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  Subjects -> PHARMACY AND PHARMACOLOGY (Total: 575 journals)
Showing 401 - 253 of 253 Journals sorted alphabetically
Microbial Drug Resistance     Hybrid Journal   (Followers: 3)
Molecular Informatics     Hybrid Journal   (Followers: 5)
Molecular Pharmacology     Hybrid Journal   (Followers: 2)
Molekul     Open Access   (Followers: 1)
Natural Product Communications     Open Access  
Nature Reviews Drug Discovery     Full-text available via subscription   (Followers: 318)
Naunyn-Schmiedeberg's Archives of Pharmacology     Hybrid Journal  
NeuroMolecular Medicine     Hybrid Journal  
Neuropharmacology     Hybrid Journal   (Followers: 6)
Neuropsychopharmacology     Hybrid Journal   (Followers: 18)
Neuropsychopharmacology Reports     Open Access  
Nigerian Journal of Natural Products and Medicine     Full-text available via subscription  
OA Drug Design & Delivery     Open Access  
OA Medical Hypothesis     Open Access  
Obesity Facts     Open Access   (Followers: 8)
Open Pharmacoeconomics & Health Economics Journal     Open Access  
Open Pharmacology Journal     Open Access  
OpenNano     Open Access   (Followers: 1)
Orbital - The Electronic Journal of Chemistry     Open Access   (Followers: 1)
Oriental Pharmacy and Experimental Medicine     Partially Free   (Followers: 2)
Pain and Therapy     Open Access   (Followers: 3)
Particulate Science and Technology: An International Journal     Hybrid Journal   (Followers: 1)
PDA Journal of Pharmaceutical Science and Technology     Full-text available via subscription   (Followers: 36)
Pediatric Drugs     Full-text available via subscription   (Followers: 4)
Pediatric Pharmacology     Open Access   (Followers: 1)
Pharmaceutica Analytica Acta     Open Access  
Pharmaceutical Biology     Open Access  
Pharmaceutical Care-La Farmacoterapia     Open Access  
Pharmaceutical Chemistry Journal     Hybrid Journal  
Pharmaceutical Development and Technology     Hybrid Journal   (Followers: 21)
Pharmaceutical Executive     Full-text available via subscription   (Followers: 6)
Pharmaceutical Fronts     Open Access   (Followers: 6)
Pharmaceutical Historian     Open Access  
Pharmaceutical Journal     Free   (Followers: 8)
Pharmaceutical Journal of Sri Lanka     Open Access  
Pharmaceutical Medicine     Full-text available via subscription   (Followers: 4)
Pharmaceutical Nanotechnology     Hybrid Journal  
Pharmaceutical Patent Analyst     Full-text available via subscription   (Followers: 3)
Pharmaceutical Research     Hybrid Journal   (Followers: 97)
Pharmaceutical Statistics     Hybrid Journal   (Followers: 16)
Pharmaceutical Technology     Full-text available via subscription   (Followers: 6)
Pharmaceuticals     Open Access   (Followers: 4)
Pharmacia     Open Access  
PharmacoEconomics     Full-text available via subscription   (Followers: 26)
PharmacoEconomics & Outcomes News     Full-text available via subscription   (Followers: 4)
PharmacoEconomics German Research Articles     Full-text available via subscription  
PharmacoEconomics Spanish Research Articles     Hybrid Journal   (Followers: 1)
Pharmacoepidemiology and Drug Safety     Hybrid Journal   (Followers: 34)
Pharmacogenetics and Genomics     Hybrid Journal   (Followers: 1)
Pharmacogenomics     Hybrid Journal   (Followers: 7)
Pharmacogenomics and Personalized Medicine     Open Access   (Followers: 2)
Pharmacogenomics Journal     Hybrid Journal   (Followers: 5)
Pharmacognosy Communications     Partially Free  
Pharmacognosy Magazine     Open Access   (Followers: 2)
Pharmacognosy Research     Open Access   (Followers: 2)
Pharmacological Reports     Hybrid Journal  
Pharmacological Research     Hybrid Journal   (Followers: 1)
Pharmacological Research - Modern Chinese Medicine     Open Access  
