Research Results in Pharmacology https://rrpharmacology.ru/index.php/journal Research Results in Pharmacology is a peer-reviewed, open access, rapidly published journal covering various aspects of pharmacology. The Journal publishes articles devoted to molecular screening with the use of modern methods of proteomics, cellular technologies, results of experimental studies in modeling abnormalities in laboratory animals and clinical studies in the field of pharmacotherapy, pharmacokinetics, pharmacoepidemiology, personalized therapy, multicenter studies and evidence-based medicine. en-US rr_pharmacology@bsuedu.ru (Mikhail Pokrovskii) rr_pharmacology@bsuedu.ru (Tatyana Avtina) Wed, 16 Jul 2025 11:26:39 +0300 OJS 3.3.0.13 http://blogs.law.harvard.edu/tech/rss 60 Anxiolytic, antidepressant and analgesic activities of novel derivatives of 1-(3-phenylpyrrol-2-yl)-1,3-dihydro-2H-benzimidazol-2-one https://rrpharmacology.ru/index.php/journal/article/view/802 <p style="font-weight: 400;"><strong>Introduction</strong>: Benzimidazole (1,3-benzodiazole) derivatives hold an important place in the field of medicinal chemistry, since they have a wide spectrum of pharmacological activity, as well as high variability of the mechanisms of action: GABA-, serotonin-, dopamine-, adrenaline-, angiotensin-, adenosine-, and glutamatergic. In view of the diversity of the ways of influence of benzimidazole derivatives on neurotransmitter systems, as well as the pharmacological effects of these compounds, the synthesis of highly effective neurotropic drugs with an improved safety profile on their basis is ofinterest for study. <strong>The aim of this study </strong>was to investigate the neuropsychotropic potential of new derivatives of 1-(3-phenylpyrrol-2-yl)-1,3-dihydro-2H-benzimidazole-2-one <em>in vivo</em>.</p> <p style="font-weight: 400;"><strong>Materials and Methods</strong>: The study was conducted on 258 white outbred male mice weighing 25-30 g. The work was carried out in several stages. At the first stage, the safety of the compounds was studied by <em>in silico</em> methods using the PASS-online program with a preliminary calculation of LD<sub>50</sub>. At the second stage, animals were tested under the influence of the compounds in the Open Field and Light-Dark Box tests. <a href="https://pubchem.ncbi.nlm.nih.gov/compound/Etifoxine">Etifoxine</a> (50 mg/kg) and <a href="https://pubchem.ncbi.nlm.nih.gov/compound/Phenazepam">phenazepam</a> (0.1 mg/kg) were chosen as comparison drugs. At the third stage, the behavior of rodents was studied in Porsolt test, with <a href="https://pubchem.ncbi.nlm.nih.gov/compound/Amitriptyline">amitriptyline</a> (10 mg/kg) and <a href="https://pubchem.ncbi.nlm.nih.gov/compound/Fluoxetine">fluoxetine</a> (10 mg/kg) used as reference drugs. At the fourth stage, the analgesic properties of the compounds were assessed in the Tail-flick and Hot Plate tests in comparison with <a href="https://pubchem.ncbi.nlm.nih.gov/compound/Morphine">morphine</a> (5 mg/kg).</p> <p style="font-weight: 400;"><strong>Results and Discussion</strong>: Based on the obtained results, it can be noted that the phenyl-containing compound CHS-Bi-46 has anxiolytic activity with an antidepressant component. Compounds containing pyridin-3-yl (CHS-Bi-48) and 2-bromophenyl (CHS-Bi-52) are characterized by antidepressant properties, and CHS-Bi-52 also showed a weak analgesic effect in the Hot plate test. For the substance with a pyridin-4-yl fragment CHS-Bi-47, no significant effects were registered according to the results of the tests, but this substance may have other pharmacological activities. 