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The GABA derivative TZ-50-2 exerted pronounced antiarrhythmic effects on a variety of arrhythmias (atrial, ventricular, and mixed). The drug was superior (or at least comparable) to quinidine, procainamide, lidocaine, verapamil, bonnecor, and other reference drugs in antiarrhythmic activity and therapeutic range, and showed no cardiotoxicity. The antiarrhythmic effects of TZ-50-2 were due to modulation of calcium and sodium channels. Key Words: GABA; cardiac arrhythmiasAntiarrhythmic potency of local anesthetics and anticonvulsants with similar mechanisms of action attracts now considerable attention [10]. The novel GABA derivative hemisuccinate 4-oxi-3-benzylamino-N-benzylbutan amide (laboratory code TZ-50-2) exhibits both local anesthetic [9] and anticonvulsant properties [6]. This work was aimed at investigation of antiarrhythmic activity (AA) of TZ-50-2 on different models of atrial, ventricular, and mixed arrhythmias. MATERIALS AND METHODSExperiments were carried out on 446 outbred male albino rats (175-220 g), 48 mongrel rabbits (2.8-3.6 kg), 98 cats (2.6-4.2 kg), and 31 dogs (14-22 kg) of both sexes, as well as on isolated atria (trabecular and auricular preparations) of frogs (n=36) and guinea pigs (n=20).Toxicity of TZ-50-2 and reference drugs (mean lethal dose, LDs0 ) was determined in experiments on rats with single intravenous injection followed by 48-h monitoring [3,7].The ECG (R, RR, QT, PQ, QRS) were recorded in standard lead II with EKIT-04 electrocardiograph in experiments on dogs under pentobarbital anesthesia (40 mg/kg, intrapleurally) with drug administration by biological titration (1 mg/kg/ml) until cardiac arrest. Drug effects on the myocardial reli;actory period were studied on isolated auricles of guinea pig heart [8]. The effects on action potentials and transmembrane ionic currents were studied on isolated atrial trabeculas from the heart of Rana ridibunda [ 12].The antiarrhythmic efficacy of the drugs was evaluated by comparing their potencies (mean effective doses, EDs0) and antiarrhythmic indices (LDs0/ED~0) characterizing the therapeutic window (TW) [3].The data were analyzed statistically [3]. RESULTSIntravenous inl~asion of TZ-50-2 had no effect on the ECG indices in the anesthetized dogs up to a total dose of 50 mg/kg (reached over 50 min). Further infusion (up to 60-120 mg/kg) caused respiration arrest

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