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Beta-blocking potency and selectivity of bopindolol and its two metabolites for beta 1- and beta 2-adrenergic receptors as assessed by radioligand binding assay. 1991

N Sakuma, and H Tsuchihashi, and Y Hosohata, and H Akashi, and J Kinami, and T Nagatomo
Department of Pharmacology, Niigata College of Pharmacy, Japan.

Using a radioligand binding assay, we assessed the affinity and selectivity of the antagonistic effects of bopindolol (4-(benzoyloxy-3-tert-butylaminopropyl)-2-methylindole hydrogen-malonate) 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 beta 1- and beta 2-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 (beta 1-adrenoceptors) and for their antagonistic effects toward isolated tracheal relaxation (beta 2-adrenoceptors), using isoproterenol as an agonist. The data showed that bopindolol was more selective for beta 2-adrenoceptors than for beta 1-adrenoceptors and 5HT1B-receptors, but its two metabolites (18-502 and 20-785) did not have significant selectivity for beta 1- and beta 2-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 beta 1- and beta 2-adrenoceptors. A major metabolite of bopindolol, 18-502, had higher pKi and pA2 values for beta-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 beta 1- and beta 2-adrenoceptors is more effective than pharmacological experiments, and that there is a possibility that its two metabolites also contribute to the strong beta-blocking action of bopindolol.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D009119 Muscle Contraction A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. Inotropism,Muscular Contraction,Contraction, Muscle,Contraction, Muscular,Contractions, Muscle,Contractions, Muscular,Inotropisms,Muscle Contractions,Muscular Contractions
D009206 Myocardium The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow. Muscle, Cardiac,Muscle, Heart,Cardiac Muscle,Myocardia,Cardiac Muscles,Heart Muscle,Heart Muscles,Muscles, Cardiac,Muscles, Heart
D010869 Pindolol A moderately lipophilic beta blocker (ADRENERGIC BETA-ANTAGONISTS). It is non-cardioselective and has intrinsic sympathomimetic actions, but little membrane-stabilizing activity. (From Martindale, The Extra Pharmocopoeia, 30th ed, p638) Prindolol,LB-46,Visken,LB 46,LB46
D011412 Propanolamines AMINO ALCOHOLS containing the propanolamine (NH2CH2CHOHCH2) group and its derivatives. Aminopropanols
D011869 Radioligand Assay Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders). Protein-Binding Radioassay,Radioreceptor Assay,Assay, Radioligand,Assay, Radioreceptor,Assays, Radioligand,Assays, Radioreceptor,Protein Binding Radioassay,Protein-Binding Radioassays,Radioassay, Protein-Binding,Radioassays, Protein-Binding,Radioligand Assays,Radioreceptor Assays
D011943 Receptors, Adrenergic, beta One of two major pharmacologically defined classes of adrenergic receptors. The beta adrenergic receptors play an important role in regulating CARDIAC MUSCLE contraction, SMOOTH MUSCLE relaxation, and GLYCOGENOLYSIS. Adrenergic beta-Receptor,Adrenergic beta-Receptors,Receptors, beta-Adrenergic,beta Adrenergic Receptor,beta-Adrenergic Receptor,beta-Adrenergic Receptors,Receptor, Adrenergic, beta,Adrenergic Receptor, beta,Adrenergic beta Receptor,Adrenergic beta Receptors,Receptor, beta Adrenergic,Receptor, beta-Adrenergic,Receptors, beta Adrenergic,beta Adrenergic Receptors,beta-Receptor, Adrenergic,beta-Receptors, Adrenergic
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D006168 Guinea Pigs A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D006339 Heart Rate The number of times the HEART VENTRICLES contract per unit of time, usually per minute. Cardiac Rate,Chronotropism, Cardiac,Heart Rate Control,Heartbeat,Pulse Rate,Cardiac Chronotropy,Cardiac Chronotropism,Cardiac Rates,Chronotropy, Cardiac,Control, Heart Rate,Heart Rates,Heartbeats,Pulse Rates,Rate Control, Heart,Rate, Cardiac,Rate, Heart,Rate, Pulse

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