Introduction: Rheumatoid arthritis (RА) is an immune-inflammatory disease intrinsic to up to 1.0% of the world’s population. Standard drugs for RA therapy are basic medications, glucocorticoids and non-steroid anti-inflammatory drugs, which often only ease or hinder the course of disease, not curing the patient completely. Also, on the average 20-50 % of patients are unresponsive to treatment, allergic to the prescribed drugs or find them ineffective. That is why medications with a different mechanism of action are being widely researched, some of them being antagonists of proteinase-activated receptors (PAR-2). Materials and Methods: The inflammatory process was reproduced by injecting a 2% solution of neutral formalin in a volume of 0.1 mL under the aponeurosis of the posterior left foot. A total of 84 white rats were used in the experiment. Diclofenac sodium was administered as a reference drug. Results and Discussion: An experiment on researching the impact of 5 samples of derivatives of 4.5-dihydroisoxazol-5-carboxamide on formalin oedema development among rats showed that the compound R001, compared with other substances studied, differs in the late onset of the therapeutic effect when ingested; the restoration of the foot volume to the initial level occurs only after the introduction of R005, R004 and R002. R005 to a greater extent than other compounds prevents the development of edema and has greater therapeutic efficacy than diclofenac sodium both with intragastric administration and subcutaneous injection. Conclusion: All five compounds in question showed anti-inflammatory activity, with the spectrum not so unequivocal both in qualitative and quantitative values.

Glaucoma is a disease associated with increased intraocular pressure (IOP). Of the pharmacological agents for treating glaucoma, there are drugs of the first (most effective and safe) and second-line treatment. First-line treatment includes prostaglandin analogs and beta-blockers. The currently used prostaglandin analogs (latanoprost, bimatoprost, tafluprost and travoprost) are PG F2α analogs that act through stimulation of FP receptors. They are distinguished by the optimal ratio of effectiveness and risk of side effects. They are convenient for the patient because for the therapeutic effect, it is enough to prescribe 1 time per day. As a result, it is rational to start the treatment of glaucoma with a drug in this group. In terms of pharmacoeconomics, the most affordable prostaglandin drug is latanoprost, which is generally as effective as other prostaglandin analogs. β-adrenergic blockers reduce the production of intraocular fluid, the formation of which is controlled by β1- and β2-adrenergic receptors. Therefore, non-selective β-blockers (timolol, levobunolol, metipranolol, and carteolol) have a pharmacodynamic advantage over selective β1-adrenergic antagonists (betaxolol). Conducted clinical studies of β-blockers have shown that given the cost, efficacy and safety, timolol was the most preferable treatment for glaucoma. In the presence of medical contraindications to the use of first-line drugs or to enhance their effectiveness, α2-agonists (apraclonidine and brimonidine), carbonic anhydrase inhibitors (usually local action: dorzolamide and brinzolamide), M-cholinomimetics (pilocarpine, carbachol and echothiopate), and also Rho-kinase inhibitors (ripasudil)

Rheumatoid arthritis is an immune-inflammatory disease with multifactorial etiology, affecting directly or indirectly all organs and systems of the body. Generally accepted standards of drug therapy of rheumatoid arthritis, represented by baseline anti-inflammatory drugs, glucocorticoids and non-steroidal anti-inflammatory drugs, have remained unchanged for a long time, but often they only alleviate or slow down the course of the disease, without curing the patient completely. Therefore, new pharmacologic targets for therapy are being actively investigated. A review of the literature concerning the development of innovative drugs for the treatment of rheumatoid arthritis is presented. The prospects for the development of new drugs based on inhibitors of Janus kinases, transcription factor NF-kB, mitogen-activated kinase p38, histone diethylase, phosphoinositide-3-kinase, low-molecular-weight antagonists of proteinase-activated PAR2 receptors, and anti-PAR-2-specific monoclonal antibodies are outlined.

