The chemotherapy of rodent malaria, XXXVIII

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Abstract
In addition to their blood schizontocidal action on Plasmodium berghei in vivo, two Mannich bases WR 194,965 and 228,258 are also active against chloroquine-sensitive and chloroquine-resistant lines of P. falciparum in vitro. The response of the lines to each drug differs but shows no correlation in either case with response to chloroquine. The 8-aminoquinoline WR 225,448 is also active against P. falciparum in vitro but at much higher concentrations than the Mannich bases. Application of the ‘chloroquine-induced pigment clumping (CIPC) test’ and the study of ultrastructural changes induced in P. berghei in drug-treated mice indicate that WR 194,965 has a mode of action somewhat resembling that of quinine. WR 228,258 in vitro shows a chloroquine-like effect, but not in vivo, suggesting that its mode of action in vivo is different from that of chloroquine. WR 225,448 has no action in the CIPC in vitro and affects primarily mitochondria of the parasites in vivo. It probably acts through a metabolite. Both pre-erythrocytic and erythrocytic stages of rodent malaria parasites are affected by WR 225,448.