = 1.7 mu M), completely antagonized depol arization-induced aortic ring contraction (EC(50) = 24 nM), and signif icantly reduced (29% vs. control) Ca-45(2+) uptake into cultured cells . The calcium channel blocking effects of amiodarone may contribute si gnificantly to its pharmacologic profile.