EFFECTS OF THE ADMINISTRATION OF EPSILON AMINO CAPROIC ACID ON CATECHOLAMINE AND SEROTONIN LEVELS IN THE RAT AND DOG

¹ Department of Chemical Pharmacology, Experimental Therapeutics Research, Lederle Laboratories, American Cyanamid Company, Pearl River, New York

The effects of the administration of epsilon amino caproic acid (EACA) on catecholamine and serotonin levels in the rat and dog were studied. Administration of EACA (500 mg/kg or 2000 mg/kg, orally) causes a depletion of norepinephrine in the rat heart, with several days being required for repletion; EACA at 500 mg/kg has no effect on the catecholamine or serotonin content of the brain or catecholamines in the adrenals. Of the various administered compounds structurally related to EACA none were as active as EACA in causing norepinephrine depletion from the rat heart. 5-Amino-1-pentanol and 6-amino hexanoic acid methyl ester hydrochloride show some depleting activity whereas 6-acetamido hexanoic acid, 6-dimethyl-amino hexanoic acid ethyl ester, 5-amino valeric acid hydrochloride or 6-ureido hexanoic acid show no appreciable activity. Pretreatment of the rat with the monoamine oxidase inhibitor, iproniazid, reduces the decline in norepinephrine content of the heart caused by administered EACA or reserpine. Bretylium prevents completely the depleting action observed after administered EACA or guanethidine and partially that of reserpine. Administered EACA causes a large decline in the endogenous norepinephrine content of the left atrium of the dog and no decrease in the endogenous catecholamines in the adrenals. Subendocardial hemorrhages are observed in EACA- treated dogs. The results obtained with EACA are compared with known depletors of pharmacologic interest.