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Research ArticleCELLULAR AND MOLECULAR

Characterization of a Novel, Broad-Based Fungicidal Activity for the Antiarrhythmic Drug Amiodarone

William E. Courchesne
Journal of Pharmacology and Experimental Therapeutics January 2002, 300 (1) 195-199; DOI: https://doi.org/10.1124/jpet.300.1.195
William E. Courchesne
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Abstract

Fungal infections are common in patients with acquired immunodeficiency syndrome and pose a major health management problem. There is a need for identification of new antifungals to complement the limited current repertoire and to combat newly arising resistant fungal strains. We have identified a novel antifungal activity for the antiarrhythmic drug amiodarone. Extensive characterization of this activity shows that amiodarone exhibits a growth inhibition for several diverse fungi, including species of Cryptococcus,Saccharomyces, Aspergillus,Candida, and Fusarium. The antifungal activity was shown to be fungicidal; Cryptococcus neoformans treated with amiodarone lost viability within hours of drug exposure. Growth inhibition could be suppressed by addition of very high concentrations (10 mM) of calcium to the medium, suggesting that disruption of calcium homeostasis was involved in the antifungal activity. Direct measurement of radiolabeled calcium efflux showed that addition of amiodarone resulted in an immediate efflux of cellular calcium. In conclusion, amiodarone displays broad-based fungicidal activity and may be acting in part by perturbing the calcium balance.

Footnotes

  • This study was supported by National Science Foundation Grant MCB-9513713 (to W.E.C.).

  • Abbreviations

    AIDS
    acquired immunodeficiency syndrome
    SD
    0.17% (w/v) Difco yeast nitrogen base without amino acids and ammonium sulfate, 0.4% (w/v) ammonium sulfate, 2% (w/v) glucose
    DMSO
    dimethyl sulfoxide
    HIV
    human immunodeficiency virus
    • Received September 10, 2001.
    • Accepted October 8, 2001.
    • The American Society for Pharmacology and Experimental Therapeutics
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    Journal of Pharmacology and Experimental Therapeutics: 300 (1)
    Journal of Pharmacology and Experimental Therapeutics
    Vol. 300, Issue 1
    1 Jan 2002
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    Research ArticleCELLULAR AND MOLECULAR

    Characterization of a Novel, Broad-Based Fungicidal Activity for the Antiarrhythmic Drug Amiodarone

    William E. Courchesne
    Journal of Pharmacology and Experimental Therapeutics January 1, 2002, 300 (1) 195-199; DOI: https://doi.org/10.1124/jpet.300.1.195

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    Research ArticleCELLULAR AND MOLECULAR

    Characterization of a Novel, Broad-Based Fungicidal Activity for the Antiarrhythmic Drug Amiodarone

    William E. Courchesne
    Journal of Pharmacology and Experimental Therapeutics January 1, 2002, 300 (1) 195-199; DOI: https://doi.org/10.1124/jpet.300.1.195
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