(±)-1-(3,4,5-trimethoxybenzys)-1,2,3,4-tetrahydroisoquinoline(TMI)誘導体の血管拡張作用

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概要

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• Effects of (±) -1- (3, 4, 5-trimethoxybenzyl) -1, 2, 3, 4-tetrahydroisoquinoline (TMI) derivatives with hydroxy groups at the A ring were investigated on the common carotid blood flow and cyclic 3', 5'-adenosine monophosphate phosphodiesterase (PDE) activity of the isolated carotid artery in dogs. Results were compared to those of isoproterenol and papaverine. When administered into the common carotid artery, isoproterenol produced the most potent vasodilating activity and the potency was followed by those of 6, 7-dihydroxyl, 5, 7-dihydroxyl, 5, 6, 7-trihydroxyl, 6, 7, 8-trihydroxyl, 7-hydroxyl, 5-hydroxyl, 6-hydroxyl, 5, 6-dihydroxyl, TMI, 8-hydroxyl, papaverine, 6, 8-dihydroxyl, 7, 8-dihydroxyl, 5, 8-dihydroxyl analogues in decreasing order. Vasodilating actions of 6, 7-dihydroxyl, 5, 7-dihydroxyl, 5, 6, 7-trihydroxyl, 6, 7, 8-trihydroxyl and 7-hydroxyl analogues were almost abolished by propranolol, while those of 8-hydroxyl, 6, 8-dihydroxyl and 7, 8-dihydroxyl analogues were little affected by propranolol. In the TMI derivatives, the inhibition caused by propranolol became more pronounced when the vasodilating activity was more potent. Inhibitory effects of the TMI derivatives on the PDE activity in the supernatant of homogenate of the common carotid artery were weaker than those of papaverine, but were stronger than those of isoproterenol. The TMI derivatives that exhibited potent inhibitory effects of PDE activity had a tendency to show weak vasodilating action. These results suggest that the vasodilating action of the TMI derivatives cannot be ascribed to their inhibitory action of PDE activity but rather is mainly due to their β-syrnpathomimetic action and that the hydroxy group at position 7 is important for manifestation of β-sympathomimetic action, which is attenuated when the hydroxy group is presented at position 8.

• 社団法人 日本薬理学会の論文

著者

• 池沢 一郎

  Research Laboratories Tanabe Seiyaku Co. Ltd.

• 伊藤 信夫

  田辺製薬 (株) 有機化学研究所

• 池沢 一郎

  田辺製薬 (株) 総合研究所

• 竹永 秀幸

  田辺製薬 (株) 総合研究所

• 佐藤 匡徳

  田辺製薬 (株) 総合研究所

• 中島 宏通

  田辺製薬 (株) 総合研究所

• 清本 昭夫

  田辺製薬 (株) 総合研究所

• 伊藤 信夫

  田辺製薬 (株) 総合研究所

関連論文

• Studies on 1,2,3,4-Tetrahydroisoquinolines. IV. β-Adrenoceptor Activity and Absolute Stereochemistry of (-)-5,7-Dihydroxy-1-(3,4,5-trimethoxybenzyl)-1,2,3,4-tetrahydroisoquinoline
• Studies on 1,2,3,4-Tetrahydroisoquinolines. III. Syntheses and β-Adrenoceptor Activities of Methyl Derivatives of Trimetoquinol
• Studies on 1,2,3,4-Tetrahydroisoquinolines. II. A One-pot Synthesis of 1-Arylmethyl-1,2,3,4-tetrahydroisoquinolines from an Isoquinolinium Salt
• Studies on 1,2,3,4-Tetrahydroisoquinoline Derivatives. I. Syntheses and β-Adrenoceptor Activities of Positional Isomers of Trimetoquinol with Respect to Its 6,7-Dihydroxyl Groups
• 新しい還元剤 : 水素化アシルオキシホウ素ナトリウム
• (−)-1-(3, 4, 5-trimethoxybenzyl)-7-hydroxy-1, 2, 3, 4-tetrahydroisoquinoline HCl(l-MTI)の気管支拡張作用
• （−）-1-（3,4,5-trimethoxybenzyl）-5,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline HCl(l-DTI)の気管支ならびに心臓血管系に対する作用
• (±)-1-(3, 4, 5-trimethoxybenzyl)-6-hydroxy-1, 2, 3, 4-tetrahydroisoquinoline hydrochloride (CV-705) の麻酔犬における血管拡張作用
• (±)-1-(3,4,5-trimethoxybenzys)-1,2,3,4-tetrahydroisoquinoline(TMI)誘導体の血管拡張作用

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