EFFECTS OF ACEBUTOLOL AND OTHER STRUCTURALLY RELATED BETA-ADRENERGIC BLOCKERS ON TRANSMEMBRANE ACTION-POTENTIAL IN GUINEA-PIG PAPILLARY-MUSCLES

  • 1 January 1980
    • journal article
    • research article
    • Vol. 215  (2) , 507-514
Abstract
The effects of acebutolol (13-134 .mu.M), pindolol (10-50 .mu.M), oxprenolol (16-66 .mu.M) and (+)- and .**GRAPHIC**. [1-(3-methylphenoxy)-2-hydroxy-3-isopropylamino propane] (39-193 .mu.M) on action potentials were investigated in isolated guinea pig papillary muscles. All the drugs reduced .ovrhdot.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 .ovrhdot.Vmax during diastole was studied by assessing .ovrhdot.Vmax in premature responses at 0.1 Hz or in responses after interrupting driving stimuli at 1 Hz. Time constants of recovery estimated were 12-14 s for acebutolol and pindolol, 3-6 s for oxprenolol and 0.7-1 s for .**GRAPHIC**. The reduction of .ovrhdot.Vmax was rate dependent for all the drugs, and at 5 Hz, the order of potency was oxprenolol > pindolol > acebutolol .simeq. (-)- and .**GRAPHIC**. The most potent was alprenolol (3.5-17.5 .mu.M), which was 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. Molecular bulkiness and dimension may be associated with the time constant of recovery, but the potency at high driving rates may be correlated roughly linearly with the lipid solubility of the agents.

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