Bopindolol Is a Slowly Dissociating β_1-Adrenoceptor Antagonist When Compared to Other β-Blockers

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概要

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• This study used radioligand binding assay methods and pharmacological experiments to examine whether bopindolol, possessing a long-lasting action in addition to potent β-adrenoceptor antagonistic effects, is a slowly dissociating antagonist. In addition, the slow dissociation of two of its metabolites, 18-502 (4-(3-tert-butylamino-2-hydroxypropoxy)-2-methyl indole) and 20-785 (4-(3-tert-butylaminopropoxy)-2-carboxyl indole), which have potent β-blocking activities, was also assessed. The blockade of ^3H-CGP12177 binding sites in rat heart and brain induced by pindolol was readily reversed by washing, whereas this inhibition by bopindolol and 18-502 was not easily reversed by washing. In addition, specific bindings of the hearts of the treatment animals with 20-785,atenolol, (±) propranolol, nadolol and celiprolol and of washout were 86.7,78.8,77.5,82.3 and 79.9% of the control, respectively. These blockades by the treatment of each drug and washout in the brain were, however, lower than those in the hearts. On the other hand, when the left and right atria were pretreated with propranolol, bopindolol and 18-502,the inotropic and chronotropic actions of isoprenaline were inhibited by these drugs even though they were not present in the extracellular medium. Pretreatment with 20-785,atenolol and nadolol was readily reversed for both inotropic action and chronotropic rate, and inhibition by celiprolol and pindolol remained at 25% of the control at 240 min after treatment with these drugs. A good correlation between inhibitory binding percentage in the hearts and inhibitory inotropic or chronotropic actions were observed, although it was not observed in the brain. Thus, these results suggest that bopindolol and 18-502 are slowly dissociating β-adrenoceptor antagonists and this property may explain its long-lasting anti-hypertensive effects when compared to other β-blockers.

• 公益社団法人日本薬学会の論文
• 1995-08-15

著者

• 服部 薫

  新潟薬大薬理

• 佐々木 佳子

  Department of Pharmacology, Niigata College of Pharmacy

• 長友 孝文

  Department of Pharmacology, Niigata College of Pharmacy

• 長友 孝文

  新潟薬科大学薬学部薬理学教室

• 佐々木 佳子

  新潟薬科大学薬理学教室

• 鈴木 潤

  アムジェン(株)開発本部

• 長友 孝文

  新潟薬科大学・薬・薬理

• 細機 好章

  Department of Pharmacology, Niigata College of Pharmacy

• 細機 好章

  アリゾナ大学医学部薬理学教室

• 沈 洋

  Department of Pharmacology, Niigata College of Pharmacy

• 服部 薫

  Department of Pharmacology, Niigata College of Pharmacy

• 鈴木 潤

  Research and Development Division, Sandoz Pharmaceuticals, Ltd.

• 沈 洋

  Department Of Pharmacology Niigata College Of Pharmacy

• Shen Yang

  Department Of Pharmacology Niigata College Of Pharmacy

• Kaoru Hattori

  Department Of Pharmacology Niigata College Of Pharmacy

• 長友 孝文

  Department Of Pharmacology Faculty Of Pharmaceutical Sciences Niigata University Of Pharmacy And App

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