NGF at a concentration of 100 ng / ml when added 24 hours before 6-OHDA and after damage completely prevented the development of the damaging effect of neurotoxin. Dipeptide GK-2 at a concentration of 10−5 M, similar to NGF, showed a protective effect on the cellular model of Parkinson's disease. According to the Western blot analysis NGF increased the level of BDNF in the HT-22 cells 1.6 times compared to the control, and dipeptide GK-2 at a concentration of 10−8 M — 1.4 times compared to the control.

The purpose of this work was to study the effect of dimeric dipeptide mimetics of the 1st, 2nd and 4th loops of BDNF – GSB-214 (heptamethylenediamide bis-monosuccinyl-methionyl-serine), GTS-201 (hexamethylenediamide bis-hexanoyl-seryl-lysine) and GSB-106 (hexamethylenediamide bis-monosuccinylseryl-lysine) on the proliferation of the HT-22 hippocampal cells using MTT-assay. It has been established that the mimetics of the 1st, 2nd and 4th loops of BDNF after incubation with HT-22 cells for 48 and 72 hours did not affect their proliferative activity.

The antibacterial properties of zinc citrate are important for the treatment and prevention of pathologies caused by bacterial and viral pathogens. The trace element zinc exerts a suppressive effect on pathogenic microbiota and supports various aspects of beneficial microflora. However, the mechanisms of this "dual" action of zinc on microbiota are poorly understood. An analysis of 5,103 publications on the antibacterial effects of zinc salts provided a logical justification for zinc's selective bacteriostatic and bactericidal action against pathogenic flora: (1) zinc salts (e.g., zinc citrate), included in probiotics (e.g., Acipol Forte), support beneficial microbiota (lactoand bifidobacteria), which, in turn, displace pathogenic microbiota; (2) zinc supports humoral and cellular immunity in the host; (3) differentiated, genetically determined effects of zinc compounds on specific strains of bacterial pathogens and beneficial microbiota.

Relevance. Medicines can cause the body to lose magnesium and pyridoxine (vitamin B₆), which leads to the formation of side effects and worsens the course of the underlying disease.

Objective. Evaluation of the antimicronutrient effect of all drugs registered in the ATX rubricator using chemoreactome screening.

Materials and methods. Using methods of topological data analysis and labeled graph analysis, a systematic computer analysis of databases (SIDER, FAERS, PubChem, HMDB) was performed, algorithms for predicting magnesium-excreting and pyridoxine-excreting properties of drugs were developed, followed by screening of 2527 ATC drugs.

Results. The accuracy of the algorithms in cross-validation was 94–98 % for magnesium deficiency and 88 % for vitamin B₆ deficiency. On average, each drug accounts for 8.5±6.5 antimicronutrient effects. Only 4 % of drugs did not show a negative effect on micronutrient metabolism. Pyridoxine deficiency is caused by 1701 drugs (68 % of ATC), magnesium deficiency — by 1064 drugs (42 %). The most negative impact on the homeostasis of both micronutrients is exerted by antibiotics (J01), psychotropic drugs (N05, N06), antineoplastic agents (L01), hormones (G03), diuretics (C03), analgesics (N02) and antiinflammatory drugs (M01).

Conclusion. The results of chemoreactome screening will allow us to reasonably recommend accompanying various pharmacotherapy with drugs based on pyridoxine and organic magnesium salts.

Background. Cognitive impairment and anxiety are common side effects of anticancer chemotherapy, particularly with doxorubicin (DOX). Therefore, there is a need to develop experimental models to assess DOX-induced dose-dependent impairments in cognitive function and emotional behavior.

The aim — study of the dose-dependent effect of the anthracycline antitumor drug doxorubicin (DOX) on the formation and reproduction of a memory trace, anxiety, and motor responses in experiments on healthy sexually mature rats.

Materials and methods. The experiments were performed on outbred male rats that were administered DOX (2.0 and 3.0 mg/kg, intraperitoneally) once a week for 4 weeks. To record exploratory behavior, assess motor reactions and anxiety behavior, the following tests were used: “open field”, “rotary rod”, “horizontal bar” and “elevated plus maze” (EPM). The influence of DOX on the processes of learning and reproduction of a memory trace was studied in the test of the conditioned reflex of passive avoidance (CPAR).

Results. DOX at doses of 2 and 3 mg/kg did not affect rat behavior in the open field test and did not impair motor coordination in the rotarod and horizontal crossbar tests. In the EPM test, DOX (3 mg/kg) increased anxiety response. DOX at a dose of 2 mg/kg, which does not induce anxiety, did not affect rat learning in the CPAR test. However, after 24 hours and 7 days, DOX (2 mg/kg) reduced the latency time of entry into the dark compartment of the setup compared to the control, which indicates a disruption in the reproduction of the CPAR.

Conclusion. The obtained data confirm the validity of using DOX (2 mg/kg) for modeling cognitive impairment and anxiety at the stage of preclinical study of biologically active substances.

Introduction. The compound ALM-802S, which has a pronounced cardiotropic effect, has been identified among the alkoxyphenyltriazoalkanes. The structure of this substance includes 2 pharmacophore components of the cardioprotective agent trimetazidine, which can potentially cause extrapyramidal disorders. The ALM-802S compound, in addition to its cardiotropic activity, has anxiolytic and analgesic effects. It is possible that the ALM-802S compound, acting on the central and peripheral serotonergic and dopaminergic mediator systems, may, like trimetazidine, cause central side effects.

The study aim. It was to evaluate the effect of the ALM-802S compound on the content of biogenic catecholamines, indolamines and their metabolites in blood plasma and separate brain structures in rats.

