Alterations in drug transport in resistant Trypanosoma congolense.

The transport of isometamidium chloride (Samorin) in Trypanosoma congolense which were either sensitive or resistant to this widely used trypanocide was studied in vitro. Significantly lower amounts of drug were accumulated over time by resistant than by sensitive trypanosomes. While no direct evidence could be obtained, indirect observations implied the involvement of an increased efflux of drug from the resistant trypanosomes. In both the resistant and sensitive parasites, drug transport was found to be mediated by an energy-dependent, specific process, presumably receptor-mediated. However, the specificity of the putative receptors was altered in the drug-resistant parasites. It is proposed that an alteration or replacement of a specific receptor in isometamidium chloride-resistant T. congolense results in an increased efflux of the drug and that this increased efflux at least partially mediates the reduction in sensitivity to the compound.