Pharmacological Studies on Xanthine Derivatives (II) ACTION ON PERIPHERAL VESSELS AND ACUTE TOXICITY

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The effect of 47 aminoxy and amino-xanthine derivatives on blood flow of the femoral artery (f. a.) and toxicity in mice and rats of some of these compounds were tested. Comparing the effects of the compounds on f. a. and on coronary artery (c. a.), the former are more effective than the latter. The minimum effective dose of theophylline ethylenediamine (TE) and these compounds on f. a. is about 0.2mg, and that on c. a. about 1.0mg. But the potency indices of these compounds on f. a. are inclined to be smaller than on c. a. With regard to relationship between effect and chemical structure, although the effect on c. a. differs from that on f. a. in the little details, the correlation coefficient is 0.752, which seemed to indicate that both blood vessels react in a similar manner to the compounds. The relationship between toxicity and chemical structure were studied with these interesting revelations : (1) In the monoalkylaminoxypropyl xanthine derivatives, theobromine derivatives are more toxic than theophylline derivatives. (2) When C-atoms of the alkyl radicals replaced at amino radical increased, toxicity increased in direct proportion. (3) In the β-alkylaminoethyl theophylline derivatives, toxicity was strongest when the alkyl at terminal N was methyl, becoming less toxic in the case of ethyl and n-propyl in that order. And the ratio of toxicity in intraperitoneal and intravenous injection were distributed from near 1.1 to near 6.8, indicating that the compounds are well absorbed.
社団法人日本循環器学会の論文
1962-05-20

Pharmacological Studies on Xanthine Derivatives (II) ACTION ON PERIPHERAL VESSELS AND ACUTE TOXICITY

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