Materials and methods. The experiments were carried out on white male rats weighing 180–200 g. The test substance was administered at a dose of 5 mg/ kg i./p. 60 minutes before decapitation. The content of indolamines and catecholamines in blood plasma and brain structures was determined using HPLC/ED.

Results. Analysis of the obtained data showed that the compound ALM-802S with a single systemic administration does not affect the content of indolamines in blood plasma and brain structures of rats. Measurements of the catecholamine content showed that the ALM-802S compound significantly reduced the concentration of DOPA and HCV in blood plasma, the content of A, HA, DA, DOPA and the ratio of metabolites remained virtually unchanged. Of all the studied brain structures, only in the hypocampus there was a decrease in the GVK/DA ratio, which characterizes the DA decay rate. No changes were found in the rest of the brain structure.

Conclusion. Using neurochemical analysis, information was obtained on the absence of a pronounced effect of ALM-802S on the functional activity of the central dopaminergic and serotonergic systems, which minimizes the possibility of extrapyramidal disorders and the development of drug dependence when using ALM-802S in therapeutic doses.

A new dimeric dipeptide mimetic with antidepressant-like activity has been developed at the FSBSI "FRC of Original and Promising Biomedical and Pharmaceutical Technologies". A specific, sensitive, fast and reproducible method for the determination of bis-(N-monosuccinyl-L-asparaginyl-L-asparagine hexamethylenediamide (GTS-301) in rat blood plasma using high-performance liquid chromatography tandem mass spectrometric detector has been developed and validated. The lower limit of quantification in blood plasma was 50 ng/ml. All calibration curves were described by a quadratic equation (correlation coefficient averaged 0.996, n = 3) in the concentration range of 50÷10000 ng/ml. The accuracy values for the quality control samples varied throughout the day from an average of 93.2 to 113.3 %. The precision ranged from 1.1 to 11.4 %. During the validation period, the accuracy values averaged 101.1–108.8 % and accuracy — 5.4–7.3 %. For the calibration standards, the values of the validation parameters were also within acceptable values (accuracy — 92.2–106.8 %, accuracy — 0.1–11.5 %). The results of the dilution study of experimental blood plasma samples with intact biomaterial in 10and 100-fold lie within the acceptable values of 85–115 %. It has been established that GTS-301 is stable in the biological material at ambient temperature for short-term storage (3 hours), exposure to a thermostatically controlled autosampler (5 °C) during an analytical experiment (up to 20 hours), and prolonged storage at -50 °C (for 4 weeks), and also if subjected to several freezing/defrosting cycles (3 cycles). Thus, the above-mentioned characteristics of the developed technique make it suitable for use in preclinical pharmacokinetic studies. The pharmacokinetics of GTS-301 in rat blood plasma after a single intraperitoneal injection at a dose of 150 mg/kg was described.

Relevance. Breast cancer resistance protein (BCRP) is one of the main clinically significant transporter proteins that play an important role in the pharmacokinetics of drugs. To predict the development of drug interactions at the level of this transporter, it is recommended to test drugs for belonging to substrates and BCRP inhibitors.

Objective. Comparative assessment of the effect of ethylmethylhydroxypyridine succinate (EMHPS) on the activity of the BCRP transporter protein under in vitro conditions using sulfasalazine as a substrate.

Materials and methods. The study was performed in vitro on Caco-2 cells that were cultured in a transwell-system. Sulfasalazine was used as a BCRP substrate. EMHPS was used in the concentration range of 0.1 — 500 µM. A classic BCRP inhibitor, quercetin, was used as a comparison drug. The concentration of sulfasalazine in the transport medium was determined by HPLC-MS/MS.

Results. During the study, it was shown that EMHPS inhibited BCRP activity in the concentration range of 50–500 µM. In terms of inhibitory activity, the tested drug was inferior to the comparison drug quercetin — the IC₅₀ of quercetin was 0.2 µM, the IC₅₀ of EMHPS was 37.5 µM. To study the clinical significance of the inhibitory ability of EMHPS, the ratio C_max of EMHPS/IC₅₀ (predicts systemic inhibition of BCRP in the liver, kidneys, and histohematic barriers) and the ratio dose of EMHPS/ 250 ml / IC₅₀ (predicts inhibition of BCRP in the intestine) were calculated. It has been shown that EMHPS can clinically significantly inhibit BCRP in the intestine.

Conclusion. Thus, EMHPS is an inhibitor of BCRP in vitro. To confirm the significance of the obtained results for the development of drug-drug interactions, it is necessary to conduct clinical studies.

The introduction of bioethical principles into scientific biomedical research necessitates the search for and development of new alternative models, including those for screening potential pharmacological compounds. The main difficulty in developing alternative biomodels is the creation of a condition or pathology as close as possible to human ones both in terms of the mechanism of development of such a process and in terms of the response to pharmacological correction. Hydrobionts, possessing physiological reactions comparable to higher animals, have, among other things, organs and tissues similar in structure and functionality and have very great potential for screening studies and experimental pharmacology. They satisfy modern ethical concepts and norms limiting the scope of use of higher animals in experimental research. The article presents the results of work on the creation of an alternative model of Danio rerio for assessing the thermoand frigoprotective properties of pharmacological compounds. The possibility of modeling hypoand hyperthermia states in fish under laboratory conditions is demonstrated. A scoring system for assessing the condition of fish has been developed. Criteria for assessing hypoand hyperthermia are defined. Pharmacological validation of the developed model was conducted using reference drugs. The model's potential for screening the thermoand frigoprotective activity of pharmacological compounds was demonstrated.