EFFECT OF VERAPAMIL ON ANTITRYPANOSOMAL ACTIVITY OF DRUGS IN MICE

The effects of verapamil on drug responses of Trypanosoma brucei brucei were studied to determine whether drug resistance of this organism could be related to expression of a drug resistance gene as has been described for drug-resistant cancer cells and malaria. Concomitant administration of verapamil during treatment of two different strains of the parasite with ethidium or berenil resulted in enhancement of the drug effect as shown by increased formation of dyskinetoplastic organisms, increased rates of clearing of the parasites from the blood, and by enhanced survival of infected mice. Verapamil treatment was associated with increased intracellular accumulation of drug, as shown by fluorescence of cells exposed to ethidium or DAPI, a fluorescent surrogate for berenil. These results suggest the importance of exploring the expression of the multiple drug-resistance gene in this series of parasites.