Takeshi Akimoto

Toxicological studies of 1-[2-(1,3-dimethyl-2-butenylidene)-hydrazino]-phthalazine, a new antihypertensive drug, in mice and rats.

Abstract Budralazine, 1-[2-(1,3-dimethyl-2-butylidene)-hydrazino]-phthalazine, an antihypertensive drug, has been evaluated toxicologically in mice and rats. The acute oral toxicity of budralazine was 10 and 2 times lower in mice and rats, respectively, than that of hydralazine. The oral LD50 values (in grams per kilogram) of budralazine in mice were 2.89 for males and 1.82 for females; in rats they were 0.62 for males and 0.73 for females. After ip or sc administration, the LD50 in both sexes and species was greater than 3.5 g/kg. Repeated oral administration to rats produced anemia as shown by reduction in erythrocyte counts, hemoglobin concentration, and hematocrit, along with increased reticulocyte counts and spleen hemosiderosis, the latter considered to be hemolytic in origin. These changes were rapidly reversible upon cessation of treatment. Other effects included salivation, growth retardation, and very slight degeneration of renal proximal tubular epithelium. Blood chemistry and organ weight parameters were not affected, nor was antinuclear antibody detected. Although similar blood and tissue changes were produced by hydralazine, under these experimental conditions, budralazine has been shown to be approximately half as toxic as hydralazine.