Effect of befol on the electric threshold of ventricular fibrillation

Abstract

Befol (20 mg/kg) rises electric threshold of ventricular fibrillation in cats. This effect is most pronounced in ischemized myocardium. It is shown that not only tricyclic but also monocyclic antidepressants exhibit antifibrillatory activity. Key Words: befol; ventricular fibrillation; ischemia, treatmentThe antidepressant befol, 4-chlorine-N-(3-morpholynopropyl)-benzamide hydrochloride, is a reversible inhibitor of monoamine oxidase (type A by serotonin substrate) synthesized at the Institute of Pharmacology (Russian Academy of Medical Sciences) [1,4]. Clinical trials showed that this drug possesses both antidepressant and antiarrhythmic activities [3,6].Therefore, it was interesting to assess the antifibrillatory activity (AFA) of befol, which is a monocyclic antidepressant, in animal experiments, bearing in mind the finding that some tricyclic antidepressants (metapramine, imipramine, and momyphenzin) exhibit AFA in acute regional myocardial ischemia (ARMI) [8][9][10]12]. MATERIALS AND METHODSExperiments were performed on anesthetized (sodium pentobarbital, 40 mg/kg, intravenously) cats (body weight 2.3-3.0 kg) of both sexes. Catheters were inserted in the right femoral vein for befol infusion and in the left femoral artery for measuring arterial pressure with an Elema-Simens electromanometer. Silver bipolar electrodes were sutured to the right ventricle of the heart after thoraco-and pericardiotomy. After a 10-min stabilization period, electric Department of Pharmacology, Kuban State Medical Academy, Krasnodar; Laboratory of Circulatory Pharmacology, Institute of Pharmacology, Russian Academy of Medical Sciences, Moscow threshold of ventricular fibrillation (ETVF) was determined by scanning the electrically vulnerable period of cardiac cycle (ascending portion of T wave) with a series of 20 rectangular direct current pulses of increasing intensity (pulse duration 4 msec, frequency 50 pulses/sec) until the appearance of ventricular fibrillation. Electrocardiogram (lead II) was recorded with an EKChT-02 electrocardiograph with a simultaneous record in an Attack-359 analyzer (Nihon Kohden). Direct electric countershock was delivered from a DI-3 apparatus. Acute regional myocardial ischemia was produced by occlusion of the descending branch of the left coronary artery between its upper and middle thirds. Befol was slowly infused using a Syringer Pump 355 (Sage Instruments). Three series of experiments (5 cats in each) were performed. In the first series, the effect of befol (5, 10, 15, and 20 mg/kg) on ETVF was studied in intact cats. In the second series, the effect of ARMI on ETVF was examined. In the third series, the effect of befol (20 mg/kg) on ETVF was assessed in cats with ARMI. The results were statistically processed using conventional methods [5]. RESULTSAt 5 and 10 mg/kg befol had no appreciable effect of ETVF (Table 1). A tendency toward an increase in ETVF was observed at 15 mg/kg, and a statistically significant rise of ETVF by 2.2 times was recorded

Effect of befol and sufan on neurogenic atrial fibrillation

“…The data were processed statistically [3], the mean and its deviation for each parameter and significance of differences were determined.…”

“…Befol is superior to quinidine, ethmozine, and bonnecor in antiarrhythmic activity (in isotoxie doses) [3,15]. Antiarrhythmic effects of verapamil and bonnecor in delayed ventricular CRD can be potentiated by befol+ verapamil and by befol+bonnecor [15].…”

Coronarotropic properties of cyclic GABA derivative TZ-146

“…When tested in vivo, this preparation increased the indices of phasic coronary blood flow in dogs, surpassing the effects of reactive hyperemia, which characterizes the dilatory capacity of coronary vessels. Pharmacological analysis and experiments with bilateral vagotomy in cats and dogs suggest that coronarotropic effects of TZ-146 can result from activation of adenylate cyclase and accumulation of cAMP.Key Words: GABA; coronary blood flow It has been shown that TZ-146 (cyclic GABA derivative, a structural analog of piracetam) prevents disturbances in both systemic and cardiac hemodynamics by enhancing coronary blood flow volume velocity (VVCF) in ischemized myocardium in vivo [2]. It is of interest, therefore, to study coronodilatory properties of TZ-146 in experiments on isolated hearts, its effect on phase coronary blood flow (CBF), the mechanisms of coronodilatory effects.…”

Antiarrhythmic activity of befol, suphan, mexidol, and T3-146 in combination with some antiarrhythmics

“…Recently, some drugs, such as antidepressant befol (4-chlorine-3-morpholinopropyl-benzamide hydrochloride) [3], nonglycoside cardiotonic suphan (dipotassium salt of N-succinyl-dl-tryptophan) [5], mexidol, a synthetic antioxidant from the group of derivatives of 3-oxypyridine (succinate-containing analogue of emoxypinum) [1], as well as substance T3-146, a cyclic derivative of ,/-aminobutyric acid (malate-containing analogue of pyracetam) [4] exhibit antiarrhythmic and anti fibrillation activities, and produce antianginal and antihypoxic effects. In addition, they could stabilize the hemodynamic parameters in acute myocardial ischemia.…”