Rosenshtraukh L V, Anyukhovsky E P, Nesterenko V V, Undrovinas A I, Shugushev K Kh, Portnoy V F, Burnashev N A
Laboratory of Electrophysiology of the Heart, All-Union Cardiology Research Center, Moscow, USSR.
Am J Cardiol. 1987 Oct 16;60(11):27F-34F. doi: 10.1016/0002-9149(87)90717-x.
Moricizine HCl, a phenothiazine derivative, is a new antiarrhythmic drug that has quinidine-like effects on the myocardium. Moricizine HCl, 1 X 10(-7) g/ml, significantly decreases Vmax of the transmembrane action potential of canine Purkinje fibers and reduces the duration of the action potential at 50% and 90% of repolarization, whereas resting potential is unchanged. The drug decreases the fast inward sodium current (lNa), as measured by the double sucrose gap technique in frog atrium trabeculae; the processes of activation, inactivation and reactivation of current did not change even when a high concentration of drug (5 X 10(-6) g/ml) was used. At the same dose, the slow inward calcium current (lCa) increased, but the total outward current did not change. Using the patch-clamp technique, it was shown that moricizine HCl, 1 X 10(-4) g/ml, did not alter single-channel conductance, but essentially decreased the mean open tonic and open-state probability of potassium channels either at positive or negative holding potentials. lNa measured in a single myocyte preparation decreased faster when drug was administered in the external bath compared with intracellular injection. Moricizine HCl action on lNa of the single cell and on Vmax of the action potential is frequency dependent. When lNa was recorded directly, there was a cumulative effect of drug. Similar to other quinidine-like agents, moricizine HCl enhanced arrhythmogenicity within the first few minutes after coronary artery occlusion, but prevented arrhythmias 24 hours after acute myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)
