Sustaining Effects of Bopindolol on Inhibitory Chronotropic Actions in Guinea Pig Atria

Abstract

The dissociating and/or residual inhibitory effects of bopindolol from β-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 β-antagonists rather than readily reversible β-AR antagonists. These effects may differ from those of propranolol and pindolol, although propranolol did not recover to control levels after washout with buffer.