Effects of dimethylpropranolol (UM-272) on the electrophysiological properties of guinea-pig ventricular muscles

I Kodama, N Kondo, S Shibata and K Yamada

The effects of dimethylpropranolol (UM-272) on transmembrane action potentials were examined in isolated right ventricular papillary muscles of the guinea pig. UM-272 (10(-5) to 3 X 10(-4) M) caused a dose-dependent decrease in the Vmax of the action potential. At 3 X 10(- 4) M, a slight decrease in the amplitude of action potential was also observed. The resting potential and the action potential duration were not affected by the drug. In the presence of UM-272, trains of stimuli at rates higher than 0.1 Hz led to an exponential decline in Vmax (onset rate, 0.13-0.28 per action potential) to a new plateau level. This use-dependent block was augmented at the higher stimulation frequency. The time constant for the recovery of Vmax from the use- dependent block (offset) was 7.1 to 7.3 sec. In depolarized papillary muscles with 8 or 10 Mm [K+]0, the inhibitory action of UM-272 on Vmax of the first action potential after a long quiescent period (tonic block) was augmented markedly, but the rates of onset and offset of the use-dependent block were similar to those in normally polarized preparations under 5 mM [K+]0. The curves relating membrane potential and Vmax in preparations stimulated infrequently were shifted by 7.2 mV with UM-272 at 10(-4) M in the direction of more negative potentials. These findings suggest that UM-272 has kinetically similar use- dependent inhibitory action of the fast sodium channels of cardiac muscles as other Class Ia antiarrhythmic drugs like quinidine or procainamide.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 234, Issue 2, pp. 507-514, 08/01/1985
Copyright © 1985 by American Society for Pharmacology and Experimental Therapeutics