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  • Title: Frequency- and voltage-dependent effects of aprindine on the upstroke velocity of action potential in guinea pig ventricular muscles.
    Author: Toyama J, Kamiya K, Kodama I, Yamada K.
    Journal: J Cardiovasc Pharmacol; 1987 Feb; 9(2):165-72. PubMed ID: 2435994.
    Abstract:
    The effects of aprindine on transmembrane action potentials were examined in isolated papillary muscles of guinea pig. Aprindine (10(-6)-10(-5) M) caused a dose-dependent decrease in the Vmax of the action potential without affecting the resting potential. In the presence of aprindine, trains of stimuli at rates greater than 0.1 Hz led to an exponential decline in Vmax. This use-dependent block was enhanced at the higher stimulation frequency. The time constant for the recovery of Vmax from the use-dependent block (offset) was 6.2-7.8 s. In depolarized papillary muscles with high [K+]o, the inhibitory action of aprindine on Vmax 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. The curves relating membrane potential and Vmax were shifted by 7.3 mV with aprindine at 3 X 10(-6) M in the direction of more negative potentials. These findings suggest that aprindine has quinidinelike use-dependent inhibitory action on the fast sodium channels of cardiac muscles. This use-dependency and its greater inhibition of Vmax in depolarized muscles through the augmentation of tonic block may play a major role for the drug action to prevent ventricular arrhythmias.
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