Beta-blocking Potency and Selectivity of Bopindolol and Its Two Metabolites for β1-and β2-Adrenergic Receptors as Assessed by Radioligand Binding Assay

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-...

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Veröffentlicht in:Journal of Pharmacobio-Dynamics 1991, Vol.14(5), pp.250-255
Hauptverfasser: SAKUMA, Noriko, TSUCHIHASHI, Hiroshi, HOSOHATA, Yoshiaki, AKASHI, Hirofumi, KINAMI, Junji, NAGATOMO, Takafumi
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container_end_page 255
container_issue 5
container_start_page 250
container_title Journal of Pharmacobio-Dynamics
container_volume 14
creator SAKUMA, Noriko
TSUCHIHASHI, Hiroshi
HOSOHATA, Yoshiaki
AKASHI, Hirofumi
KINAMI, Junji
NAGATOMO, Takafumi
description 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 5HT1B-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 5HT1B-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 5HT1B-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.
doi_str_mv 10.1248/bpb1978.14.250
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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 5HT1B-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 5HT1B-receptors than those of bopindolol and 20-785. 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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 5HT1B-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 5HT1B-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.</description><subject>Antihypertensive agents</subject><subject>Biological and medical sciences</subject><subject>Cardiovascular system</subject><subject>Medical sciences</subject><subject>Pharmacology. 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Drug treatments</topic><topic>radioligand binding assay</topic><toplevel>online_resources</toplevel><creatorcontrib>SAKUMA, Noriko</creatorcontrib><creatorcontrib>TSUCHIHASHI, Hiroshi</creatorcontrib><creatorcontrib>HOSOHATA, Yoshiaki</creatorcontrib><creatorcontrib>AKASHI, Hirofumi</creatorcontrib><creatorcontrib>KINAMI, Junji</creatorcontrib><creatorcontrib>NAGATOMO, Takafumi</creatorcontrib><collection>Pascal-Francis</collection><jtitle>Journal of Pharmacobio-Dynamics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>SAKUMA, Noriko</au><au>TSUCHIHASHI, Hiroshi</au><au>HOSOHATA, Yoshiaki</au><au>AKASHI, Hirofumi</au><au>KINAMI, Junji</au><au>NAGATOMO, Takafumi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Beta-blocking Potency and Selectivity of Bopindolol and Its Two Metabolites for β1-and β2-Adrenergic Receptors as Assessed by Radioligand Binding Assay</atitle><jtitle>Journal of Pharmacobio-Dynamics</jtitle><addtitle>Journal of Pharmacobio-Dynamics</addtitle><date>1991</date><risdate>1991</risdate><volume>14</volume><issue>5</issue><spage>250</spage><epage>255</epage><pages>250-255</pages><issn>0386-846X</issn><eissn>1881-1353</eissn><coden>JOPHDQ</coden><abstract>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 5HT1B-receptors in rat brain and heart. 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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.</abstract><cop>Tokyo</cop><pub>The Pharmaceutical Society of Japan</pub><doi>10.1248/bpb1978.14.250</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record>
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source Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; J-STAGE (Japan Science & Technology Information Aggregator, Electronic) Freely Available Titles - Japanese
subjects Antihypertensive agents
Biological and medical sciences
Cardiovascular system
Medical sciences
Pharmacology. Drug treatments
radioligand binding assay
title 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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