[ANTIARRHYTHMIC EFFECTS OF 2-ETHYL-6-METHYL-3-HYDROXYPYRIDINE HEMISUCCINATE IN COMPARISON TO MEXIDOL.].

Based on the results of experiments on nonlinear white awake male rats it is established that 2-ethyl-6-methyl-3-hydroxypyridine hemisuccinate and mexidol exhibit a pronounced antiarrhythmic (antifibrillatory) activity on the calcium chloride arrhythmia model. The maximum effect was observed for hemisuccinate 2-ethyl-6-methyl-3-hydroxypyridine. This substaned; unlike mexidol, also showed high activity on the model of aconitine arrhythmia, which is typical of class I antiarrhytmics.

[GABAergic mechanism of cerebrovascular effect of the NMDA receptor antagonist MK-801].

NMDA receptor antagonist MK-801 (dizocilpine) increases the local blood flow in the cerebral cortex in rats under transient global ischemia (TGI) conditions to a greater degree than in intact animals. The GABA receptor blocker bicuculline in most experiments eliminates or reduces the MK-801 induced increase in the blood flow after TGI, which is indicative of the participation of GABAergic mechanism of cerebrovascular tone control in the observed MK-801 activity.

[Search for new drugs with antiarrhythmic properties among derivatives of adamant-2-ylamides of alkylamidocarbonic acids].

The experiments on white outbred awaken male rats have shown that derivatives of adamant-2-ylamides of alkylamidocarbonic acids exhibit prominent antiarrhythmic (antifibrillatory) effect on the model of calcium chloride arrhythmia. The most pronounced effect was demonstrated by N-[2(adamant-2-yl)aminocarbonylmethyl]-N'-[3-(diethylamino)propyl]-4-nitrobenzamide. This compound was also active on the model of aconitine arrhythmia, which is characteristic of class-I antiarrhythmic agents.

[Adamantane derivate enhances cerebral blood flow under conditions of ischemic brain damage].

Experiments have shown that adamantane derivate - 5-hydroxyadamantan-2-on (100 mg/kg, i.v.) enhances the local blood flow in the cerebral cortex of rats under global transient brain ischemia conditions, while not influencing the brain blood flow in intact rats.

[Cerebrovascular and antiserotoninergic activity of the combination of tropoxin and mexidol].

The results of experiments on narcotized rats showed that tropoxin substantially reduces the constrictor reactions of cerebral blood vessels to meta-chlorophenylpiperazine, while not increasing the blood flow in the carotid system of either intact rats or animals with model ischemic damage of brain. In contrast, mexidol increases the cerebral blood flow in rats under conditions of global transient ischemia of brain. A combination of tropoxin and mexidol retains both the anti-serotoninergic activity of tropoxin and the vasodilating effect of mexidol.

[Antiarrhythmic properties of afobazole and other 2-mercaptobensimidazole derivatives].

Experiments on conscious male rats have shown that, under conditions of the aconitine-induced arrhythmia model, afobazole and other 2-mercaptobensimidazole derivatives exhibit antiarrhythmic effect, i.e. possess properties of rapid Na+ channel antagonists.

[Afobazole effect on cerebral circulation under hemorrhagic stroke model conditions].

Narcotized rats under hemorrhagic stroke model conditions exhibit a significant decrease in the cerebral flow in the region of contralateral cerebral hemisphere symmetric to the zone of lesion. Under these conditions, afobazole produced a significant increase in the local circulation in cerebral cortex, which was violated by hemorrhagic stroke. The cerebrovascular effect of afobazole was not manifested in cases of hemorrhagic stroke on the background of GABA receptor blocking by bicuculline.

[Effects of afobazole on the stress protein HSP70 level in the brain tissue of rats with global transient ischemia].

Experiments in anesthetized rats showed that global transient brain ischemia caused a significant decrease in cerebral blood flow in rat cerebral cortex and reduced the stress protein HSP70 level in striatum. Afobazole administration restored the cerebral blood supply disturbed by ischemia and increased the stress protein HSP70 synthesis in striatum.

Antiarrhythmic properties of estrogens.

