Pharmacological Studies on Xanthine Derivatives (I) Action on Coronary Blood flow

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The effect of more than 60 amino, oxy, aminoxy xanthine derivatives on coronary blood flow were tested by the left coronary cannulation method in dogs. The coronary dilating effect of these derivatives are shown by potency indices with theophylline ethylenediamine (TE) as 1. An interesting relation was revealed between chemical structure and coronary dilating action : comparison between theophylline derivatives and theobromine derivatives shows that the former are more potent than the latter, and comparison between 7 (γ-alkylaminopropyl)-, 7 (β-alkylaminoethyl)- and 7 (γ-alkylamino-β-oxypropyl) theophyllines shows that the last is most potent, followed by the first and the second in that order. Comparison between the number of carbon atoms substituted in the amino group at γ-position in 7 (γ-alkylamino-β-oxypropyl) theophylline shows that as the number of carbon atoms increase, there is a corresponding rise in potency but that after 4 carbons potency begins to decrease, while esterification by benzoic acid or acetic acid enhances coronary dilating activity. From these relations, several new active xanthine derivatives were found to be 3 to 4 times more active than TE. Their chemical structures are 7 (γ-dipropyl (or dibutyl)-amino-β-hydroxy (or benzoyloxy, acetoxy) propyl) theophylline. The antagonistic effect of Vasopressin and TH-24 (1), a typical potent compound, on the coronary blood flow and electrocardiographic pattern were tested. Coronary contraction and elevation of ST segment and T wave of Vasopressin 0.1 u/10sec was almost completely suppressed by simultaneous injection of TH 24 (1) 10mg-3mins.
社団法人日本循環器学会の論文
1962-05-20

Pharmacological Studies on Xanthine Derivatives (I) Action on Coronary Blood flow

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