Bopindolol: A Slowly Dissociating Antagonist from the β-Adrenoceptors in Guinea Pig Atria

Abstract

The dissociating and/or residual inhibitory effects of bopindolol from β-adrenoceptors of atria strips pretreated with this drug which was then washed out with buffers on the responses to isoprenaline were determined and compared with those of propranolol, pindolol, atenolol, and the two active metabolites of bopindolol: 18-502 and 20-785. Low concentrations of bopindolol (10^–9 to 10^–8 mol/l) and the active metabolite 18-502 (10^–9 mol/l) produced rightward shifts of the concentration-response curves. On the other hand, high concentrations of bopindolol (10^–7 mol/l) and metabolite 18-502 (10^–8 and 10^–7 mol/l) produced a reduced maximum response by isoprenaline, suggesting that these nonparallel rightward shifts have pD₂ values of 7.57 (bopindolol) and 7.67 (18-502), respectively, at 0 min after washout with buffers. Pindolol (10^–7 mol/l) and propranolol (10^–7 and 10^–8 mol/l) also produced a rightward shift of isoprenaline response curves, and these concentration-response curves in guinea pig atria strips pretreated with pindolol (10^–7 mol/l) and propranolol (10^–6 mol/l) recovered to control levels. Neither of these drugs, however, reduced the maximum response by isoprenaline. A high concentration (10^–5 mol/l) of atenolol was required for a rightward shift of the isoprenaline concentration-response curve, and this drug also did not reduce the maximum response. Thus, we conclude that bopindolol and metabolite 18-502 slowly dissociate and act as noncompetitive β-antagonists rather than easily reversible β-adrenoceptor antagonists.