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The possible interaction between the antianginal and antiarrhythmic drug amiodarone and the slow calcium channel was investigated by competition binding experiments in guinea-pig cerebral cortex and rat heart membranes using [3H]nitrendipine as radioligand. Amiodarone displaced specifically bound [3H]nitrendipine from cerebral cortex and cardiac membranes in an apparently competitive manner. In saturation binding experiments, apparent affinity for [3H]nitrendipine progressively decreased with increasing concentrations of amiodarone, whereas maximal binding capacity (Bmax remained unchanged. Both diltiazem and verapamil reversed the inhibitory effect of amiodarone on [3H]nitrendipine binding to cerebral cortex membranes. Together these results suggest that amiodarone exerts a pseudocompetitive inhibition on [3H]nitrendipine binding by acting at a site in allosteric interaction with the 1,4 dihydropyridine binding site associated with the calcium channel. The data are compatible with the existence of a common binding site for diltiazem, verapamil, and amiodarone. These observations are discussed in connection with the pharmacological properties of the drug.
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