PT  - JOURNAL ARTICLE
AU  - Courchesne, William E.
TI  - Characterization of a Novel, Broad-Based Fungicidal Activity for the Antiarrhythmic Drug Amiodarone
AID  - 10.1124/jpet.300.1.195
DP  - 2002 Jan 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 195--199
VI  - 300
IP  - 1
4099  - http://jpet.aspetjournals.org/content/300/1/195.short
4100  - http://jpet.aspetjournals.org/content/300/1/195.full
SO  - J Pharmacol Exp Ther2002 Jan 01; 300
AB  - 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. AIDSacquired immunodeficiency syndromeSD0.17% (w/v) Difco yeast nitrogen base without amino acids and ammonium sulfate, 0.4% (w/v) ammonium sulfate, 2% (w/v) glucoseDMSOdimethyl sulfoxideHIVhuman immunodeficiency virus