The aim of the work was to conduct an analysis of the current state and current trends in the approval of drugs, as well as some aspects of the methodology for their development based on biological molecules and registration.

Materials and methods. The material for the analysis was taken from the abstract databases of PubMed, Google Scholar and e-library.ru. The search was carried out using publications for the period from 2008 to 2023, the keywords were as follows: “biologicals”, “new drug approval”, “drug authorization”, “drug development”, “biosimilar”, taking into account various spellings.

Results. Over the past 15 years, scientists have been observing revolutionary trends and processes in the field of the drug development, especially biopharmaceuticals. Significant advances have been made in gene, immune and cell therapies, resulting in the approval of such drugs more than doubling over the past ten years. The development of biological drugs includes the identification and testing of molecular targets and requires a deep understanding of the structure and functioning of the polypeptides involved in the development of the effect. The features of these active pharmaceutical substances are a high molecular weight, a complex three-dimensional structure and a high immunogenic potential. Preclinical and clinical studies of biologics have unique challenges. Selecting appropriate animal species, understanding the immunogenicity, and assessing pharmacodynamics and toxicological properties require a multilevel, detailed approach. The article discusses the regulatory framework under which these drugs are registered, summarizing the guidelines provided by international organizations such as the International Council for Harmonization and various national agencies.

Conclusion. The analysis highlights the current advances and prospects in the development of biologics, highlighting their key role in future transformations in the treatment of rare diseases and oncology, approaching the era of personalized medicine. Monitoring the development directions and technological approaches, as well as the commitment to global methodological and regulatory aspects can become a catalyst in the development of the Russian pharmacology.

The aim of the work was to analyze the current research state of phenylpropanoids as a special specific class of biologically active compounds and the prospects for their use for the development of medicines and biologically active food additives.

Materials and methods. The scientific data for the period from 1968 to 2023 were studied in the databases of Scopus, ScienceDirect, PubMed, Google Scholar, e-library.ru, ResearchGate – a scientific information network. Herewith, the following keywords were used: “phenylpropanoids”, “antioxidants”, “hepatoprotectors”, “immunomodulators”, “organoprotectors”, “anxiolytics”, “adaptogens”, “preventive medicine”, “sanogenesis”, “medicines”, “biologically active food additives”, “sports medicine” and their English-language analogues.

Results. This scientific research examines the main stages and results of studying the class of phenylpropanoids in the following aspects: a chemical structure and classification, biosynthesis and its role in the biogenesis of other classes of phenolic compounds, their distribution, biological and pharmacological activity in the plant world, the search for plant sources and their use in medicine and pharmacy. The existing and potential applications of phenylpropanoids for preventive and therapeutic purposes are discussed.

Conclusion. The analysis of the scientific publications on the pharmacognostic and biomedical studies of the medicinal plants containing phenylpropanoids, substantiates the expediency of considering them as an autonomous specific class of biologically active compounds. The organoprotective profile of their action and a wide range of specific pharmacological activities of phenylpropanoids are connected by common links of the sanogenesis in the “prooxidant–antioxidant” system. The choosing of promising plant sources for the development of medicines and biologically active compounds with specified properties is justified from the dependence position of “chemical composition – structure of compounds – spectrum of activity”.

A chronic form of osteoporosis (OP) substantiates a long-term pharmacotherapy of patients, which increases the risk of adverse drug reactions (ADRs) during the therapy. The enhancement of requirements to the quality of safety monitoring carried out in the context of pharmacovigilance and the newly identified safety problems require an improvement of the system of quality control of medicinal products (MPs).

The aim of the work was to review the application of a new promising method for monitoring the drug safety – the system of Drug-Related Problems (DRP) in the osteoporosis pharmacotherapy.

Materials and methods. The following databases and search engines were used to retrieve scientific papers by Russian and foreign authors: PubMed, elibrary.ru, Google Scholar, CyberLeninka, Russian National Library. The information sources were searched using the following keywords and word combinations: “drug-related problems”, “drug safety”, “osteoporosis” (in Russian and English, respectively), as well as the corresponding MeSH terms.

Results. The application of DRP system in the health care of different countries was reviewed, and the risk factors of the problems associated with the use of MPs, the appropriate interventions in case of the detection of high DRP values were investigated. The study of the problems associated with the use of MPs for the treatment of OP during the complex pharmacotherapy made it possible to determine the feasibility of using this method to improve the safety and effectiveness of this kind of treatment in patients.

Conclusion. The analysis of emerging DRPs makes it possible to increase patients’ adherence to the treatment and stop the ADRs. This improves the quality of life of patients and increases the effectiveness of pharmacotherapy. The introduction of such a method of the drug safety research into the system of pharmacovigilance of the Russian Federation is an important step in the development of personalized medicine. A further study of problems associated with the use of drugs in OP patients will also help to reduce the risks arising during the combination pharmacotherapy.

