The chemotherapy of rodent malaria XXXVI

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Abstract
Light microscope and ultrastructural studies show that WR 225,448, an 8-aminoquinoline related to primaquine, causes substantial damage to developing pre-erythrocytic (EE) schizonts of Plasmodium yoelii yoelii in the liver of young rats. In addition to lesions of the mitochondria and nuclear membranes, secretory granules in the parasite fail to reach the surrounding host cell cytoplasm across the parasite membrane. The effective dose of WR 225,448 is much lower than that of primaquine. However, hepatic damage is also seen in treated animals. This may be the summation of damage produced by the experimental inoculation of a large quantity of infective salivary gland tissue from mosquitoes (which is also seen in untreated animals) plus toxic effects of the drug itself. Particular attention would have to be directed to this aspect in preclinical toxicity testing of the compound.

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