4-Chlorophenyl substance coded CHS-Bi-50 exhibits antinociceptive activity at the spinal level, which is equal to the reference drug <a href="https://pubchem.ncbi.nlm.nih.gov/compound/Morphine">morphine</a> at a dose of 5 mg/kg. The 4-bromophenyl-containing compound CHS-Bi-51 is characterized by a moderate combined spinal and supraspinal analgesic property. It can be noted that the most suitable structure for the manifestation of anxiolytic and antidepressant properties of compounds is the presence of a phenyl substituent in the 5 position of the pyrrole ring, and the severity of the analgesic effects of substances is affected by the presence of Cl atoms in the phenyl radical in position 4 for spinal effects and Br – in positions 2 and 4 for supraspinal effects.</p> <p style="font-weight: 400;"><strong>Conclusion</strong>: The obtained data indicate the prospects of further study of 1-(3-phenylpyrrol-2-yl)-1,3-dihydro-2<em>H</em>-benzimidazole-2-one derivatives in order to search for substances with neuropsychotropic activity.</p> Maria О. Maltseva, Kristina I. Adzhienko, Raul I. Musaev, Alexander A. Spasov, Vahid A. Mamedov, Natalia A. Zhukova, Sevil V. Mamedova, Nalatalia V. Eliseeva, Karina R. Magomedova, Dmitriy V. Maltsev Copyright (c) 2025 Maltseva MO, Adzhienko KI, Musaev RI, Spasov AA, Mamedov VA, Zhukova NA, Mamedova S.V.K., Eliseeva NV, Magomedova KR, Maltsev DV https://creativecommons.org/licenses/by/4.0/legalcode.en https://rrpharmacology.ru/index.php/journal/article/view/802 Sat, 27 Sep 2025 00:00:00 +0300 Adherence to dual antiplatelet therapy among outpatients after acute myocardial infarction in primary care https://rrpharmacology.ru/index.php/journal/article/view/752 <p style="font-weight: 400;"><strong>Introduction:</strong> The efficacy outcomes of dual antiplatelet therapy (DAPT) observed in randomized controlled trials are often not replicated in real-world post-myocardial infarction (MI) patients due to suboptimal adherence to prescribed pharmacotherapy. This study aimed to assess DAPT adherence in outpatients after MI and evaluate its association with risk of major adverse cardiovascular events (MACE).</p> <p style="font-weight: 400;"><strong>Material and methods:</strong> This retrospective pharmacoepidemiologic study included 276 patients who experienced AMI between January 1, 2021, and December 31, 2023, based on electronic medical data. Adherence was measured using proportion of days covered (PDC) metric. Kaplan-Meier curves were constructed to evaluate the impact of DAPT adherence on the incidence of MACE over a 12-month period.</p> <p style="font-weight: 400;"><strong>Results:</strong> Patients primarily received ASA 100 mg (91.3%) in combination with P2Y12 inhibitor <a href="https://pubchem.ncbi.nlm.nih.gov/compound/Ticagrelor">ticagrelor</a> (68.5%). The proportion of patients fully adherent to DAPT (PDC≥80% for both components) over 12 months was only 46.4%, with a significant decline from 60.9% to 42.0% between first and second half-year periods (p&lt;0.001). Adherence to P2Y12 inhibitors was significantly higher compared to ASA (87.8±18.9% vs. 73.6±27.5%; p&lt;0.001), largely due to high adherence to <a href="https://pubchem.ncbi.nlm.nih.gov/compound/Ticagrelor">ticagrelor</a> (PDC=92.5±12.8%). Post-MI patients fully adherent to DAPT had a lower probability of MACE compared to non-adherent (p=0.047). The protective effect of optimal adherence, adjusted for patient comorbidity, was also assessed using Cox regression, which demonstrated a 2% reduction in MACE risk for every 1% increase in PDC (p&lt;0.05).</p> <p style="font-weight: 400;"><strong>Conclusion:</strong> Higher adherence to DAPT following MI was associated with lower risk of MACE. However, adherence declined over time, underscoring the necessity of enhancing medication adherence in post-MI outpatients.