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  • Title: Effect of an antiarrhythmic agent, carocainide, on action potentials of ventricular papillary muscle of the guinea-pig heart in vitro.
    Author: Muramoto J, Hotokebuchi N, Nishi K.
    Journal: Arch Int Pharmacodyn Ther; 1991; 312():27-38. PubMed ID: 1772338.
    Abstract:
    The effect of carocainide, a new benzofuran derivative showing an antiarrhythmic action in animal models, on transmembrane potentials was examined in isolated ventricular papillary muscles of guinea-pig, using a conventional microelectrode technique in vitro. Carocainide, at concentrations above 5 x 10(-6) M, induced a dose-dependent decrease of the maximum upstroke velocity at a stimulation frequency of 0.1 Hz, while the resting membrane potential, the amplitude and duration of action potential were not affected even at 5 x 10(-5) M. In the presence of carocainide, trains of stimuli higher than 1 Hz led to an exponential decline in maximum upstroke velocity to a new steady state level. This use-dependent block was augmented at the higher stimulation frequency as carocainide (5 x 10(-5) M) decreased the maximum upstroke velocity to 50-60% and to 40-50% of the initial level at 2 Hz and at 3 Hz, respectively. Carocainide (5 x 10(-5) M) at 1 Hz caused an appreciable shift (6-7 mV) of the curve at 50% of the maximum upstroke velocity (mid-point), bringing the membrane potential and the maximum upstroke velocity along the voltage axis in the hyperpolarizing direction. Our results indicate that carocainide has similar electrophysiological effects to those of other Class Ib antiarrhythmic drugs and that it can be characterized as a potent use-dependent sodium channel blocker.
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