RT Journal Article
SR Electronic
T1 PROLONGED ADMINISTRATION OF LARGE DOSES OF ACETANILID IN MONKEYS WITH SPECIAL REFERENCE TO BLOOD CHANGES
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1
OP 13
VO 68
IS 1
A1 PAUL K. SMITH
YR 1940
UL http://jpet.aspetjournals.org/content/68/1/1.abstract
AB Monkeys were given large daily doses of acetanilid varying from 100 to 600 mgm. per kilogram for periods from nine to eighteen weeks. These doses are far in excess of any probably therapeutic quantities both in the size of a single dose and in the chronic use. Examination of the feces demonstrated complete absorption of the drug. Some tolerance probably developed toward the depressant effect on voluntary activities; but studies of the respiratory changes after electrical and mechanical stimuli did not reveal any tolerance toward the analgesic effects. No evidence of addiction was found. No electrocardiographic abnormalities could be demonstrated. The erythrocyte count and volume and total hemoglobin were significantly reduced in the animals receiving 500 mgm. acetanilid per kilogram daily for two or more months, but all were near normal in animals receiving 100 mgm. per kilogram for eighteen weeks. In most of the animals significant amounts of hemoglobin occurred in non-oxygen combining forms. In the five animals studied after the drug was discontinued, these altered forms of hemoglobin had largely disappeared. Pathological examinations revealed no abnormalities that might be attributed to the administration of the drug except in the animals receiving 500 mgm. of the drug for fifteen weeks. In these the livers and spleens contained moderately large amounts of an hemosiderin-like pigment and the bone marrow showed some hyperplasia of the red cell-forming elements and contained numbers of phagocytes containing yellow pigment and fragments of red cells. These findings were interpreted as evidence of the destruction and regeneration of erythrocytes.