EFFECT OF VERAPAMIL ON ANTITRYPANOSOMAL ACTIVITY OF DRUGS IN MICE

The effects of verapamil on drug responses of Trypanosoma brucei bruce i were studied to determine whether drug resistance of this organism c ould be related to expression of a drug resistance gene as has been de scribed for drug-resistant cancer cells and malaria. Concomitant admin istration of verapamil during treatment of two different strains of th e parasite with ethidium or berenil resulted in enhancement of the dru g 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 fluore scence of cells exposed to ethidium or DAPI, a fluorescent surrogate f or berenil. These results suggest the importance of exploring the expr ession of the multiple drug-resistance gene in this series of parasite s.