Beta-adrenoceptor blocking effects of two bopindolol metabolites in isolated guinea-pig atria.
The beta-adrenoceptor blocking effects of the bopindolol (Wandonorm, CAS 62658-63-3) metabolites 18-502 (indole-2,4- methylaminopropoxy(N-tert.butyl)-tartrate) and 20-785 (indole-2,4-carboxyaminopropoxy(N-tert.butyl] were studied in electrically stimulated guinea-pig left atria and in spontaneously beating guinea-pig atria in vitro. Both compounds shifted the concentration-response curve of isoprenaline to the right, but did not reduce the maximum effect of this drug. For compound 20-785, pA2 values of 7.44 (left atrium, inotropic effect) and 7.58 (right atrium, chronotropic effect) were calculated. The metabolite 18-502 had a much greater beta-adrenoceptor blocking potency, as judged from its pA2 values of 9.53 and 9.48, resp., and in the concentration of 10(-8) mol/l it caused a significant flattening of the concentration-response curve of isoprenaline. From these results, compound 20-785 can be classified as a competitive beta-adrenoceptor antagonist, while for higher concentrations of the metabolite 18-502 additional noncompetitive mechanisms of action cannot be excluded.
Institute of Pharmacology, Medical University of Lübeck, Fed. Rep. of Germany.
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D000319:Adrenergic beta-Antagonists / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010869:Pindolol / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D013268:Stimulation, Chemical
D000319:Adrenergic beta-Antagonists; C038186:4-(2-hydroxy-3-tert-butylaminopropoxy)-2-methylindole; C061293:4-(3-tert-butylamino-2-hydroxypropoxy)-2-carboxyindole; D010869:Pindolol; C036007:bopindolol; D007545:Isoproterenol