Characterization of the antagonism with metoprolol, ICI 147,798, pindolol, mepindolol and bopindolol on the responses of the rat left atria to isoprenaline.
The aim of the study was to determine whether the antagonism with pindolol, mepindolol and bopindolol at the beta 1-adrenoceptor of the rat left atria, a tissue with plenty of spare beta 1-adrenoceptors for isoprenaline maximum responses, was readily reversible or not. The effects of these drugs were compared to those of metoprolol, a readily reversible, and of ICI 147,798, an irreversible beta-adrenoceptor antagonist. Metoprolol at 10(-7) and 10(-6) M, ICI 147,798, pindolol, bopindolol (all at 10(-8) and 10(-7) M) and mepindolol at 10(-9) and 10(-8) M inhibited the cardiac stimulation responses to a small extent, which is indicative of membrane stabilizing activity, and also caused surmountable antagonism of isoprenaline responses. The inhibitory effects on the isoprenaline responses of metoprolol and pindolol were readily reversible, that of mepindolol was slowly reversible and those of ICI 147,798 and bopindolol were not reversed in 3 h. The inhibitory effects on isoprenaline responses of metoprolol at 10(-6) M, pindolol and bopindolol at 10(-7) M and mepindolol at 10(-8) M were at equilibrium, which is indicative of reversible, whereas the inhibitory effects of ICI 147,798 were increased, which is indicative of irreversible antagonism, when the beta-blocker treatment time was increased from 1 to 2 h. We conclude that the antagonism with pindolol at the beta 1-adrenoceptors of the rat left atria is readily reversible, that of mepindolol is slowly reversible and that of bopindolol is very slowly reversible.
Department of Pharmacology, School of Medicine, University of Auckland, New Zealand.
A J
AJ
Surman
S A
SA
Doggrell
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D006321:Heart / Q000187:drug effects*; D007545:Isoproterenol / Q000037:antagonists & inhibitors*; D008297:Male; D008790:Metoprolol / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects; D010869:Pindolol / Q000031:analogs & derivatives / Q000494:pharmacology; D011719:Pyrazines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
D000319:Adrenergic beta-Antagonists; D011719:Pyrazines; D011943:Receptors, Adrenergic, beta; C015340:mepindolol; C053707:ICI 147798; D010869:Pindolol; D008790:Metoprolol; D007545:Isoproterenol