The metabolic effects of 4-aminopteroylglutamic acid in the guinea pig.

The announcement of the synthesis of pteroylglutamic acid by Angier, Boothe, Hutchings, Mowat, Semb, Stokstad, SubbaRow, Waller, Cosulich, Fahrenbach, Hultquist, Kuh, Northey, Seeger, Sickels & Smith (1945) and reports of its effectiveness in the treatment of the haematological changes of pernicious anaemia were followed by the production of numerous synthetic analogues and derivatives, some of which were shown to be of value in the treatment of leukaemia and allied disorders. The synthesis of a potent substance of this nature, 4-aminopteroylglutamic acid (aminopterin), was announced by Seeger, Smith & Hultquist (1947). Attempts to produce anaemia in animals by inducing folic-acid deficiency in various ways have been reviewed by Girdwood (1950), who refers to the use of 4-aminopteroylglutamic acid for this purpose in mice, rats, chicks, dogs and guinea-pigs. The reports suggest that in animals other than the guinea-pig the substance produces anaemia and leucopenia, and that these changes can be reversed with difficulty by high dosage of pteroylglutamic acid. Minnich & Moore (1948) produced a hypoplastic anaemia and agranulocytosis in guinea-pigs using 4-aminopteroylglutamic acid, but these changes could not be prevented by the simultaneous administration of liver extract or of pteroylglutamic acid. The main purpose of the present investigation was to explore further the possibility of reversing the haematological changes induced by 4-aminopteroylglutamic acid in the guinea-pig, and to assay the livers of the animals for their content of pteroylglutamic acid and of vitamin B12,