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

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 n...

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Bibliographic Details
Published in:The Journal of pharmacology and experimental therapeutics 2002-01, Vol.300 (1), p.195-199
Main Author: Courchesne, William E
Format: Article
Language:English
Subjects:
Amiodarone - pharmacology
Anti-Arrhythmia Agents - pharmacology
Antifungal Agents
Calcium - metabolism
Cations - pharmacology
Cryptococcus neoformans - drug effects
Culture Media
Fungi - drug effects
Fungi - growth & development
Microbial Sensitivity Tests
Saccharomyces cerevisiae - drug effects
Saccharomyces cerevisiae - metabolism
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Summary: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.
ISSN:0022-3565
1521-0103
DOI:10.1124/jpet.300.1.195