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 o ut with buffers on isoprenaline-induced chronotropic actions were determine d. The effects of this drug were com pared with those of its active metabol ite 18-502, propranolol, and pindolol. Our results are as follows: (1) Lowe r concentrations of bopindolol (10(-9) and 10(-8) mol/l) and the active met abolite 18-502 (10(-9) mol/l), propranolol (10(-8) and 10(-6) mol/l) and pi ndolol (10(-8) mol/l) produced rightward shifts of concentration-response c urves 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 cont rol levels at 180 min even after washout with buffers. In conclusion, bopin doiol and 18-502 may slowly dissociate and act as noncompetitive beta-antag onists rather than readily reversible beta-AR antagonists. These effects ma y differ from those of propranolol and pindolol, although propranolol did n ot recover to control levels after washout with buffer.