</p> Sergey B. Fitilev, Alexander V. Vozzhaev, Irina I. Shkrebniova, Dmitry A. Klyuev, Anna O. Ovaeva, Darya K. Barsukova Copyright (c) 2025 Sergey B. Fitilev, Alexander V. Vozzhaev, Irina I. Shkrebniova, Dmitry A. Klyuev, Anna O. Ovaeva, Darya K. Barsukova https://creativecommons.org/licenses/by/4.0/legalcode.en https://rrpharmacology.ru/index.php/journal/article/view/752 Sat, 27 Sep 2025 00:00:00 +0300 Orthogonal approach and critical quality attributes for gene and cell therapy products https://rrpharmacology.ru/index.php/journal/article/view/738 <div> <p class="1"><strong><span lang="EN-US">Introduction:</span></strong><span lang="EN-US"> Gene and cell therapy (GCT) products are revolutionizing medicine because they are made up of unique biological components like genetic material, viral vectors, and viable cells. However, their complexity necessitates rigorous quality control strategies to ensure efficacy, safety, and batch consistency. This manuscript explores the application of an orthogonal approach – employing multiple independent methods – to assess critical quality attributes, such as identity, potency, and purity of GCT products.</span></p> </div> <div> <p class="1"><strong><span lang="EN-US">Materials and Methods: </span></strong><span lang="EN-US">To achieve the aim of our work, we analyzed 15 GCT products for 11 different types of diseases and reports of multiple regulatory agencies.</span></p> </div> <div> <p class="1"><strong><span lang="EN-US">Results:</span></strong><span lang="EN-US"> For cell-based therapies, identity is confirmed through genotypic, phenotypic, and morphological analyses, while potency is evaluated using functional assays tailored to the product’s mechanism of action, such as cell viability, differentiation status, or cytokine secretion. Viral vector-based therapies require characterization of structural integrity, transgene expression, and the ratio of full to empty capsids, employing techniques like dynamic light scattering (DLS), PCR, and ELISA.</span></p> </div> <div> <p class="1"><strong><span lang="EN-US">Conclusion:</span></strong><span lang="EN-US"> The paper highlights regulatory recommendations from the FDA, EMA, and WHO, emphasizing the need for validated assays during product release and stability testing. Case studies, including CAR-T cells and AAV-based therapies, illustrate the practical implementation of orthogonal methods. Challenges such as assay variability and the need for clinical correlation are discussed, underscoring the importance of assay development early in the product lifecycle. By integrating diverse analytical techniques, the orthogonal approach ensures comprehensive product characterization facilitating the translation of GCTs from research to clinical application.</span></p> </div> Ekaterina V. Melnikova, Marina A. Vodyakova, Nikita S. Pokrovsky, Vadim A. Merkulov Copyright (c) 2025 Melnikova EV, Vodyakova MA, Pokrovsky NS, Merkulov VA https://creativecommons.org/licenses/by/4.0/legalcode.en https://rrpharmacology.ru/index.php/journal/article/view/738 Tue, 30 Sep 2025 00:00:00 +0300 Cytotoxicity study of transdermal desloratadine delivery system on murine melanoma and human dermal fibroblast cell cultures https://rrpharmacology.ru/index.php/journal/article/view/731 <p>treat and prevent allergic conditions, reducing the adverse effects associated with oral administration.</p> <p>Materials and Methods: We evaluated the cytotoxicity of the transdermal <a href="https://pubchem.ncbi.nlm.nih.gov/compound/Desloratadine">desloratadine</a>delivery system in micellar and ionic forms on murine melanoma and human dermal fibroblast cell cultures using the MTT assay and resazurin live cell assay.