The chemotherapy ofPlasmodium berghei.II. Antagonism of the action of drugs

The action of pyrimethamine, sulphadiazine, proguanil and its active metabolite CPT, and 2:4-diaminopteridines against infections ofPlasmodium bergheiin mice was antagonized byP–aminobenzoic acid and by pteroylglutamic acid. Antagonism was in some instances detected only whenP–aminobenzoic acid was given in solution in the drinking water as well as being injected subcutaneously. No antagonism was detected with a number of amino acids and nucleic acid derivatives. As all of the above group of drugs can be antagonized byP–aminobenzoic acid and by pteroylglutamic acid, it would seem that they are alike in their mode of action. There must, however, be some differences between the mode of action or absorption of these drugs because species ofPlasmodiumthat are very sensitive to the action of one of these drugs are frequently not very sensitive to the action of others. AsP. bergheiis dependent onp–aminobenzoic acid, it is suggested that it can utilize this compound in the synthesis of pteroylglutamic acid to a greater extent than canP. gallinaceum, and that it resemblesP. knowlesimore than other species ofPlasmodium.