An assessment of the influence of 2-ethyl-6-methyl-3-hydroxypyridine succinate (Mexidol) on the physical performance of small laboratory animals and recovery after exercise was made. As a result, it was found that a single application of Mexidol increases the endurance of animals, estimated as maximum swimming time, 1.57 times. With the course of the drug, there was a tendency to improve performance with access to the plateau after the 3rd week, similar to the comparative drug - bis {2 - [(2E) -4-hydroxy-4-oxobut-2-enyloxy] -N, N-diethylethanaminium} butanedioate.

A new compound ALM-803 (trihydrochloride N¹-(3,4,5-trimethoxybenzyl)-N²-{2-[(3,4,5-trimethoxybenzyl)amino]ethyl}-1,2-ethanediamine) was synthesized as analog of ALM 802, differing from it by the position of the methoxy groups in the phenyl rings. It is established that this structural change leads to the disappearance of anti-ischemic activity and antiarrhythmic activity on the model of aconitine arrhythmia in rats, but the antiarrhythmic activity on models of chloride-calcium arrhythmia and electrical fibrillation of the heart of rats remained (1 mg/kg, intravenously).

The effect of Mexidol on physical performance of mice under the extreme conditions of the weight-loaded forced swim test and on the mental performance of rats under the conditions of a neurosis-like state caused by a functional disturbance of a defensive instrumental conditioned active avoidance reflex was studied. A single dose (50 and 100 mg/kg) or a subchronic regimen (100 mg/kg) of Mexidol administered intrapertoneally enhances the physical performance of mice similarly to mildronate (100 mg/kg). Mexidol improves the rate of operant conditioning, the preservation of the memory trace and its restoration after single or multiple instances of disruption of the conditioned active avoidance reflex, and its effect does not differ from the effect of the comparison drug piracetam (300 mg/kg).

Oxidative stress resulted to decrease in cells viability compared to the control (78 ± 5 % and 100 ± 6 %, respectively, р < 0,05). GK-2 and NGF prevented H₂O₂-induced HUVEC cells damages (95 ± 3 % for HA-2 and 97 ± 4 % for NGF vs. 78 ± 5 % for H₂O2, p < 0.05). In control the number of cells with condensed chromatin was 9 ± 2, after the addition of H₂O₂ 78 ± 9 (p < 0.05 compared with the control). The addition of NGF or GK-2 after H₂O₂ significantly reduced the number of such cells (44 ± 9 and 41 ± 8, respectively) (p < 0.05 compared to hydrogen peroxide) and prevented the development of morphological changes in nuclear chromatin. Thus GK-2, like NGF, in human endothelial cell culture HUVEC prevented the apoptosis development caused by hydrogen peroxide.

Predict of anxiolytic activity and affinity for the translocator protein (TSPO), compounds in the 1-arylpyrrolo[1,2-a]pyrazine-3-carboxamide series by QSAR (Quantitative structure-activity relationship) and molecular docking was carried out. 9 Models were created from a combination of three methods of machine learning (ASNN, FSMLR, PLS) with a different set of 2D fragmented descriptors (OEState, ISIDA, GSFrag). For the validation of the model, 5-fold cross-checking was used. For molecular docking, the following programs were used: for building 3D ligand models, Marvin software package from ChemAxon, preparation of protein 2MGY (Protein Data Bank) was performed in AutodockTools, and to establish the affinity of Autodock 4.2. In addition, a study was made of the hydrophobic correspondence in the PLATINUM web service. As a result of these studies, the most promising TSPO ligands were identified. Also, the structure-property relationship was evaluated.

The paper presents the results of studies of penetration through the hemato-encephalic barrier (BBB) of rats of three new peptide drugs -modified analogues of endogenous neuropeptides and their active metabolites created in the research Zakusov institute of Pharmacology. Discussed the main physical-chemical characteristics of study dipeptides which allow predicting the penetration of peptide compounds through the BBB. All three of the studied compounds: noopept is a peptide analog of piracetam (ethyl ether N-phenylacetyl-L-prolyl-L-glycine) with nootropic and neuroprotective activity, dilept - analoge of neurotensin (methyl ether of N-caproyl-L-prolyl-L-tyrosine) - antipsychotic wich positive mnemotropic effect and the compound GB-115 (amide N-hexanoyl-L-glycyl-L-tryptophan) - retroanaloge of cholecystokinin-4 is a selective anxiolytic with anti-alcohol effect. In experiments on rats using the method of HPLC-MS/MS was shown that noopept and its metabolite cyclo-prolyl-L-glycine (CPG) are found in brain of rats after oral administration of the substance drugs, which indicates their penetration through the BBB with coefficients K_brain/plasma 1.61 and 1.38, respectively; Dilept and its active metabolite M1, are detected in the brain of rats, which indicates the penetration of both compounds through the BBB with the coefficients the brain/plasma for dilept 2.0 and metabolite-0.5, that indicated on different mechanism of transport these compounds trough the BBB. It is shown that the anxiolytic GB-115 also penetrates through the BBB with a high coefficient K_brain/plasma - 1.41. Thus, all three dipeptide analogues of natural neuropeptides penetrate the BBB, have a high tropicity to the brain tissue of rats, which may indicate their direct influence on the brain structures involved in the realization of pharmacological effects of these drugs.

Pharmacokinetics of the GSB-106 in variety of administration ways in rats was studied. After single oral administration the test substance was determined for 4 h in the blood plasma. Half-life was 0.65 h. The GSB-106 tissue availability in high-vascularized organs (liver, kidney, spleen) was over then skeletal muscle. In brain (target-organ) that parameter was 0.05. In the 24-hour urine the parent compound was not detected and in the feces were determined of 0.0001 % GSB-106 after oral administration in dose 150 mg/kg. The absolute bioavailability of GSB-106 was 5.6 %.

Relevance. Assessment of chronic toxicity is a necessary stage of preclinical research of a newly synthesized pharmacological substance GML-1 having anxiolytic activity. The aim of present research is study of chronic toxicity of tablet form GML-1. Methods. Tablet mass of GML-1 was administered orally to males and females of rats and rabbits in doses of 1 and 10 mg / kg for one month. The appearance and the general state of animals were observed, the dynamics of body weight, feed and water consumption, behavioral reactions, rectal temperature, state of the cardiovascular system (electrocardiography, blood pressure measurement) were evaluated, hematological, biochemical and pathomorphological examinations were conducted to determine possible toxic effects and their reversibility, possible target organs and local irritant effect. Results. Parameters registered in the conducted studies did not get out the limits of the reference values for these species of animals. GML-1 did not cause any regular changes in the structure of the internal organs of rats and rabbits. Conclusion. GML-1, administered to rats and rabbits for one month orally daily in doses of 1 and 10 mg / kg, did not demonstrate toxic effects and local irritant effect.