</p> <p>Results: The results of the MTT assay demonstrated that <a href="https://pubchem.ncbi.nlm.nih.gov/compound/Desloratadine">desloratadine</a> in micellar and ionic forms had a more pronounced cytotoxic effect on murine melanoma cells than on human dermal fibroblasts. The transdermal system had no effect on cell viability. <a href="https://pubchem.ncbi.nlm.nih.gov/compound/Desloratadine">Desloratadine</a> in micellar or ionic form reduced cell viability: the survival rate of murine melanoma cells was below 50%, while when incubated with the transdermal system, the viability of human dermal fibroblasts was above 70%, indicating no toxicity.</p> <p>Discussion: The polyvinylpyrrolidone-based transdermal system is not cytotoxic, but the active ingredient, <a href="https://pubchem.ncbi.nlm.nih.gov/compound/Desloratadine">desloratadine</a>, features antiproliferative activity, to a greater extent, in relation to tumor cells.</p> <p>Conclusion: The obtained results demonstrated the cytotoxic effect of micellar and ionic <a href="https://pubchem.ncbi.nlm.nih.gov/compound/Desloratadine">desloratadine</a> on the tumor culture of murine melanoma and the biocompatibility of the transdermal <a href="https://pubchem.ncbi.nlm.nih.gov/compound/Desloratadine">desloratadine</a> delivery system with human dermal fibroblasts.</p> Ekaterina P. Brodovskaya , Aminah M. Al-Hajj Ayub, Dmitry O. Semikov, Valentine P. Ageev, Andrey V. Zaborovskiy, Larisa A. Tararina, Dina V. Yunina, Sergey A. Litvinov, Izabella M. Dadaeva, Natalia V. Kheladze, Dmitriy N. Andreev, Elena G. Lobanova, Nikolay A. Pyataev Copyright (c) 2025 Brodovskaya EP, Al-Hajj Ayub AM, Semikov DO, Ageev VP, Zaborovskiy AV, Tararina LA, Yunina DV, Litvinov SA, Dadaeva IM, Kheladze NV, Andreev DN, Lobanova EG, Pyataev NA (2025) Cytotoxicity study of transdermal desloratadine delivery system on muri https://creativecommons.org/licenses/by/4.0/legalcode.en https://rrpharmacology.ru/index.php/journal/article/view/731 Thu, 26 Jun 2025 00:00:00 +0300 Comparison of CD-1 and ICR mouse strains for impulsivity in the enriched cross-maze test: Effects of atomoxetine https://rrpharmacology.ru/index.php/journal/article/view/724 <p style="font-weight: 400;"><strong>Introduction:</strong> Attention deficit hyperactivity disorder (ADHD) in children and adults is a neuropsychiatric condition that is characterized by difficulty sustaining attention and behavioral impulsivity. It is one of the problems of modern medicine requiring development of appropriate treatments and valid animal models. Previously, we have developed a model of the enriched cross-maze test suitable for express-evaluation of attention deficiency in rodents. Recently, we have also revealed that while employing spontaneously hypertensive rats it is possible to estimate impulsivity indices in the test. The present study is aimed at evaluation of the impulsivity indicators in the enriched cross-maze test employing mice of outbred CD-1 and ICR strains, belonging to different breeding cores.</p> <p style="font-weight: 400;"><strong>Materials and Method:</strong> Adult male mice of the both outbred CD-1 (n=199) and ICR (n=148) strains were used in the study. <a href="https://pubchem.ncbi.nlm.nih.gov/compound/Atomoxetine">Atomoxetine</a> (3 mg/kg) as the drug of choice for ADHD was administered intraperitoneally once daily for 6 consecutive days.</p> <p style="font-weight: 400;"><strong>Results and Discussion</strong>: Frequency distribution of the impulsivity index obtained from mice of both strains had a clear bimodal shape that statistically significantly differed from the normal distribution. The outcome indicates existence of subpopulations of individuals with high and low impulsivity. In inattentive mice, the subchronic <a href="https://pubchem.ncbi.nlm.nih.gov/compound/Atomoxetine">atomoxetine</a> administration selectively improved impulsivity indicators in the second enriched cross-maze test.</p> <p style="font-weight: 400;"><strong>Conclusion</strong>: The enriched cross-maze test may be useful in neurobiology studies of ADHD and for screening new drug candidates for the ADHD treatment.