Trypanosoma cruzi: possible control of parasite transmission by blood transfusion using amphiphilic cationic drugs.
About 200 clinically used amphiphilic cationic drugs have been shown to be active in vitro against Trypanosoma cruzi at concentrations of less than or equal to 1 mM. Activity against epimastigote and trypomastigote forms was similar, and in both cases the most potent drugs were litracene, maprotiline, thioproperazine, and the acridines: acranil, aminacrine, and mepacrine. Fluorescence microscopy demonstrated that epimastigotes rapidly accumulate acridines initially in discrete subcellular organelles. The amount of drug incorporated during 15 min of incubation was sufficient to produce subsequent lysis of both trypomastigotes and epimastigotes within 24 hr at 4 C. Trypanocidal activity was dependent on the extracellular pH (optimum greater than or equal to 8) and drug exposure time, but was independent of red blood cell density, serum dilution, and temperature (4 to 37 C). Despite their trypanocidal activity, amphiphilic cationic drugs appear to have no significant effect on the energy state of red blood cells at a concentration of 1 mM. These drugs have a possible role in the prevention of Chagas' disease by blood transfusion.
D000609:Aminoacridines / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000981:Antiprotozoal Agents / Q000378:metabolism / Q000494:pharmacology*; D002412:Cations / Q000378:metabolism / Q000494:pharmacology; D014355:Chagas Disease / Q000517:prevention & control / Q000635:transmission; D003593:Cytoplasm / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D051379:Mice; D008805:Mice, Inbred A; D008856:Microscopy, Fluorescence; D013997:Time Factors; D065227:Transfusion Reaction; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure
D000609:Aminoacridines; D000981:Antiprotozoal Agents; D002412:Cations