The article presents an analysis of publications on myoinositol in order to clarify the possibilities of prescribing drugs based on it. Myoinositol is one of the endogenous human metabolites that has a significant effect on the functioning of cells and tissues of the whole body. The main function of myoinositol and its derivatives is to participate in intracellular signal transmission and ensure the functioning of such important receptors as insulin receptors, catecholamines, metabotropic receptors of various neurotransmitters, growth factors, etc. (Myoinositol is the basis for the synthesis of an important group of signaling molecules, inositol phosphates, which mediate signal transmission from growth factor receptors and neurotransmitters). Most inositol-dependent proteins with known functions are necessary for the vital functions of the cardiovascular, immune system, and connective tissue structure. Equally important is the role of myoinositol in maintaining the functioning of the central nervous system (including neurotrophic and neuroprotective roles), sugar metabolism (primarily the signaling cascade of insulin) and the functioning of the kidneys and liver. Myoinositol subsidies contribute to the prevention of folate-resistant malformations and neuroprotection of the brain under stress.

Relevance. The nerve growth factor (NGF), possessing neuroprotective and neuroregenerative properties, holds promise for the development of medications for the treatment of post-stroke conditions. At the Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies, a dimeric dipeptide mimic of NGF with the laboratory code GK-2 was designed and synthesized. Under conditions of experimental cerebral ischemia, it significantly reduced the volume of brain infarction and stimulated neuro- and synaptogenesis.

Objective. The aim of this study was to investigate the effects of GK-2 on experimental post-stroke dementia and depression.

Methods. Ischemic stroke was induced by occlusion of the middle cerebral artery (MCAO) in Wistar rats. GK-2 was administered intraperitoneally at a dose of 0.5 mg/kg for 21 days post MCAO. Short-term and long-term memory of the animals were assessed 30–40 days post MCAO using the novel object recognition test. Depressive-like state was evaluated through the forced swimming test and sucrose preference test.

Results. In animals subjected to MCAO, both short-term and long-term memory exhibited a statistically significant decline of 80 %, along with a depressive-like state characterized by a 50 % increase in total immobility time and a 30 % reduction in sucrose preference, when compared to the sham-lesioned group. Dipeptide GK-2 completely averted the onset of these impairments.

Conclusion. The dipeptide mimic of NGF, GK-2, mitigates the development of cognitive and psychomotional impairments in the setting of experimental stroke.

The purpose of the study is a theoretical justification (working hypothesis) of a possible approach to calculating doses in a combined medicinal product containing 2 pharmaceutical substances. A mathematical model is proposed, which is a multiple regression equation from two variables, which is a square polynomial. The proposed model makes it possible to calculate the optimal doses of pharmaceutical substances in a combined drug by further differentiating the regression equation in partial derivatives. Two examples of dose calculation are presented.

The pharmacokinetics of a new antiparkinsonian drug ADK-1113 after single intravenous and intragastric administrations in mice at doses of 10 and 20 mg/kg was studied. The absolute bioavailability was 10.1–16.3 % that indicates on potential possibility of preparing a dosage form for oral administration.

Relevance. Planning the design of bioequivalence clinical studies of generic highly variable drugs requires non-standard approaches – the use of replicative (repeated) or adaptive design. However, both approaches entail an increase in organizational, time, and financial costs. Therefore, it becomes relevant to search for ways to pre-select volunteers with a lower initial level of variability in pharmacokinetic parameters to reduce the number of subjects.

Objective. The aim of this study was to determine the potential subjects in clinical trials with a low initial level of variability in pharmacokinetic parameters using methods for assessing initial gender – age and anthropometric and clinical laboratory parameters.

Material and methods. Data from clinical studies of the bioequivalence of drugs (valganciclovir, carebastine and raltegravir) with different levels of variability conducted in the period 2020–2022 in Russia were used for analysis. To achieve this goal, a model for grouping pharmacokinetic parameters (PhK) with known demographic and clinical laboratory parameters was developed using discriminant analysis. Discrimination was performed between optimal pharmacokinetics (OPhK) and variable pharmacokinetics (VPhK). Mathematical and statistical analyses of the results were performed using Microsoft Excel 2013 and Statistica 10.0.

Results. During the study, the variability of the maximum concentration of the drug in plasma (C_max), including its logarithmic values, was used as a basis. The levels of intra-individual variability (CV_intra), which is the main characteristic of drug variability, in the OPhK group were several times lower than those in the VPhK group for all studied drugs, but for the highly variable drug raltegravir, they differed by almost 10 times.

Conclusion. Therefore, the obtained results indicated that using traditional gender – age and anthropometric indicators alone is impossible to separate the OPhK and VPhK groups for the analyzed drugs with high PhK variability.

Eight important biotargets of biaromatic cardioprotective drugs were selected in this work: calcium Cav1.2-channel, sodium Nav1.5-channel, potassium hERG-channel and Kv1.5-channel, HCN-channel, β1-adrenergic receptor, ryanodine RyR2-receptor and σ1-receptor. Biaromatic ligands databases were collected for each of them, on the basis of which their pharmacophore models were calculated in the Phase Schrödinger program. Using the PhaseScore function, we analyzed the correspondence of previously synthesized and studied bis-arylazaazlkanes to calculated pharmacophore models. It was found that the vastmajority of molecules have a correspondence of more than 50 % to all models, which indicates a high probability of the involvement of these biotargets in the possible cardioprotective effects of bis-arylazaazlkanes, and also confirms the hypothesis of the multitargetability of substances with this structure.

7-hydroxymatairesinol (7(OH)MR) is the main lignan of spruce extracts, characterized by oncoprotective and anti-inflammatory properties. The results of chemoreactome modeling made it possible to formulate the molecular mechanisms of the pharmacological effects of 7(OH)MR for anti-inflammatory (inhibition of 5-lipoxygenase, matrix metalloproteinase MMP2, mitogen-activated kinase p38-alpha, leukotriene b4 receptor, prostacyclin receptor), oncoprotective (antioxidant effect due to inhibition heme oxygenase-2, inhibition of cyclin-dependent kinases 3 and 4, epidermal growth factor, mTOR protein). An assessment of the transcriptomic effects of 7(OH)MR in breast cancer cells showed significant dose-dependent effects on the transcription of 3468 of 12700 genes. The 7(OH)MR molecule, reducing the expression of proliferative genes (401 genes) and chronic inflammation (148 genes), while simultaneously increasing the transcription of oncoprotective immunity genes (100 genes), inhibits the proliferation of tumor cells. Experiments on solid Ehrlich carcinoma showed a significant oncoprotective effect of 7(OH)MR at doses of 60, 120 mg/day, even while taking estrogen (p = 0.007). A clinical study showed that 7(OH)MR (60 mg/day, 1 month) helps normalize estrogen metabolism and improve the clinical symptoms of mastopathy.