</p> <h1> </h1> <p> </p> Ramiz M. Salimov, Natalia А. Sukhorukova, Georgy I. Kovalev Copyright (c) 2025 Salimov RM, Sukhorukova NA, Kovalev GI https://creativecommons.org/licenses/by/4.0/legalcode.en https://rrpharmacology.ru/index.php/journal/article/view/724 Sat, 27 Sep 2025 00:00:00 +0300 The effect of acute swimming stress, corticosterone, dexamethasone, and fludrocortisone on anxiety-like behavior in mice https://rrpharmacology.ru/index.php/journal/article/view/725 <p style="font-weight: 400;"><strong>Introduction: </strong>Acute swimming stress (ASS) exerts a biphasic effect on anxiety-like behavior (ALB) in mice, inducing an enhancement and a subsequent decrease in ALB 1 h and 24 h after exposure, respectively. Presumably, this effect may be caused by the activation of mineralocorticoid and glucocorticoid receptors, both during the immediate response to acute stress and after its termination at the phase of adaptive changes. <strong>Aim of the Research</strong>: Comparative study of the effects of acute swimming stress, <a href="https://pubchem.ncbi.nlm.nih.gov/compound/Corticosterone">corticosterone</a>, <a href="https://pubchem.ncbi.nlm.nih.gov/compound/Dexamethasone">dexamethasone</a>, and <a href="https://pubchem.ncbi.nlm.nih.gov/compound/Fludrocortisone">fludrocortisone</a> on ALB in mice 1 h and 24 h after stress exposure or administration of the studied substances.</p> <p style="font-weight: 400;"><strong>Materials and Methods:</strong> To model ASS in adult male ICR mice, the forced swimming test (FST) was employed. ALB was assessed in mice in the open field test 1 h and 24 h after FST or systemic administration of <a href="https://pubchem.ncbi.nlm.nih.gov/compound/Corticosterone">corticosterone</a> (20 mg/kg), <a href="https://pubchem.ncbi.nlm.nih.gov/compound/Dexamethasone">dexamethasone</a> (10 mg/kg), and <a href="https://pubchem.ncbi.nlm.nih.gov/compound/Fludrocortisone">fludrocortisone</a> (0.04 mg/kg).</p> <p style="font-weight: 400;"><strong>Results</strong>: Central activity and anxiety index were increased 1 h after exposure to FST, while an increase in the anxiety index was observed 24 h after exposure to FST in the open field test compared to the non-stressed mice. <a href="https://pubchem.ncbi.nlm.nih.gov/compound/Corticosterone">Corticosterone</a>, <a href="https://pubchem.ncbi.nlm.nih.gov/compound/Dexamethasone">dexamethasone</a>, and <a href="https://pubchem.ncbi.nlm.nih.gov/compound/Fludrocortisone">fludrocortisone</a>decreased central activity and anxiety index 1 h after the administration, compared to the control group. However, <a href="https://pubchem.ncbi.nlm.nih.gov/compound/Fludrocortisone">fludrocortisone</a> decreased central activity and total locomotor activity 24 h after administration compared to the control group.</p> <p style="font-weight: 400;"><strong>Conclusion</strong>: A similar pattern of enhancement of anxiety-like behavior was observed in mice 1 h after FST or the administration of <a href="https://pubchem.ncbi.nlm.nih.gov/compound/Corticosterone">corticosterone</a> (single dose 20 mg/kg, i.p.), <a href="https://pubchem.ncbi.nlm.nih.gov/compound/Dexamethasone">dexamethasone</a>(single dose 10 mg/kg, i.p.), and <a href="https://pubchem.ncbi.nlm.nih.gov/compound/Fludrocortisone">fludrocortisone</a> (single dose 0.04 mg/kg, i.p.). Nonetheless, 24 h after exposure to stress or administration of the studied substances, FST decreased ALB, <a href="https://pubchem.ncbi.nlm.nih.gov/compound/Fludrocortisone">fludrocortisone</a> enhanced ALB, while <a href="https://pubchem.ncbi.nlm.nih.gov/compound/Corticosterone">corticosterone</a> and <a href="https://pubchem.ncbi.nlm.nih.gov/compound/Dexamethasone">dexamethasone</a> showed no effect on ALB in mice 24 h after exposure to stress or administration of the studied substances.