No 2 (2017)
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STUDIES OF THE MECHANISM OF ACTION OF DRUGS
I. B. Tsorin,
V. P. Zinchenko,
I. Yu. Teplov,
A. M. Kosenkov,
Yu. I. Murinov,
M. S. Yunusov,
S. A. Kryzhanovskii
4-11 592
Abstract
In vitro experiments performed on the isolated rats hippocampal neurons, the antiarrhythmic activity electrophysiological mechanisms of the complex compound LMG-124 containing an antiarrhythmic agent of the class I by Vaughan Williams, Lappaconitine hydrobromide, were studied. As the reference preparation, a prototype, Lappaconitine hydrobromide, was used. The electrical activity of the neurons was recorded by the patch-clamp method in the whole cell configuration. It is shown that the compound LMG-124 effectively inhibits the fast incoming Na+ current flowing through transmembrane potential-dependent fast Na+ channels. This effect of the LMG-124 connection is realized at the level of the open Na+ channel. As follows from the data obtained, the LMG-124 compound, in contrast to Lappaconitine hydrobromide, blocks not only Na+ channels, but also partially and K+ channels, so that it can be attributed to antiarrhythmic drugs potentially possessing anti-arrhythmic properties of the Ia class by Vaughan classification Williams.
PHARMACODYNAMICS STUDIES
V. N. Stolyaruk,
I. B. Tsorin,
M. B. Vititnova,
T. D. Nikiforova,
Yu. I. Murinov,
M. S. Yunusov,
S. A. Kryzhanovskii
12-15 675
Abstract
Two models of the aconitin-induced cardiac arrhythmias were used to compare the antiarrhythmic and antifibrillatory activity of the reference drug Lappaconitine hydrobromide and the LMG-124 compound. It is shown that both compounds have antiarrhythmic action. At the same time, the compound LMG-124 realizes its antiarrhythmic effect in a significantly lower dose. In this case, the compound LMG-124 shows a pronounced antifibrillatory activity, in contrast to the reference drug Lappaconitine hydrobromide, which in the studied dose does not exhibit similar activity.
V. N. Stolyaruk,
I. B. Tsorin,
M. B. Vititnova,
V. P. Gusev,
Yu. I. Murinov,
M. S. Yunusov,
S. A. Kryzhanovskii
16-18 523
Abstract
The antifibrillatory activity comparative study of the compound LMG-124 and the reference drug Lappaconitine hydrobromide was performed on the model of reperfusion arrhythmias. Both drugs are shown to exhibit antiarrhythmic and antifibrillatory activity, but the compound LMG-124 realizes its effect in a significantly lower dose.
19-24 997
Abstract
Anxiolytic effects of dipeptide endogenous cholecystokinin tetrapeptide analogue GB-115 at the dose range 0,25-2,0 mg/ kg after oral administration were studied in rodents with high emotionality. In “elevated plus-maze” test GB-115 anxiolytic activity comparable with phenazepam was shown in inbred “anxious” BALB/c mice and “aged” rats with long-term 10% ethanol experience during ethanol withdrawal. GB-115 at the doses 0,5-2,0 mg/kg didn’t induce sedation, in contrast phenazepam significantly suppressed spontaneous locomotor activity in BALB/c mice in Optovarimex. The data obtained show potent anxiolytic properties GB-115 (tablet 0,001) lacking benzodiazepine’s side-effects in animal models with high emotionality.
25-29 659
Abstract
The study was aimed to compare the psychopharmacological effects of 2 anticonvulsant drugs levetiracetam ((S)-2-(2-oxopyrrolidin-1-yl) butanamide) and the new compound, GIZh-290 (2-oxo-4-phenylpyrrolidine-1-yl) acetic acid) on behavioral spectra of inbred mice BALB/c and C57BL/6 under conditions of "closed cross-maze" test. It was found that after 5-fold i.p. injections levetiracetam (600 mg/kg/day) reduced the cognitive and motor ability of C57BL/6 mice, while in BALB/c mice the drug increased anxiety and diminished motor activity. In contrast, the substance GIZh-290 (5 mg/kg/day, i.p.) had no effect in C57BL/6. Compound GIZh-290 (5 mg/kg/day, 5 days, ip) does not affect the behavior of C57BL/6 mice, but depressed the motor activity in BALB/c mice.