Rheumatoid arthritis (RA) is a systemic inflammatory disease affecting mainly small and major joints. The development for new drugs for the treatment of RAs is constantly underway, while the purposeful synthesis of multi-targeted small molecules can be considered a promising direction for the synthesis of new anti-rheumatic drugs.

The aim. To evaluate the anti-inflammatory and antiresorptive effects of acyl substituted chromone derivatives in experimental animal model for rheumatoid arthritis.

Materials and methods. RА was modeled in rats by injection of a suspension of human type II collagen and a complete Freunds adjuvant (in a ratio of 1:1) under plantar aponeurosis of the hind limb of the animal. The analyzed substances under ciphers X3A7 and X3A9 at a dose of 20 mg/kg and the reference drug dexamethasone at a dose of 3 mg/kg were administered intraperitoneally for 28 days from the moment of RA modeling. On the 7^th, 14^th, 21^st and 28^th days of the experiment, the severity of the clinical manifestations of RA was determined. After 28 days, changes in the content of cytokines in the rats blood serum were assessed: tumor necrosis factor-α (TNF-α), interleukins (IL-1, IL-6, IL-10 and IL-12). Changes of myeloperoxidase activity and concentrations of matrix metalloproteinases (MMPs) of type 2 and 9 were determined in synovial tissues.

Results. During the study, it was shown that the use of the tested compounds X3A7 and X3A9, as well as the reference, contributed to a decrease in the severity of clinical manifestations of RA, starting from the 14^th day of the experiment. Subsequently, it was demonstrated that in animals treated with dexamethasone, the cytokine content in blood serum decreased in relation to untreated animals: TNF-α – by 57.8% (p <0.05), IL-1 – 64.1% (p <0.05), IL-6 – 59.1% (p <0.05) and IL-12 – 72.3% (p <0.05), with an increase in the level of IL-10 – by 75.4% (p <0.05). The cytokine profile of the blood serum changed similarly when the studied compounds were administered to animals. It worth be noting that against the background of the administration of dexamethasone, X3A7 and X3A9 substances, the activity of myeloperoxidase decreased by 41.7 (p <0.05), 61.7 (p <0.05) and 65.0% (p <0.05), respectively, while the concentration of MMP2 decreased by 24.0 (p <0.05), 38.5 (p <0.05) and 34.4% (p <0.05), respectively, and MMP9 – by 13.5 (p <0.05), 37.9 (p <0.05) and 35.6% (p <0.05).

Conclusion. The study showed that the administration of the analyzed chromone derivatives X3A7 and X3A9 suppresses inflammatory reactions and resorptive processes in synovial tissues, which can serve as a basis for their further study as antirheumatic agents.

The study is focused to the investigation of a new kappa-opioid agonist RU-1205, which exhibits an analgesic effect without causing dysphoric or aversive actions. It is assumed that this effects may be due to its functional selectivity, or the presence of an additional mechanism of action that involves blocking p38 mitogen-activated protein kinase (MAPK).

The aim of the study was an experimental identification of RU-1205 mechanisms of action associated with the inhibition of MAPK p38 and functional selectivity for kappa opioid receptors.

Materials and methods. The LFP activity was recorded in the male rats weighing 260–280 g (n=62) and implanted with chronic cortical and deep electrodes, after the intracerebroventricular administration of the well-studied reference substances: the selective kappa-opioid agonist U-50488 100 μg; the MAPK p38 blocker SB203580 1 μg; and the investigational compound RU-1205 at 350 μg. The weighted phase lag index (WPLI) was calculated. Subsequently, machine learning methods were employed to reduce the dimensionality and extract connectivity features using the principal component analysis method, then a signal classification was performed (models based on Gaussian processes). Using the local patch-clamp technique in the “whole-cell” configuration, the spike activity of pyramidal neurons in the basolateral amygdala was studied. Neurons were identified by their accommodation properties. After local perfusion of the test compounds, 3 dose-response curves were obtained for: (1) U-50488 at concentrations ranging from 0.001 to 10 μM; (2) combinations of U-50488 (0.001–10 μM) and RU-1205 (10 μM); and (3) the combinations of U-50488 (0.01–10 μM) and RU-1205 (100 μM).

Results. The developed models made it possible to classify the compound RU-1205 as a “non-inhibitor” of MAPK p38 with a high probability. The results obtained were confirmed in patch-clamp experiments on acute brain slices where it was demonstrated that U-50488 statistically significantly increases the spike activity of pyramidal neurons of the basolateral amygdala (p <0.05), and RU-1205 interacts with U-50488, competitively suppressing its effect on the spike activity of neurons.

Conclusion. The findings suggest that compound RU-1205 displays properties consistent with a functional kappa agonist activity and does not have a significant effect on MAPK p38. The study demonstrates the possibility of integrating electrophysiological measurements and advanced data analysis methods for a deep understanding of drug action and underscores the potential for further research in this area.