</p> Nikita V. Kudryashov, Alexander A. Gorbunov, Sergey E. Mironov, Dmitriy A. Tikhonov, Andrey A. Nedorubov; Olga Yu. Arshinova; Maria A. Simukhina, Vera N. Busol, Vladimir P. Fisenko Copyright (c) 2025 Kudryashov NV, Gorbunov AA, Mironov SE, Tikhonov DA, Nedorubov AA, Arshinova OYu, Simukhina MA, Busol VN, Fisenko VP https://creativecommons.org/licenses/by/4.0/legalcode.en https://rrpharmacology.ru/index.php/journal/article/view/725 Mon, 23 Jun 2025 00:00:00 +0300 Correction of protein and lipid spectra of erythrocyte membranes as a pathogenetic supplement to the therapy of coronary heart disease https://rrpharmacology.ru/index.php/journal/article/view/718 <p style="font-weight: 400;"><strong>Introduction:</strong> Coronary heart disease is currently a pressing problem in the medical and scientific community. The hemic component, which is a disruption of the ability of red blood cells to effectively exchange gases, is of great importance in ischemic myocardial damage. Oxidative stress, through functional and structural changes in red blood cells, can significantly impair the efficiency of oxygen delivery to tissues.</p> <p style="font-weight: 400;"><strong>Materials and Methods:</strong> In this clinical study, 80 patients suffering from coronary heart disease (stable angina pectoris functional class II-III) were selected. They were divided into two groups, one of which received traditional treatment, and the other – traditional treatment in combination with <a href="https://pubchem.ncbi.nlm.nih.gov/compound/129761399">Mexicor</a>. Before the start of taking the drugs and 11 days after the start of therapy, the clinical condition of the patients, bicycle ergometry indicators and the values of protein and lipid spectra of erythrocyte membranes were assessed.</p> <p style="font-weight: 400;"><strong>Results:</strong> Addition of <a href="https://pubchem.ncbi.nlm.nih.gov/compound/129761399">Mexicor</a>, a drug with antioxidant and endothelioprotective properties, to the classical approach to therapy resulted in correction of various clinical parameters by values from 11% to 58.82%; bicycle ergometry – from 20.29% to 70.31%; protein spectrum of erythrocyte membranes – from 3.08% to 75.41%; and lipid spectrum – from 8.67% to 35.83%. Moreover, most of the studied parameters statistically significantly differed from those both in the control group and the traditional treatment group.</p> <p style="font-weight: 400;"><strong>Conclusion:</strong> The combination of traditional treatment with single daily intravenous injections of 5 mL of <a href="https://pubchem.ncbi.nlm.nih.gov/compound/129761399">Mexicor</a>(<a href="https://pubchem.ncbi.nlm.nih.gov/compound/129761399">ethylmethylhydroxypyridine succinate</a> 50 mg/mL), made it possible not only to improve the clinical course and functional indicators, but also to positively influence the pathogenetic causes of ischemia development through significant, statistically reliable correction of the indicators of the protein and lipid spectrum of red blood cell membranes.</p> Svetlana G. Dorofeeva, Eugenia N. Konoplya, Oksana V. Mansimova Copyright (c) 2025 Dorofeeva SG, Konoplya EN, Mansimova OV https://creativecommons.org/licenses/by/4.0/legalcode.en https://rrpharmacology.ru/index.php/journal/article/view/718 Tue, 01 Jul 2025 00:00:00 +0300 Cardiotropic medicinal products of plant origin. Prospects for use in modern clinical practice https://rrpharmacology.ru/index.php/journal/article/view/549 <p style="font-weight: 400;"><strong>Introduction: </strong>The aim of the research was to study the current state of use and improvement of the prospects for the using cardiological medicinal products obtained on the basis of medicinal plant raw materials.