The effect of verapamil alone and in combination with trypanocides on multidrug-resistant Trypanosoma brucei brucei.
Following previous studies of verapamil reversal of multidrug resistance in cancer cells and chloroquine resistance in malaria, the effect of the calcium channel blocker verapamil was investigated on multidrug-resistant and susceptible Trypanosoma brucei brucei. Resistance of cloned parasites to diminazene aceturate (Berenil) and isometamidium chloride (Samorin) was expressed in a cell-free in vitro culture system. Verapamil showed antitrypanosomal activity against both, multidrug-resistant and susceptible trypanosomes at concentrations above 1 micrograms/ml. Verapamil did not reverse multidrug resistance when used at concentrations of 0.1 or 1.0 micrograms/ml in combination with diminazene aceturate or isometamidium chloride. Results obtained in vitro correlate with observations in mice. It is suggested that multidrug resistance in African trypanosomes is due to mechanisms other than those occurring in cancer cells, malaria or South-American trypanosomiasis.
International Laboratory for Research on Animal Diseases, ILRAD, Nairobi, Kenya.
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Kaminsky
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Zweygarth
D000818:Animals; D004133:Diminazene / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D004347:Drug Interactions; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D005260:Female; D008297:Male; D051379:Mice; D010617:Phenanthridines / Q000494:pharmacology / Q000627:therapeutic use; D014344:Trypanocidal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D014346:Trypanosoma brucei brucei / Q000187:drug effects* / Q000254:growth & development; D014353:Trypanosomiasis, African / Q000188:drug therapy*; D014700:Verapamil / Q000494:pharmacology* / Q000627:therapeutic use
D010617:Phenanthridines; D014344:Trypanocidal Agents; C000702:isometamidium chloride; D014700:Verapamil; C003915:diminazene aceturate; D004133:Diminazene