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• W2019293991 abstract "1 Cardiac effects of Ro 22–9194 were examined in papillary muscles and single ventricular myocytes isolated from guinea-pigs and compared with those of moricizine. 2 In papillary muscles, both Ro 22–9194 (≥ μm) and moricizine (≥ μm) caused a significant dose-dependent decrease in the maximum upstroke velocity (V̇max) and a shortening of the action potential duration. 3 In the presence of either drug, trains of stimuli at rates ≥ 0.2 Hz led to an exponential decline in V̇max. This use-dependent block was enhanced at higher stimulation frequencies. A time constant (τR) for V̇max recovery from the use-dependent block was 9.3 s for Ro 22–9194 and 26.4 s for moricizine. 4 The curves relating membrane potential and V̇max in single myocytes were shifted by Ro 22–9194 (30 μm) or by moricizine (3 μm) in a hyperpolarizing direction by 8.4 mV and 8.0 mV respectively. 5 In myocytes treated with Ro 22–9194 (30 μm), a 10 ms conditioning clamp to 0 mV caused a significant decrease in V̇max of the subsequent test action potential; further prolongation of the clamp pulse duration resulted in a modest enhancement of the V̇max inhibition. In the presence of moricizine (3 μm), a similar conditioning clamp > 200 ms caused a significant V̇max reduction; the longer the clamp pulse duration, the greater the V̇max reduction. 6 Ro 22–9194 ≥ 30 μm caused a slight decrease of calcium inward current (ICa) of myocytes without affecting the delayed rectifier potassium current (IK). 7 These findings suggest that the primary electrophysiological effect of Ro 22–9194 as an antiarrhythmic agent is, like moricizine, a use- and voltage-dependent inhibition of sodium channels. From the onset and offset kinetics of the use-dependent block, Ro 22–9194 belongs to the intermediate kinetic Class I drugs, while moricizine is a slow kinetic drug. From the state-dependence of sodium channel block, Ro 22–9194 may belong to activated channel blockers, while moricizine belongs to inactivated channel blockers." @default.
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• W2019293991 date "1995-01-01" @default.
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• W2019293991 title "Electrophysiological effects of Ro 22-9194, a new antiarrhythmic agent, on guinea-pig ventricular cells" @default.
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• W2019293991 doi "https://doi.org/10.1111/j.1476-5381.1995.tb14900.x" @default.
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