Estrone, estriol, and estradiol valerate exhibited antiarrhythmic activity in rats with aconitine-induced arrhythmia. Estrone was most effective in this respect.

[Anti-arrhythmia activity of estradiol valerate and estradiol nitrate].

Estradiol valerate and estradiol nitrate exhibit significant antiarrhythmic activity of on the aconitine arrhythmia model in rats. In both cases, the maximum effect was observed in a dose of 0.5 mg/kg.

[The effect of novel class III anti-arrhythmia agents cardiocyclide and nibentan during activation of cardiac beta-adrenoreceptors].

The effect of cardiocyclide and nibentan--class III antiarrhythmics--on the heart rate frequencies (HRF) and the EEG intervals (PQ, QRS, QT, and QTc) was experimentally studied on narcotized rats under conditions of the isoproterenol-induced activation of beta-adrenergic structures. It was established that cardiocyclide retains properties of the class III drug, as manifested by decreased HRF and increased QT duration in the absence of changes in the conductivity. In contrast, the activity of nibentan was decreased on the background of activation of the sympathetic system.

[The anti-arrhythmia activity of new dicyclohexylamide derivatives of N-substituted alpha-aminocarboxylic acids].

Experiments on arrhythmia models showed a high antiarrhythmic activity of new derivatives of dicyclohexylamides of N-replaced alpha-aminocarbonic acids. The new compounds surpassed in intensity and duration of the antiarrhythmic effect the standard agents with classes I and III antiarrhythmic activity. In doing so they raise myocardial electrical stability and prevent sudden development of ventricular fibrillation.

[A new class-III antiarrhythmic preparation among the dicyclohexylamides of aminocarboxylic acids].

The Institute of Pharmacology, Academy of Medical Sciences, jointly with AWD (Germany) has synthesized and tested a novel class III antiarrhythmic coded AWD-160-275, a derivative of dicyclohexylamides of aminocarboxylic acids. The compound was shown to prolong cardiac repolarization, to increase atrial and ventricular refractory periods, to decrease sinus nodal automatism, and to unchange intraventricular conduction. The compound proved to be superior to the reference drugs in the rate and duration of antiarrhythmic and antifibrillatory action.

[The pharmacology of the new combined anti-arrhythmia preparation metatsizin].

The combined antiarrhythmic effect of ethmosin and ethacisin in various dose ratios was studied in conscious dogs with two-stage ligation of the coronary artery (after Harris). A 6:1 ratio was found to be optimal for manifestation of the antiarrhythmic effect. In such a ratio of the doses the antiarrhythmic effect of a combination of ethmosin and ethacisin is essentially higher than the activity of each component.

[Anti-arrhythmic properties of specific bradycardic agents from the group of 2-mercaptobenzimidazole derivatives].

It was shown in experiments on aconitine, calcium chloride, and epinephrine models of heart rhythm disorders that derivatives of 2-mercaptobenzimidasole possessing the properties of specific bradycardiac agents coded as SM-251, SM-266, and SM-345 cause a marked antiarrhythmic effect. SM-266 and SM-345 reduce considerably the number of ventricular fibrillations and the life-hazardous arrhythmia occurring during 7-min occlusion and subsequent reperfusion of the coronary artery in anesthetized rats. The agents under study reduced the ectopic heart rate in Harris' conscious dogs.

[A comparative study of the antiarrhythmic action of bonnecor and the mesidide derivatives of alpha-azacycloalkane carboxylic acids].

The antiarrhythmic properties of the dibenzazepine derivative bonnecor and derivatives of mesidides of alpha-azacycloalkanocarboxylic acids were studied in various experimental arrhythmia models. The comparative study revealed different antiarrhythmic effects in different arrhythmia models. Bonnecor was found to have a higher antiarrhythmic activity in most arrhythmic models.

[The anti-arrhythmic activity of the arylamides of alpha-hexamethyleneiminocarboxylic acids].

