The toxicity of diaminodiphenoxyalkanes.
Representative members of a series of schistosomicidal diaminodiphenoxyalkanes were examined for their toxic effects in laboratory animals. Primary amino-derivatives were, in general, more toxic than secondary methylamino-compounds; tertiary compounds were less toxic than either. Large doses given by mouth or by injection to mice or rabbits produced intravascular haemolysis; the haemoglobin and erythrocyte counts began to increase again about a week after the dose. Mice which had been given large doses of diaminodiphenoxyalkanes developed symmetrical bald patches 2 to 3 weeks after treatment. The exposed skin appeared normal and new fur grew to cover the hairless areas in about 6 weeks. Large doses of drug delayed water diuresis in mice.Many compounds of the series caused visual impairment when given to cats. In order to obtain a quantitative assessment of retinotoxic potency, a method was devised in which the ability of the retina of the frog to resynthesize rhodopsin was measured in treated and control animals. Compounds that produced blindness in cats also inhibited rhodopsin synthesis in frogs; the most toxic compounds were primary amines. Treatment with some tertiary amines caused retinal damage if the drugs were given for long periods. Diaminodiphenoxyalkanes may perhaps interfere in some way with the biological activity of vitamin A. However, toxic effects on the hair and retina were not prevented by supplements of synthetic or natural vitamin A.
D000818:Animals; D000871:Anthelmintics / Q000633:toxicity*; D002415:Cats; D051379:Mice; D011817:Rabbits; D012867:Skin
D000871:Anthelmintics
ANTHELMINTICS/toxicity