1 . The administration of 2,4-diamino-5-(3',4'-dichlorophenyl)-6-methylpyrimidine (50-197) and 2,4-diamino-5-(3',4'-dichlorophenyl) pyrimidine (50-11) to mice and rats produced delayed effects characteristic of folic acid deficiency; 50-197 amid 2,4-diamino-5-p-chlorophenyl-6-ethylpyrimidine (50-63) produced similar effects in dogs. LD50 values have been calculated.

2. The diaminopyrimidines caused ileitis amid colitis with diarrhea in mice, rats, and dogs, and stomatitis in dogs; animals lost weight and became dehydrated. Microscopic changes found in gastrointestinal tract, lymphatic tissue, and bone marrow have been described.

3. The hematologic manifestations observed were (a) granulocytopenia and reticulocytopenia in rats and dogs; there was a relatively less severe lymphocytopenia, (b) alterations in dog marrow which included an appreciable proportion of erythroid development via the megaloblast series, numerous and varied mitotic abnormalities, nuclear fragments, giant metamyelocytes, hypersegmented polymorphonuclear cells and a change its nuclear chromatin of myeloid series corresponding to megaloblastosis in erythroid development.

4. Doses of the diaminopyrimidines in excess of the LD50 produced convulsions in mice and rats (50-197 and 50-11); acute convulsant effects were also produced in cats given 50-197 and in dogs given 50-63. This acute convulsant actions could be prevented by means of anesthetic barbiturates. It is a property of alkyl substituted 2,4-diaminopyrimidines and 2-methyl-4-aminopyrimidines and is not specifically related to anti-folic activity.

5. The delayed death of some, but not all, mice following the diaminopyrimidines could be prevented by the simultaneous administration of citrovorum factor. This suggests, on the analogy of 4-amino-PGA and PGA, that there might be another factor or factors its the folic-folinic acid reaction chain as yet unidentified in cells.

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