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标题：Beta-blocking Potency and Selectivity of Bopindolol and Its Two Metabolites for β1-and β2-Adrenergic Receptors as Assessed by Radioligand Binding Assay
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作者：Noriko SAKUMA ; Hiroshi TSUCHIHASHI ; Yoshiaki HOSOHATA 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：1991
卷号：14
期号：5
页码：250-255
DOI：10.1248/bpb1978.14.250
出版社：The Pharmaceutical Society of Japan
摘要：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 β₁-and β₂-adrenoceptors and on 5HT_1B-receptors in rat brain and heart. In addition, we also determined the pA₂ values of these agents for their antagonistic effects toward positive chronotropic and inotropic actions (β₁-adrenoceptors) and for their antagonistic effects toward isolated tracheal relaxation (β₂-adrenoceptors), using isoproterenol as an agonist. The data showed that bopindolol was more selective for β₂-adrenoceptors than for β₁-adrenoceptors and 5HT_1B-receptors, but its two metabolites (18-502 and 20-785) did not have significant selectivity for β₁-and β₂-adrenoceptors, using both [³H]CGP12177 and [¹²⁵I] ICYP ([¹²⁵I] 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 β₁-and β₂-adrenoceptors. A major metabolite of bopindolol, 18-502, had higher pK₁ and pA₂ 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 β₁-and β₂-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.
关键词：radioligand binding assay