Abstract
Several isopropylantipyrine (IA) derivatives were synthesized in order to develop their new biological activities and depress the side effects of IA. Among these compounds, especially, ephedrine-IA (EIA) possessed much stronger inhibitory actions to histamine and anaphylactic shocks of isolated guinea pig ileum, rat erythrocyte hemolysis, and polymorphonuclear leukocyte (PMN) chemotaxis than the mixture of IA and ephedrine, other IA derivatives and aminopyrine, but EIA was similar to IA in analgetic and antipyretic actions. LD50 (oral) of EIA is 3.48±0.39 g/kg in mice, and EIA did not show the toxic behavior of ephedrine and any side effects in mice treated for 8 weeks. When 3H-EIA was administered orally to rats, about 30% of the given 3H was absorbed from digestive system in 30 min and about 42% in 6 hr, more than 85% of it was excreted in the feces and urine during 3 days, and about 15% was also excreted in the bile. The highest concentration of 3H in most organs was found 3 hr after oral administration and 3H was concentrated in the small intestine, stomach and liver. About 15% of 3H excreted in urine within 24 hr after the administration was identified as an unaltered 3H-EIA.
