A Possible Mode of Action of ‘Paludrine’

Abstract

IN the evolution of the antimalarial drug ‘Paludrine’, the diguanide system was selected because it provided structural features similar to those found in the earlier active pyrimidine compound ‘2666’¹. The biochemistry of the former drug, together with the results obtained in both experimental and clinical therapy, indicate, however, that it is biologically distinct from the prototype molecule. Thus, for example, therapeutic potency is many times greater, and is apparent not only against the erythrocytic but also against the exo-erythrocytic forms of the malaria parasite. Further, ‘Paludrine’ does not show the antagonism for riboflavine exhibited by ‘2666’ (and mepacrine) with respect to the growth of the Lactobacillus casei, an effect that we associate with the formal structural resemblance of the latter drugs to the vitamin, and which may also be connected with their parasiticidal activity.