Premium
Studies on the stereoisomers of β‐adrenoceptor antagonists in conscious A‐V blocked dogs
Author(s) -
Boucher Michel,
DuchêneMarullaz Pierre,
Moundanga Joseph Loufoua
Publication year - 1986
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1986.tb11127.x
Subject(s) - pindolol , metoprolol , propranolol , chronotropic , heart rate , bradycardia , isoprenaline , chemistry , medicine , pharmacology , stimulation , blood pressure
1 Atrial and ventricular chronotropic effects of the individual stereoisomers of propranolol, pindolol, metoprolol and penbutolol were studied in conscious dogs with chronic atrio‐ventricular (A‐ V) block. Ventricular β‐adrenoceptor blocking activity was assessed for all drugs against isoprenaline under the same experimental conditions. 2 At low doses, the stereoisomers of propranolol and penbutolol decreased atrial rate, whereas those of pindolol and metoprolol produced an increase. At higher doses, all drugs increased atrial rate. All drugs decreased ventricular rate dose‐dependently except (+)‐pindolol. 3 Relative ventricular β‐blocking potencies of the (‐)‐isomers of propranolol, pindolol, metoprolol and penbutolol were respectively 38, 21, >43 and 31 times higher than those of their corresponding (+)‐isomers. In addition, β‐blocking potencies of (‐)‐ and (+)‐pindolol were respectively 60 and 120 times higher, those of (‐)‐ and (+)‐penbutolol 7 and 8 times higher and those of (‐)‐ and (+)‐metoprolol 4 and >4 times weaker than those of (‐)‐ and (+)‐propranolol. 4 At comparable levels of ventricular β‐adrenoceptor blockade, (‐)‐pindolol and (‐)‐metoprolol were more potent in producing ventricular bradycardia than their respective (+)‐isomers, whereas (‐)‐ and (+)‐propranolol and (‐)‐ and (+)‐penbutolol were equiactive. In addition, regardless of which isomer was being studied, the order of ventricular bradycardiac potencies, at comparable levels of β‐adrenoceptor blockade, was metoprolol > propranolol > penbutolol > pindolol. 5 These results show that antagonism of β‐adrenoceptors in the ventricle is at least partly responsible for the ventricular bradycardiac effect produced by these drugs, but also that some other factor, apparently distinct from the membrane stabilizing activity, is involved, suggesting the existence of some other as yet unknown pharmacological property of the β‐adrenoceptor blocking drugs, especially evident in metoprolol. Finally, these results demonstrate that the intrinsic sympathomimetic activity exhibited by some of these drugs attenuate their bradycardiac effect.