Sustaining effects of bopindolol on inhibitory chronotropic actions in guinea pig atria.
The dissociating and/or residual inhibitory effects of bopindolol from beta-adrenoceptors (ARs) of atria strips pretreated with this drug and washed out with buffers on isoprenaline-induced chronotropic actions were determined. The effects of this drug were compared with those of its active metabolite 18-502, propranolol, and pindolol. Our results are as follows: (1) Lower concentrations of bopindolol (10(-9) and 10(-8) mol/l) and the active metabolite 18-502 (10(-9) mol/l), propranolol (10(-8) and 10(-6) mol/l) and pindolol (10(-8) mol/l) produced rightward shifts of concentration-response curves of isoprenaline. (2) Higher concentrations of bopindolol (10(-7) mol/l) and 18-502 (10(-8) and 10(-7) mol/l) produced a reduced maximum response by isoprenaline. (3) Bopindolol (10(-9)-10(-7) mol/l), 18-502 (10(-9)-10(-7) mol/l) and propranolol (10(-7) and 10(-6) mol/l) did not recover to control levels at 180 min even after washout with buffers. In conclusion, bopindolol and 18-502 may slowly dissociate and act as noncompetitive beta-antagonists rather than readily reversible beta-AR antagonists. These effects may differ from those of propranolol and pindolol, although propranolol did not recover to control levels after washout with buffer.
Hattori
K
K
Department of Pharmacology, Fukui Medical School, Matsuoka, Fukui, Japan.
Suzuki
J
J
Hosohata
Y
Y
Ohnuki
T
T
Nakamura
T
T
Watanabe
K
K
Muramatsu
I
I
Nagatomo
T
T
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / 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* / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011433:Propranolol; D010869:Pindolol; C036007:bopindolol; D007545:Isoproterenol