Rheumatoid arthritis (RA) is a multifactorial incurable immune-inflammatory disease. Progression leads to joint deformation, cartilage and bone tissue destruction, and subsequent disability. The primary goal of RA pharmacotherapy is to achieve disease remission. For this purpose, several classes of drugs are used: basic anti-inflammatory drugs (DMARDs), which are a large group of synthetic and biological drugs that are combined according to their ability to influence the pathogenetic mechanisms of RA; glucocorticoids, which are recommended for use in combination with DMARDs; and non-steroidal anti-inflammatory drugs, which are used to relieve acute and chronic pain. The treatment of RA is a long-term process, and the drugs used for this condition are not always safe and not always effective, which leads to discontinuation of treatment in 20–50 % of patients. Therefore, there is a need to develop new pharmacological targets that can increase drug effectiveness and reduce drug toxicity. One promising therapeutic target is proteinase-activated receptors (PARs), particularly PAR2, whose activation contributes to the occurrence of inflammation, fibrosis, and proliferation of connective tissue. Experiments have demonstrated that inhibition of PAR2 activity prevents the development of RA pathogenesis and positively modifies the course of the disease. The search for drugs that inhibit PAR2 was carried out in the following directions: indirect blockade of PAR2 activity; creation of monoclonal antibodies; search for PAR2 inhibitors among peptide compounds; synthesis of low-molecular-weight inhibitory substances.

Introduction: Parkinson’s disease (PD) is a chronic neurodegenerative disease of the central nervous system, the pathogenesis of which is associated with the death of dopaminergic neurons of the midbrain substantia nigra. The mainstay of therapy for PD is levodopa. However, in the initial stages of PD or in case of levodopa intolerance, MAO B inhibitors are used. Purpose of the study was to determine antiparkinsonian activity of newly synthesized selective MAO-B inhibitors in vivo on the model of experimental parkinsonism in white mice. Materials and Methods: Parkinsonian syndrome in mice was modeled by systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). As the criteria for its evaluation, we used the determination of muscle rigidity severity by step length of mice and evaluation of oligokinesia severity and emotional and mental disturbances in the open field test. A total of 9 candidate compounds were studied, assigned with laboratory codes S1-S5, S9, S10, S14, and S15. Rasagiline was used as a comparison drug. Results and Discussion: Of the 9 compounds used at a dosage of 2mg/kg, the degree of rigidity was significantly reduced by compounds S1, S9, and S15; locomotor activity was restored to the level reached through rasagiline only by compound S9; the decline in exploratory activity was prevented only by S9 and to some extent by S5. Conclusion: Only compound S9 having benzenesulfonamide chemotype showed significant therapeutic potential in a model of experimental parkinsonism and only in relation to it additional studies can be planned.

Monoamine oxidase (MAO) is an FAD-dependent enzyme essential for regulating neurotransmitter levels and protecting the body from the harmful ef-fects of amines. Dysregulated MAO activity, through either overexpression or excessive activation, has been linked to diverse pathological conditions. Emerging evidence highlights MAO as a key contributor to oxidative stress, driving significant damage not only to the nervous system but also to the cardiovascular system. Additionally, MAO is implicated in tumor progression and metastasis. Targeting MAO through chemical inhibition offers promising therapeutic avenues for treating neurodegenerative disorders, cancer, heart failure, rheumatoid arthritis, multiple sclerosis, and other inflammatory diseases. Potential applications also extend to addressing migraines, dizziness, attention deficit disorders, diabetes, obesity, muscular dystrophy, and metabolic dysfunctions. This review summarizes current methodologies for assessing MAO activity and inhibition, alongside in vivo models used to study neurodegenerative diseases, providing a foundation for future therapeutic strategies. The article was prepared within the framework of the State assignment of the Yaroslavl State Pedagogical University named after K.D. Ushinsky for 2024 from the Ministry of Education of the Russian Federation on the topic "Development of a new drug for the treatment of neurodegenerative diseases based on a monoamine oxidase inhibitor" (registry entry number 720000Ф.99.1.БН62АА12000).