PHARMACOKINETICS STUDIES
Pharmacokinetic comparative study of tropoxine metabolite in miscellaneous animal species and humans
V. P. Zherdev,
G. B. Kolyvanov,
A. A. Litvin,
P. O. Bochkov,
R. V. Shevchenko,
O. G. Grybakina,
T. S. Ganshina
30-34 552
Abstract
Results of pharmacokinetic study of tropoxine metabolite (tropinone oxime; M-1) in experimental animals (rats, rabbits) and humans after administration several doses of tropoxine. Comparative analysis of the pharmacokinetic parameters characterizing of the metabolite formation intensity, i.e. Cmax of metabolite M-1 in the blood plasma increased in series: rats>humans> rabbits. Elimination rate of M-1 was decreased in series: rats>rabbits>humans
METHODS FOR DETERMINATION OF DRUGS IN BIOLOGICAL MATERIAL
35-38 639
Abstract
The article describes a method of quantitative analysis of III generation gistamine antagonist - fexofenadine in human bLood plasma by HPLC with UV detection at 220 nm. The analysis was performed in isocratic mode using Stayer chromatography system and a reversed-phase column Phenomenex Synergi 4u PoLar-RP 80A (250 х 4,6, 4 |±m) and a mobile phase (acetonitriLe-water-gLaciaL acetic acid-triethyLamine in the ratio 267-128-4,7-7) at pH 6,1. The retention time of fexofenadine was 14,70±0,04 min. Fexofenadine extraction from pLasma carried using acetonitriLe (2 mL pLasma and 4 mL acetonitriLe) by shaking on Shaker apparatus at 400 voL/min for 15 minutes, centrifuging at 3 500 rpm. for 15 minutes and evaporation of the supernatant on a vacuum rotary evaporator at 50 °C. The recovery was 84,14%. The deveLoped method is characterized by sensitivity, specificity, ease of impLementation, reproducibiLity and Linearity in the range of pLasma concentrations during oraL administration of 180 mg of fexofenadine (ALLegra coated tabLets, 180 mg, Sanofi-Aventis, USA) heaLthy voLunteers.
ORIGINAL EXPERIMENTAL RESEARCH
O. A. Nazarenko,
O. A. Gromova,
T. R. Grishina,
I. Yu. Torshin,
V. I. Demidov,
I. K. Tomilova,
E. L. Aleksakhina,
I. V. Gogoleva
39-44 488
Abstract
The results of experimental investigations of the effects of Laennec on chronic iron overload. Long-term (2 weeks) application of iron sulfate or iron polymaltose complex composition caused chronic iron overload (hemosiderosis). The liver and kidneys is more pronounced when using iron sulfate and a few less - when using polymaltose complex. Laennec decreased the damage of hepatocytes (decreased ALT levels). According to histological analysis application Laennec reduced iron deposition in the liver and kidneys and completely prevented the formation of iron deposits in the brain.
LITERATURE REVIEW
45-55 1165
Abstract
The state of chronic stress caused by various exogenous factors, is always accompanied by a state of excitation in the Central nervous system, neurodegenerative disorder of body functions, impairment of metabolic and physiological processes, immune abnormalities. To increase stress tolerance it is necessary to maintain the body's balance functions of the nervous, immune, endocrine and antioxidant systems of the monooxygenase. The analysis of Literature data and results of own researches of the authors give grounds to conclude that higher stress can be achieved by reducing the Level of free radical oxidation, optimization of Lipid-choLesteroL and hormonal status when using anti-stress drugs of new generation, which incLude organic Lithium saLts. UnLike many synthetic tranquiLizers and sedatives, acting on the neuroreceptors, organic Lithium saLts affect mentaL activity, without affecting neuroreceptors unit of the brain, and are invoLved in the reguLation of neurosynaptic activity through inhibition of enzymes responsibLe for the main metaboLic degradation pathway of gamma-aminobutyric acid - inhibition of GABA-decarboxyLase and GABA-aminotransferase. There is reason to beLieve this method of increasing stress resistance are not onLy more effective but aLso more physioLogicaL Compound organic Lithium saL with ascorbic acid, combined effect on neurohumoraL status and normaLize it, with the effect of their use is the resuLt of decrease LeveL of free radicaL oxidation, incLuding Lipid peroxidation. Lithium ions, contribute to the maintenance of normaL excitabiLity of CentraL nervous system and bLood vesseL tone by reducing the excessive concentration of norepinephrine in the CentraL nervous system and normaLization of the LeveL of sodium ions in nerve and muscLe ceLLs. The compLex nature of neyroLepticheskih of action of Lithium is due to the existence of muLtipLe pathways of exposure to Lithium ions on physioLogicaL processes. With sufficient suppLy of Lithium sensitivity of the brain to dopamine increases. Lithium ions have an effect on the homeostasis of neurotransmitters, and increase the synthesis of neurotrophic factors and the sensitivity of ceLLs of the nervous system to their effects. Further study of the physioLogicaL action of organic saLts of Lithium wiLL aLLow to expand representations about the mechanism of antistress action of drugs of this type and to outLine ways of enhancing the stress resistance of humans and animaLs in the treatment and prevention of depressive and subdepressive States.
ISSN 2587-7836 (Print)
ISSN 2686-8830 (Online)
ISSN 2686-8830 (Online)