</p> <p style="font-weight: 400;"><strong>Materials and Methods:</strong> The work used content analysis, monitoring of scientific articles using the databases PubMed, Scopus, Google Scholar, ResearchGate, analysis of the nomenclature of the State Register of Medicines of the Russian Federation (2024) and the Register of Medicines of Russia (2024).</p> <p style="font-weight: 400;"> <strong>Results and Discussion: </strong>The study revealed that diseases of the cardiovascular system are some of the most common causes of death among the population, with at least 37.7 million people suffering from varying degrees of heart failure alone. Despite the constant growth of the range of medicines for the treatment of cardiovascular diseases, medicinal plants and preparations based on them, which are more often used in complex therapy, still play an important role in their therapy. In this review, we consider drugs derived from medicinal plant raw materials used for the treatment of heart failure and arrhythmia of various etiologies, as the most serious cardiovascular pathologies.</p> <p style="font-weight: 400;"><strong>Conclusion:</strong> Preparations based on herbal remedies with cardiotropic and antiarrhythmic effects are relevant in the treatment of cardiovascular diseases. Cardiotropic action is characteristic of the group of cardiac glycosides, and antiarrhythmic activity is more pronounced in alkaloids and flavonoid substances. Taking into account the prospects for the use of herbal preparations with cardiotropic effects in the complex therapy of cardiovascular diseases, an important and unsolved problem today remains the problem of their interaction with other drugs, which in the future can be solved by creating artificial intelligence programs that contribute to the formation of optimal prescriptions for a particular patient.</p> Nadezhda V. Nesterova, Natalia D. Bunyatyan, Irina A. Samylina, Vladimir A. Evteev Copyright (c) 2025 Nadezhda V. Nesterova, Natalia D. Bunatyan, Irina A. Samylina, Vladimir A. Evteev https://creativecommons.org/licenses/by/4.0/legalcode.en https://rrpharmacology.ru/index.php/journal/article/view/549 Sun, 30 Mar 2025 00:00:00 +0300 Assessment of physiological parameters in the application of a double adeno-associated virus 9 with a codon-optimized DYSF gene for limb girdle muscular dystrophy type R2 https://rrpharmacology.ru/index.php/journal/article/view/642 <p style="font-weight: 400;"><strong>Introduction:</strong> Gene therapy for Myoshi myopathy is extremely relevant, as it may become the first pathogenetic treatment for dysferlinopathy. <strong>The aim </strong>of this study was to study the efficacy and safety of the use of a genetic construct, the AAV9-DYSF-DV3’ virus, for the treatment of limb girdle muscular dystrophy LGMD) type R2.</p> <p style="font-weight: 400;"><strong>Materials and Methods: </strong>Mouse models of limb girdle muscular dystrophy type R2 В6.А-Dysf<sup>prmd</sup>/GeneJ were used to study the effectiveness of AAV9.DYSF drug and the corresponding C57BL/6J controls were used. During the study, muscle activity was determined on the basis of the following tests: “Grip test”, “Holding an animal on a slippery surface of a vertical rod”, “Forced swimming with a load”, and ”Wire hanging”. In the course of acute and subchronic toxicity, hematological and biochemical blood tests of the rats, histological analysis and ”Open field” behavioral testing were performed.</p> <p style="font-weight: 400;"><strong>Results and Discussion: </strong>In this study, for the first time, a comprehensive investigation of the effectiveness of gene therapy using the two-vector system of adeno-associated AAV9-DYSF-DV3’ virus with overlapping DYSF cDNA sequences was conducted in a mouse model of limb girdle muscular dystrophy type 2 R.