β-Dimethylaminoethylbenzhydryletherの消長に關する研究

抄録

The metabolic fate of β-dimethylaminoethylbenzhydrylether (Restamin, R.) was studied in guinea pigs, and was compared with that in rabbits and toads. The results obtained were as follows : 1) R. subcutaneously or orally administered was absorbed rapidly. Symptoms of stimulation developed when the levels of R. in the blood exceeded 5 mg per cc. 2) Urinary excretion of R. was also relatively rapid in guinea pigs, and 4.2-23.2 % of the injected dose was excreted in the urine in unchanged form in 24 hours. 3) R. was distributed through all the tissues in guinea pigs, and the highest concentration was found in lungs, and decreasingly in spleen, liver, kidneys and small intestine. 4) The rate of decomposition in slices from the livers of guinea pigs was more rapid than that from other tissues. In toads the decomposition activity was lower than in the other animals and its optimal temperature for decomposition was slightly lower. In the perfusion experiments on the liver and hind legs of toads similar results were obtained.5) The optimal condition for the decomposition of R. was found at 37.5°C and pH 7.4. 6) In the decomposition of R. in liver tissue in the first step the ether linkage was broken down and benzhydrol and dimethylaminoethanol were found as metabolic products. Then benzhydrol was metabolized into an unknown acidic substance, and dimethylaminoethanol was partly metabolized through an unknown route. The antihistaminic and antiacetylcholinic activity were not demonstrated in these metabolic products. 7) The decomposition of R. in the liver slices of guinea pigs was inhibited markedly by some reducing agents, such as cysteine, ascorbic acid or hydroxylamine, and in perfusion experiments on the liver and hind legs of toads, cysteine showed the same effect, but in vivo experiments these reducing agents had no influence.