Of Men, Malaria and Megaloblasts

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Abstract
Shortly after the introduction of 2, 4-diamino-5-Pchlorphenyl-6-ethylpyrimidine (pyrimethamine, Daraprim) and related substituted pyrimidines as a new class of antimalarials1 it was found that these agents could induce megaloblastic changes in the bone marrow in man, with peripheral macrocytosis and hypersegmented granuloeytes.2 Studies of man, laboratory animals and folate-dependent microorganisms indicated that in spite of the structural similarity of pyrimethamine to the substituted pyrimidines, the hematologic complications of its use were due to its action as a folate antagonist. The manner by which pyrimethamine impairs folate metabolism has not previously been elucidated.In this issue of the Journal, Waxman and Herbert, . . .