</p> <p style="font-weight: 400;"><strong>Conclusion: </strong>During the testing of the drug’s effectiveness, it was discovered that drug AAV9.DYSF showed the best effectiveness in mice with the absence of the protein dysferlin in behavioral testing at the maximum dose (5*10<sup>12</sup>) with a double intramuscular injection. In the “Grip test”, the index in В6.А-Dysf<sup>prmd</sup>/GeneJ mice increased by 29% (p=0.0026) relative to that in the K-group. In the tests “Forced swimming with a load”, ”Wire hanging”, and ”Holding an animal on a slippery surface of a vertical rod”, the indicators also improved by 80% (p=0.0019), 104.8% (p=0.001) and 20% (p=0.025), respectively, relative to those of the negative control. During acute and subchronic toxicity, the administration of the drug to animals does not cause death or intoxication.</p> Elеna V. Kuzubova, Alexandra I. Radchenko, Andrey А. Manuylov, Ariana M. Korokina, Natalia V. Koroleva, Ivan A. Yakovlev, Arthur A. Isaev, Roman V. Deev, Mikhail V. Korokin Copyright (c) 2025 Kuzubova EV, Radchenko AI, Manuylov AA, Korokina AM, Koroleva NV, Yakovlev IA, Isaev AA, Deev RV, Korokin MV https://creativecommons.org/licenses/by/4.0/legalcode.en https://rrpharmacology.ru/index.php/journal/article/view/642 Mon, 23 Jun 2025 00:00:00 +0300 Nonclassical cardiovascular effects of imidazoline receptor agonists https://rrpharmacology.ru/index.php/journal/article/view/640 <p style="font-weight: 400;"><strong>Introduction:</strong> Imidazoline receptors are a group of metabotropic receptors whose activation is associated with changes in a number of functional parameters, including hemodynamics (lowering blood pressure (BP), negative chrono-and inotropic effects), metabolic metabolism (reducing insulin resistance, increasing high-density lipoproteins (HDL) levels) and hemorheology (antiplatelet activity). In addition, the spectrum of molecular pharmacological effects of imidazoline receptor (IR) agonists includes anti-inflammatory, antioxidant, and antifibrinolytic activities.</p> <p style="font-weight: 400;"><strong>Materials and Methods</strong>: Literature sources were searched using PubMed and Google Scholar databases, including such article types as meta-analysis, randomized controlled trial, and review. The inclusion criteria were full availability of data, scientific significance, and relevance of research.</p> <p style="font-weight: 400;"><strong>Results and Discussion:</strong> Experimental studies in animals revealed such effects of agonists IR as a decrease in the degree of left ventricular hypertrophy (LVH) and interleukin expression. The experience of using agonists IR therapy in clinical practice has revealed its effectiveness in the treatment of patients with chronic heart failure (CHF) II-IIIof NYHA class II-III NYHA with an ejection fraction of less than 40%, arterial hypertension (AH) and microalbuminuria.</p> <p style="font-weight: 400;"><strong>Conclusions:</strong> In general, the totality of data available to date indicates a high expediency of including imidazoline receptors in the repertoire of pharmacological targets, the impact on which can affect not only soft, but also hard endpoints in the treatment of cardiovascular pathology.</p> Yulia V. Stepenko, Olesya V. Shcheblykina, Anna A. Peresypkina, Veronika S. Shmigerova, Yomna Y.O.M. Akhmed , Tatiana A. Denisyuk, Anton P. Danilenko; Nikita S. Lyapkalov; Elena A. Shmykova, Lyudmila M. Danilenko Copyright (c) 2025 Stepenko YuV, Shcheblykina OV, Peresypkina AA, Shmigerova VS, Akhmed YYOM, Denisyuk TA, Danilenko AP, Lyapkalov NS, Shmykova EA, Danilenko LM https://creativecommons.org/licenses/by/4.0/legalcode.en https://rrpharmacology.ru/index.php/journal/article/view/640 Tue, 30 Sep 2025 00:00:00 +0300