Differential sensitivity of erythrocytic stages of the rodent malaria parasite Plasmodium chabaudi chabaudi to dioncophylline B, a highly active naphthylisoquinoline alkaloid

Four-week-old OF1 mice, infected with synchronized Plasmodium chabaudi chab audi blood forms, were intraperitoneally injected with the naphthyl isoquin oline alkaloid dioncophylline B (10 mg kg(-1) day(-1)) at three consecutive days. The respective groups were treated when rings, trophozoites, and sch izonts were predominant. Microscopical observations of thin blood smears we re made every two hours after the start of the experiment. A clear dependen cy of the effectiveness of dioncophylline B treatments on the timing of dru g administration was demonstrated. Based upon the evolution of total parasi taemia and the survival rates, it was concluded that ring stages are insens itive to dioncophylline B, while the drug is highly effective when given at the trophozoite stage and partially effective when given at the schizont s tage. Dioncophylline B seems to act by inhibiting the haemozoin degradation , as indicated by pigment clumping, and by impairing the segmentation of sc hizonts.