BRONCHODILATING ACTIONS OF (±)-1-(3, 4, 5-TRIMETHOXY-BENZYL)-I, 2, 3, 4-TETRAHYDROISOQUINOLINE (TMI) DERIVATIVES IN ANESTHETIZED CATS

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Bronchodilating actions of 7-hydroxy(I), 5, 7-dihydroxy(II), 5, 6, 7-trihydroxy (III) and 6, 7.8-trihydroxy(IV)-()-I-(3, 4, 5-trimethoxybenzyl)-12, 3, 4-tetrahydroisoquinolinc (TMI) were investigated in anesthetized cats and results were compared to those of AQ-110 (6, 7-dih)droxy-TMI) and isoproterenol. TMI derivatives given intravenously suppressed the bronchoconstriction induced by serotonin. These compounds also caused an increase in heart rate and a decrease in diastolic pressure. All of these actions sere inhibited by pretreatment vvith propranolol, suggesting that they were classified as β-sympathominictics. Bronchodilating activities of AQ-110, I, II, III and IV were 1 2.6, 136, 1 4.0, 1 7.7 and 1 23 that of isoproterenol, respectively. When compared with isoproterenol, I and the other TMI derivatives were about 9 and 2 times more potent in producing bronchodilation than in increasing heart rate. On the other hand, the bronchodilating activities of I, II and AQ-110 were 2-3 times as great as their depressor activities, while III and IV had no selectivity. When administered into the duodenum, II was the most potent in producing bronchodilation and the potency was followed by these of AQ-110, I, III, isoproterenol and IV in decreasing order. Duration of the bronchodilating action of TMI derivatives administered via either intravenous or intraduodenal route was considerably longer than that of isoproternol; especially I and II were long-acting. These results suggest that I and II exhibits a greater absorption efficiency or intraduodenal bioavailability than the other compounds tested.
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BRONCHODILATING ACTIONS OF (±)-1-(3, 4, 5-TRIMETHOXY-BENZYL)-I, 2, 3, 4-TETRAHYDROISOQUINOLINE (TMI) DERIVATIVES IN ANESTHETIZED CATS

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