Allosteric modulation of [3H]nitrendipine binding to cardiac and cerebral cortex membranes by amiodarone

Nokin, P.; Clinet, M.; Swillens, S.; Delisée, C.; Meysmans, L.; Chatelain, P.

Journal of Cardiovascular Pharmacology 8(5): 1051-1057

1986


ISSN/ISBN: 0160-2446
PMID: 2429079
DOI: 10.1097/00005344-198609000-00025
Accession: 039217200

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Abstract
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.