[Comparative study of the toxicity and antiarrhythmic activity of some organic derivatives of dimethylacetamide].

A comparative study of the acute toxicity and antiarrhythmic activity of new domestic derivatives of dimethylacetamide showed that the introduction of amino and carboxylic acid residues into the structure of compounds is accompanied by reduction of the toxic properties of new substances on the average 2.73 times (p = 0.002) upon intraperitoneal introduction to animals. It has been established that the derivatives are able to prevent the formation of aconitine induced arrhythmias and eliminate the arrhythmia that occurs on the second day of myocardial infarction in dogs. Original derivatives of dimethylacetamide exhibit antiarrhythmic properties and their activity increases in proportion to the acute toxicity (r = 0.83, p = 0.0043).

[Effect of a new derivative of glutamic and apovincaminic acids on brain metabolism in post-ischemic period].

Neuroprotective properties of the new derivative of glutamic and apovincaminic acids, ethyl -(3-alpha,16-alpha)-eburnamenin-14-carbopxylate of 2-aminopentadionic acid (LHT 1-02) were studied on a model of acute brain ischemia in cats. LHT 1-02 has proved to be more effective than the reference drugs vinpocetin and glycine in preventing the reperfusive damage, which was manifested by decreased postischemic hyperglycemia, activated utilization of oxygen in the brain, and suppressed postischemic metabolic lactate acidosis. Thus, the results of this comparative study show expediency of further investigations of LHT 1 - 02 as a potential neuroprotective drug.

[Efficiency of etoxidol in treating cardiovascular disorders caused by experimental cerebral ischemia].

A complex pharmacological study of the new cytoprotector drug etoksidol in animals with the disturbances of cerebral blood circulation showed that the intravenous introduction of the drug restores autonomous nomotopic driver of rhythm, conductivity in the atria and atrioventricular connection, and refractoriness of the atrioventricular connection, which were violated a result of sharp cerebral ischemia. The new drug does not suppress the inotropic function of the heart in cats and limits the dimensions of the zone of necrosis in rats with the myocardial infarction on the background of deficiency of the cerebral blood flow.

[Actiprotective and antihypoxic action of new heteroaromatic antioxidants].

Expernents with mice showed that most of 15 new heteroaromatic antioxidant compounds possess aciprotective and antixopixic properties. Based on results of treadmill and swimming tests, actiprotective action of IBKhF-1, 11 and 14 surpassed greatly bemythil and bromanthane in ordinary conditions. Inhibitor of gluconeogenase tryptophan cancelled largely the stimulatting action of highly effective and active IBKhF-1, 2 and 11 on physical performance during treadmill exercise. Consequently, gluconeogenesis activation is one of the major components of the actiprotective action of these antioxidants. In addition, IBKhF-1, 11 and 14 excelled bemythil and bromanthane in the extreme conditions of running in hyperthermia and swimming in acute hypoxia combined with hypercapnia. IBKhF-2 and 14 were better than amtisol (standard antihypoxic agent) and bemythil against acute hypoxia in pressure chamber, whereas IBKhF-4 and 14 excelled these agents in thermal chamber.

[Investigation of anti-hypoxic action of 3-hydroxypyridine derivatives in animals with some types of experimental pathology].

Experiments with occlusion of the common carotid artery in mice demonstrated that, unlike mexidol and SK-170, single injection of new derivatives of 3-hydroxypyridine (3-HP) SK-100 and IBKhF-2, and semax have an anti-hypoxic action on the model of acute normobaric hypoxia with hypercapnia. In analogous experiments with rats the distinct anti-hypoxic action was produced by 4 new 3-HP derivatives (SK-100, SK-170, IBKhF-22 at the dose of 100 mg/kg and IBKhF-2 at the doses of 10 and 30 mg/kg--extension of life span by 25-39%), mexidol (100 mg/kg) and reference-class antihypoxant amtisol (30 mg/kg, life span expansion by 19 and 27%, respectively). A series of experiments with rats with acute pancreatitis, a distinct anti-hypoxic action was shown by SK-100, SK-170 at 100 mg/kg and IBKhF at 10 and 30 mg/kg (life span extension by 26-40%), mexidol (100 mg/kg) and amtisol (30 mg/kg) which extended life span by 17 and 22%, respectively. Therefore, SK-100 and IBKhF-2 are potent to prolong life span of equally mice and rats; SK-170 and mexidol were effective only in experiments with rats.