A high antiarrhythmic activity of arylamides of alpha-hexamethyleniminocarbonic acids was found on different experimental models of arrhythmias. It was shown that the lengthening of the carbonic chain in carbonic acids (R) as well as the change from ortho-toluidides to xylidides or mesidides in the aromatic fragment of the molecule increased the antiarrhythmic activity of the studied compounds, their toxicity also increased. The choice of compounds with optimal properties is determined by the combination of all investigated factors: intensity and duration and also the specific features of the spectrum of the antiarrhythmic effect, toxicity and therapeutic range.

[The relationship between the chemical structure and the antiarrhythmic action of ethacizine and its analogs].

The relationship between the chemical structure and the antiarrhythmic activity of phenothiazine derivatives--ethacizine and its analogues--was estimated quantitatively by the value of the antiarrhythmic effect on aconitine model in conscious rats. The lengthening of the side chain of nitrogen atom in position 10 of phenothiazine cycle by one methylene group as well as the substitution of demethylamine radical for diethylamine one increased the antiarrhythmic activity; the toxicity of the compound being also increased. Ethacizine was found to possess the highest antiarrhythmic activity and the greatest antiarrhythmic index.

[Bonnecor--a new anti-arrhythmia preparation].

The antiarrhythmic properties of a new drug bonnecor being a derivative of dibenzazepine were studied on different models of arrhythmias. Bonnecor proved to be effective in the treatment of both atrial and ventricular arrhythmias of various genesis except rhythm disorders induced by ouabain intoxication. The drug was shown to exert a pronounced antifibrillatory effect and to increase the electrical stability of the intact and ischemic myocardium.

[Characteristics of the protective action of ethacizin on the ischemic myocardium].

A study was made of the effect of ethacizine, a new antiarrhythmic phenothiazint derivative, on the size of experimental myocardial infarction in rabbits 7 days after ligation of the coronary artery. Ethmozine was used as reference. Ethacizine diminished the extent of necrosis by 22.

[Effect of nonachlazine on the size of an experimental myocardial infarct].

The effect of intravenous injection of nonachlazine on the infarction size in rabbits was studied planimetrically 7 days after coronary artery occlusion. The first group rabbits received the drug 5 times every 30 minutes, beginning from the 30th minute after occlusion (the total dose 15 mg/kg). The second group rabbits were given nonachlazine 3 times a day (the total dose 12 mg/kg) during 6 days, beginning from the 2nd day after coronary artery occlusion.

On the mechanism of action of the antianginal drug nonachlazine on ischemic myocardium.

The activity of a new antianginal drug, nonachlazine, synthetized in the Institute of Pharmacology, Academy of Medical Sciences of the USSR, has been demonstrated using model myocardial ischemias on anesthetized dogs and conscious cats. Antianginal activity was evaluated by ECG, epicardial electrogram, lactate level, and lactate/pyruvate ratio in the venous blood flowing from the ischemic myocardial area. The study of the cardiotropic effect of nonachlazine provided the following findings: (1) nonachlazine enhances ino- and chronotropic functions of the heart via stimulation of its beta-adrenergic receptors; (2) nonachlazine's positive chronotropic effect is substantially less marked than the inotropic one; (3) nonachlazine decreases the intensity of chronotropic reactions of the heart induced by isopreterenol.

[Effect of etmozin on thrombocyte aggregation capacity].

It was shown in in vitro experiments that etmozin at a concentration of 100 micrograms/ml significantly suppressed (by 21%) platelet aggregation induced by ADP, but it had no effect on platelet aggregation induced by arachidonic acid. In in vivo experiments etmozin was found to cause a marked suppression of tendon collagen-induced platelet aggregation in the doses 2-5 mg/kg having antiarrhythmic activity. Under suppressed platelet aggregation induced by indomethacin, the prostaglandin biosynthesis blocker etmozin displayed no antiaggregation effect.

[Effect of nonachlazine on brain and myocardial noradrenaline content in normal rats and rats subjected to stress].

Nonachlazin causes a rapid and significant increase in the noradrenaline content of the rat myocardium and brain stem. The noradrenaline level falls in these tissues under stress reaction induced by immobilization and electric pain stimulation. Nonachlazin pretreatment before stress reaction prevents the decrease of the myocardial noradrenaline level and the development of cardiac ischemic disturbances and arrhythmias (according to the ECG data).