Beta-blocking Potency and Selectivity of Bopindolol and Its Two Metabolites for β_1-and β_2-Adrenergic Receptors as Assessed by Radioligand Binding Assay
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概要
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Using a radioligand binding assay, we assessed the affinity and selectivity of the antagonistic effects of bopindolol (4-(benzoyloxy-3-tert-butylaminopropyl)-2-methylindole hydrogenmalonate) and its two metabolites, (18-502,(4-(3-tert-butylamino-2-hydroxypropoxy)-2-methyl indole) and 20-785,(4-(3-tert-butylaminopropoxy)-2-carboxyl indole)), for β_1-and β_2-adrenoceptors and on 5HT_<1B>-receptors in rat brain and heart. In addition, we also determined the pA_2 values of these agents for their antagonistic effects toward positive chronotropic and inotropic actions (β_1-adrenoceptors) and for their antagonistic effects toward isolated tracheal relaxation (β_2-adrenoceptors), using isoproterenol as an agonist. The data showed that bopindolol was more selective for β_2-adrenoceptors than for β_1-adrenoceptors and 5HT_<1B>-receptors, but its two metabolites (18-502 and 20-785) did not have significant selectivity for β_1-and β_2-adrenoceptors, using both [^3H]CGP12177 and [^<125>I] ICYP ([^<125>I] iodocyanopindolol) bindings. In contrast, the results from pharmacological assessment for antagonistic potencies, using atria and trachea, showed that bopindolol and its two metabolites did not have significant selectivity on β_1-and β_2-adrenoceptors. A major metabolite of bopindolol, 18-502,had higher pK_1 and pA_2 values for β-adrenoceptors and 5HT_<1B>-receptors than those of bopindolol and 20-785. These results indicate, first, that a radioligand binding assay for the assessment of the selectivity of bopindolol and its two metabolites for β_1-and β_2-adrenoceptors is more effective than pharmacological experiments, and that there is a possibility that its two metabolites also contribute to the strong β-blocking action of bopindolol.
- 公益社団法人日本薬学会の論文
著者
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NAGATOMO Takafumi
Department of Pharmacology, Niigata University of Pharmacy and Applied Life Sciences
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Nagatomo T
Dep. Of Pharmacology Fac. Of Pharmaceutical Sciences Niigata Univ. Of Pharmacy And Applied Life Scie
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TSUCHIHASHI HIROSHI
Department of Surgery, Department of Medicine, Shiga University of Medical Science
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HOSOHATA Yoshiaki
Department of Pharmacology, Niigata College of Pharmacy
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Hosohata Yoshiaki
Department Of Pharmacology Niigata College Of Pharmacy
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Kinami Junji
Department Of Pharmacology Niigata College Of Pharmacy
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Sakuma Noriko
Department Of Pharmacology Niigata College Of Pharmacy
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AKASHI Hirofumi
Department of Pharmacology, Niigata College of Pharmacy
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Nagatomo Takafumi
Department Of Pharmacology Faculty Of Pharmaceutical Sciences Niigata University Of Pharmacy And App
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Tsuchihashi Hiroshi
新潟薬科大学 薬理
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Tsuchihashi Hiroshi
Department Of Pharmacology Niigata College Of Pharmacy
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Namikawa Tomoko
Biological Res. Dep. Sawai Pharmaceutical Co. Ltd.
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