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Amiodarone is a potent calmodulin antagonist

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Summary

The possible interaction between amiodarone, a potent antiarrhythmic and antianginal agent, and calmodulin (CaM) was investigated by three avenues of approach: (a) Effect of amiodarone on cardiac and vascular Ca2+/calmodulin-activated cyclic nucleotide phosphodiesterase (CaM-PDE); (b) Effect on the CaM-activated (Ca2+ + Mg2+)-ATPase from human erythrocytes; (c) Direct interaction between amiodarone and calmodulin measured by the effect of the drug on the fluorescence of 9-anthroylcholine (9AC) bound to calmodulin. Results show that amiodarone did not interact with basal activities of CaM-PDE and other isolated CaM-insensitive PDE forms as well as with (Ca2+ + Mg2+)-ATPase. Amiodarone inhibited calmodulin-activation of aortic CaM-PDE (K i = 650 nM, substrate cGMP) and calmodulin-activation of erythrocyte ghosts (Ca2+ + Mg2+)-ATPase (IC50 = 4.5 μM) in an apparently competitive manner. Amiodarone decreased the fluorescence of the hydrophobic probe 9AC bound to calmodulin (IC50 = 5 μM).

It is concluded that amiodarone is a potent calmodulin antagonist.

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Authors and Affiliations

  1. Sanofi-Labaz Research Center, 1, avenue de Béjar, B-1120, Brussels, Belgium

    P. Nokin, J. P. Blondiaux & L. Jungbluth

  2. CNRS U.A. 600, Faculté de Pharmacie, Université Louis Pasteur, B.P. 10, F-67048, Strasbourg Cédex, France

    P. Schaeffer & C. Lugnier

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  1. P. Nokin
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  2. J. P. Blondiaux
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  3. P. Schaeffer
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  4. L. Jungbluth
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  5. C. Lugnier
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Nokin, P., Blondiaux, J.P., Schaeffer, P. et al. Amiodarone is a potent calmodulin antagonist. Naunyn-Schmiedeberg's Arch. Pharmacol. 339, 367–373 (1989). https://doi.org/10.1007/BF00736049

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  • DOI: https://doi.org/10.1007/BF00736049

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