| Abstract: | The effects of acebutolol (13-134 microM), pindolol (10-50 microM), oxprenolol (16-66 microM) and (+) and (-)-K?592 (39-193 microM) on action potentials were investigated in isolated guinea-pig papillary muscles. All the drugs reduced Vmax at 1 Hz, dose-dependently. The reduction was less prominent with prolongation of the interstimulus interval until there was virtually no reduction. The time course of recovery of Vmax during diastole was studied by assessing Vmax in premature responses at 0.1 Hz or in responses after interrupting driving stimuli at 1 Hz. Time constants of recovery thus estimated were 12 to 14 sec for acebutolol and pindolol, 3 to 6 sec for oxprenolol and 0.7 to 1 sec for (-)-K?592. The reduction of Vmax was rate dependent for all the drugs, and at 5 Hz, the order of potency was oxprenolol > pindolol > acebutolol congruent to (-)- and (+)-K?592. The most potent was alprenolol (3.5-17.5 microM), which we have already studied in detail. At 1 Hz or lower, the action potential duration was shortened by application of all the compounds mentioned except acebutolol, but tended to be longer than in control, at higher rates for all the drugs. We conclude that molecular bulkiness and dimension may be associated with the time constant of recovery, whereas the potency at high driving rates may be correlated roughly linearly with the lipid solubility of the agents. |
