The chemo therapy of rodent malaria part 23 causal prophylaxis part 2 practical experience with plasmodium yoelii nigeriensis in drug screening

Peters, W.; Davies, E. E.; Robinson, B. L.

Data are presented on the causal prophylactic action of about 100 compounds of various types against P. yoelii nigeriensis N67 in mice. Examples are given to show how action against pre-erythrocytic schizonts may be differentiated from action on emerging erythrocytic stages. In a series of thirty-five 8-aminoquinolines, all but 10 showed definite causal prophylactic activity at tolerated doses. The data permit the compounds to be ranked in order of activity and many are more active in this test system than primaquine. Marked causal prophylactic activity is displayed by a variety of quinone structures, several of which show a significant residual action on blood stages. A high level of activity is found in dihydrofolate inhibitors within several chemical classes. Proguanil is more effective as a causal prophylactic than a blood schizontocide in the mouse as in man. Sulfonamides and sulfones are also effective in this system. Causal prophylactic action was detected in a number of experimental compounds including some antibiotics (such as tetracycline and clindamycin). The pyrocatechol RC 12 shows only slight activity at the maximum tolerated dose. Chloroquine, mepacrine, quinine, quinolinemethanols and phenanthrenemethanols are inactive as causal prophylactics. A rodent malaria-mouse model provides a relatively simple model for the screening of drugs for causal prophylaxis and the data so obtained are of relevance to the detection of causal prophylactics against human malaria.