[Experimental study of the efficacy of apovincaminic acid derivative on the model of reperfusive cerebral damage].

Neuroprotector properties of a new apovincaminic acid derivative (LHT 2 - 02) were studied on a model of acute brain ischemia in cats. LHT 2 - 02 has proved to be more effective than the reference drugs vinpocetin and glycine in preventing the reperfusive damage, which was manifested by decreased postishemic hyperglycemia and suppressed postishemic metabolic lactate acidosis.

[Studying the mechanism of antiarrhythmic action of a tertiary derivative of lidocaine]. / Issledovanie nekotorykh aspektov mekhanizma protivoaritmicheskogo deistviia tretichnogo proizvodnogo lidokaina.

The investigation of electrophysiological parameters of the cardiac activity in cats showed that, a derivative of lidocaine with glutamic acid (anion), does not influence the cardiac pacemaker and the myocardial excitability of atrium and ventricles, but decreases the atrioventricular conduction and increases the refractory period of myocardium in the left ventricle of intact heart. Under the conditions of myocardial ischemia, LKhT-3-00 exhibits a negative chronotropic effect. Lidocaine glutamate increases the refractory period of atrium and decreases the excitability and refractory period of ventricles.

[Effect of a nibentan derivative LKhT53-91 on the heart electrophysiological parameters]. / Vliianie proizvodnogo nibentana LKhT53-91 na élektrofiziologicheskie parametry serdtsa.

The compound LKhT5391 (a derivative of nibentan) affects the electrophysiological cardiac parameters to a lower extent than does nibentan. Administered in an effective antiarrhythmogenic dose (comparable with the effective dose of nibentan), LKhT5391 produces a less pronounced and shorter negative chronotropic action than does nibentan. The negative dromotropic effect of the compound studied is manifested only in the atrioventricular node, while not influencing conductivity through the atria and ventricles.

[The anti-arrhythmia activity of amino acid-containing trimecaine derivatives on models of early occlusive and reperfusion arrhythmias in cats]. / Protivoaritmicheskaia aktivnost' aminokislotsoderzhashchikh proizvodnykh trimekaina na modeliakh rannikh okkliuzionnykh i reperfuzionnykh aritmii u koshek.

Experiments were conducted on models of early occlusion and reperfusion arrhythmias in cats to study the antiarrhythmic activity of trimecain, its morpholine analogue (MPT), and MPT derivatives containing glycine, magnesium salt of aspartic acid, and N-acetylglutaminic acid. All the compounds were injected in doses of 5% of LD50. A 22.5 mg/kg dose of trimecain prevented cardiac rhythm disorders after occlusion of the coronary arteries as well as after restoration of the coronary blood flow. Replacement of the diethyl group in the structure of trimecain by the morpholine ring led to diminution of antiarrhythmic activity, and MPT in a dose of 28.0 mg/kg, in distinction from the former, had no effect on the frequency of the occurrence of early occlusion arrhythmias and the duration of reperfusion arrhythmias. Introduction of amino acids as an anion into the MPT structure raised the antiarrhythmic activity of the last named.

[The first original Russian class-III antiarrhythmic nibentan]. / Pervyi original'nyi otechestvennyi antiaritmik III klassa nibentan.

The paper presents experimental and clinical findings of the new antiarrhythmic drug nibentan. The agent was found to be a class-III antiarrhythmic agent in terms of its electrophysiological effects and an inhibitor of the delayed rectifier potassium current in terms of its effects on the ionic channels of cardiomyocytes. The clinical trial of nibentan shows that the drug is highly effective (in 70-100% of cases) in patients with atrial flutter and fibrillation and in those with supraventricular tachycardia and it is less effective in suppressing ventricular premature contractions and tachycardia. The rate of arrhythmogenic effects produced by the drug was inversely related to its antiarrhythmic action. Nibentan has been approved for clinical use.