ABSTRACT
Quinine and its congener, chloroquine, have been used as antimalarial drugs for many years, yet their definitive mode of action is not completely understood (Ginsburg and Geary, 1987). The quest for the molecular mode of antimalarial action has followed the natural dialectic of scientific research, yielding periodically novel putative mechanisms that have subsequently been rejected after experimental testing. At the present time it seems that the lysosomotropic hypothesis is reigning (Krogstad and Schlesinger, 1987; Schlesinger et al., 1988). Since this hypothesis must also be compatible with drug resistance and its reversal by various agents, I first discuss its merits, then deal with its compatibility with the proposed active drug efflux pump acting in drug resistant parasites. Finally, I discuss the latter in detail to evaluate whether the currently accepted mode of this pump in cancer cells can be extrapolated to drug resistance and its reversal in malaria parasites.
