Ethacizin: a new efficacious Soviet antiarrhythmic drug of the phenothiazine group.

Ethacizin, a new Soviet antiarrhythmic agent of the phenothiazine group, was tested on 82 patients with ventricular rhythm disturbances. Antiarrhythmic effects of the drug were assessed by means of ambulatory ECG monitoring. The investigation protocol included acute drug testing with 50 mg, 100 mg, and 150 mg, and short-term maintenance therapy with 150 to 300 mg/24 hours of ethacizin (mean 183 +/- 46 mg/24 hours) for 3 to 14 days (mean 7 +/- 3 days). Ethacizin reduced the total number of ventricular premature beats (VPBs) from 17,263/24 hours (on placebo) to 3458/24 hours (p less than 0.001) and suppressed couplets and ventricular tachycardia (VT) runs by 90% in 94% and 96% of patients, respectively. Maximum blood plasma concentration of ethacizin was observed in 110 to 120 minutes and accounted for 300 to 447 ng/ml (mean 354 +/- 77 ng/ml), with a minimum therapeutic drug plasma concentration ranging from 29 to 101 ng/ml (mean 73 +/- 27 ng/ml). There was a significant increase in PQ and QRS intervals with ethacizin. Ethacizin was well tolerated. Thus ethacizin had high antiarrhythmic efficacy in patients with VPBs and no significant side effects.

Ethmozin. I. Effects of intravenous drug administration on paroxysmal supraventricular tachycardia in the ventricular preexcitation syndrome.

Electrophysiologic effects of intravenous ethmozin (1.5 to 2 mg/kg) were evaluated in 16 patients (10 with Wolff-Parkinson-White [WPW] syndrome and six with concealed accessory pathway [AP]) with ventricular preexcitation syndrome. Ethmozin terminated induced supraventricular tachycardia (SVT) in 9 of 14 patients and atrial flutter with anterograde conduction 2: 1 over AP in one patient. The drug prevented induction of sustained SVT in 8 of 14 patients (four with WPW syndrome and four with concealed AP). The drug significantly lengthened the cycle length of induced SVT in WPW syndrome (381 +/- 24 to 421 +/- 27 msec) and in concealed AP (313 +/- 19 to 343 +/- 15 msec), mainly because of prolongation of the ventriculoatrial (VA) interval; the drug increased SVT atrial zone in WPW syndrome and removed or decreased it in patients with concealed AP. The drug abolished anterograde (6 of 10 patients) and retrograde (3 of 16 patients) conduction over AP, and/or increased anterograde and retrograde refractoriness of AP in all patients. Ethmozin significantly lengthened the following: PA (27 +/- 2 to 40 +/- 3 msec), AH (92.6 +/- 6 to 107 +/- 8 msec), and PR intervals (175 +/- 9 to 202 +/- 15 msec), and refractoriness of VA conduction systems. The refractoriness of atrioventricular node, HV, QRS, and QT intervals and the spontaneous sinus cycle length did not change significantly. Thus intravenous ethmozin terminated induced SVT and prevented the induction of sustained SVT in most patients with preexcitation syndrome due to a suppressive effect of the drug on AP.

Ethmozin. II. Effects of intravenous drug administration on atrioventricular nodal reentrant tachycardia.

Electrophysiologic studies were performed in 11 patients with atrioventricular (AV) nodal reentrant tachycardia (SVT) before and after intravenous administration of 1.5 to 2 mg/kg ethmozin. Initially, 9 of 11 patients had induction of sustained SVT, and two remaining patients had nonsustained SVT and atrial echoes, respectively. Ethmozin terminated induced SVT in six of nine patients. In six of nine patients ethmozin prevented the development of sustained SVT, indicating that ethmozin depressed retrograde fast pathway AV nodal conduction. In four of these patients atrial echoes were abolished. In the two remaining cases ethmozin prevented the induction of nonsustained SVT. In only three of these nine patients was sustained SVT induced. Anterograde fast and slow pathway properties did not significantly change with ethmozin administration. Effective refractory period (ERP) of the ventriculoatrial (VA) conduction system and ventricular paced cycle length producing VA block was 305 +/- 40 (mean +/- SEM) and 347 +/- 38 msec before and 424 +/- 105 and 475 +/- 71 msec after ethmozin administration, respectively (p less than 0.01, n = 8), suggesting depression of retrograde pathway with ethmozin administration. Ethmozin significantly (p less than 0.05) lengthened PA, AH, HV, and PR intervals (36 +/- 11 to 45 +/- 14 msec, 84 +/- 21 to 93 +/- 17 msec, 42 +/- 8 to 50 +/- 7 msec, and 163 +/- 23 to 190 +/- 31 msec, respectively). No significant change was observed in sinus rate, QRS and QT intervals, or ERP of atrium and ventricle. Thus, a single intravenous dose of ethmozin terminated induced SVT and prevented induction of sustained SVT in most patients, reflecting depression of retrograde fast pathway conduction.