Anti-inflammatory effect of antiplasmin agents,ε -aminocaproic acid and trans-4-aminomethyl-cyclohexane carboxylic acid, in rats

1. Both EACA and AMCHA clearly showed an anti-inflammatory effect, by intravenous, intramuscular, or oral route, against inflammatory edema produced in rats by intracutaneous injection of rabbit's anti-rat serum, carrageenin, histamine, serotonin, or bradykinin, as tested by the punch method. 2. The two compounds also showed inhibitory action against the cotton pellet granuloma when used in a larger dose. 3. There was virtually no difference between the two compounds in their anti-inflammatory activity, in spite of the fact that antiplasmin activity of AMCHA is evidently greater than that of EACA. In addition, there was no increase in fibrinolysis at the site of antiserum inflammation in rats. Therefore, it would be difficult to presume that the anti-inflammatory action of these compounds is due to their antiplasmin activity. 4. Salicylates, pyrazolidine derivatives, and non-steroidal antiinflammatory agents like flufenamic acid inhibited degranulation of isolated rat mast cells induced by compound 48/80 and also inhibited ATP-32Pi exchange reaction in rat liver mitochondria, but such actions were not observed in EACA or AMCHA. 5. Anti-inflammatory effect of EACA and AMCHA did not decrease after adrenalectomy but did become weak in hypophysectomized rats. EACA did not increase blood sugar level in normal rats so that its antiinflammatory action is not due to hyperglycemia, and the effect of hypophysectomy may not be correlated to carbohydrate metabolism. 6. Anti- inflammatory effect of EACA and AMCHA appeared more rapidly after intramuscular or oral administration than by intravenous injection but the effect was not fortified after their in vitro incubation with tissues of stomach, intestine, or liver.