Pharmacological Reviews     Hybrid Journal   (Followers: 2)
Pharmacology     Full-text available via subscription  
Pharmacology & Therapeutics     Hybrid Journal   (Followers: 3)
Pharmacology & Pharmacy     Open Access   (Followers: 1)
Pharmacology Biochemistry and Behavior     Hybrid Journal   (Followers: 2)
Pharmacology Research & Perspectives     Open Access  
Pharmacon : Jurnal Farmasi Indonesia     Open Access  
Pharmacopsychiatry     Hybrid Journal   (Followers: 3)
Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy     Hybrid Journal   (Followers: 38)
Pharmactuel     Open Access   (Followers: 1)
Pharmacy     Open Access   (Followers: 4)
Pharmacy & Pharmacology     Open Access  
Pharmacy Education     Full-text available via subscription   (Followers: 11)
Pharmacy Practice (Internet)     Open Access   (Followers: 8)
Pharmakon : Arzneimittel in Wissenschaft und Praxis     Full-text available via subscription   (Followers: 1)
PharmaNutrition     Hybrid Journal   (Followers: 3)
PharmaTutor     Open Access  
Pharmazeutische Industrie     Full-text available via subscription   (Followers: 11)
Pharmazeutische Zeitung     Full-text available via subscription   (Followers: 15)
Pharmazie in Unserer Zeit (Pharmuz)     Hybrid Journal   (Followers: 18)
Physiology International     Full-text available via subscription   (Followers: 3)
Plant Products Research Journal     Full-text available via subscription  
Planta Medica     Hybrid Journal   (Followers: 4)
Planta Medica International Open     Open Access  
Prescriber     Hybrid Journal   (Followers: 9)
Progress in Neuro-Psychopharmacology and Biological Psychiatry     Hybrid Journal   (Followers: 8)
Psychiatry and Clinical Psychopharmacology     Open Access   (Followers: 1)
Psychopharmacology     Hybrid Journal   (Followers: 16)
Pulmonary Pharmacology & Therapeutics     Hybrid Journal   (Followers: 2)
PZ Prisma : Materialien zur Fort- und Weiterbildung     Full-text available via subscription  
Redox Report     Open Access  
Regulatory Mechanisms in Biosystems     Open Access   (Followers: 1)
Regulatory Toxicology and Pharmacology     Hybrid Journal   (Followers: 41)
Research & Reviews : A Journal of Drug Design & Discovery     Full-text available via subscription  
Research & Reviews : A Journal of Pharmaceutical Science     Full-text available via subscription  
Research & Reviews : A Journal of Pharmacognosy     Full-text available via subscription  
Research & Reviews : A Journal of Pharmacology     Full-text available via subscription   (Followers: 1)
Research in Pharmaceutical Sciences     Open Access   (Followers: 3)
Research in Social and Administrative Pharmacy     Hybrid Journal   (Followers: 3)
Research Journal of Pharmacognosy     Open Access  
Research Results in Pharmacology     Open Access  
Reviews of Physiology, Biochemistry and Pharmacology     Hybrid Journal   (Followers: 4)
Reviews on Clinical Pharmacology and Drug Therapy     Full-text available via subscription  
Revista Colombiana de Ciencias Químico-Farmacéuticas     Open Access  
Revista Cubana de Plantas Medicinales     Open Access   (Followers: 1)
Revista de Ciências Farmacêuticas Básica e Aplicada     Open Access  
Revista Mexicana de Ciencias Farmaceuticas     Open Access  
Revue de Médecine et de Pharmacie     Full-text available via subscription  
Safety and Risk of Pharmacotherapy     Open Access   (Followers: 1)
Saudi Pharmaceutical Journal     Open Access  
Scandinavian Journal of Clinical and Laboratory Investigation     Hybrid Journal   (Followers: 8)
Scientia Pharmaceutica     Open Access  
Seminars in Hematology     Hybrid Journal   (Followers: 12)
Seminars in Oncology Nursing     Full-text available via subscription   (Followers: 10)
Separation Science plus (SSC plus)     Hybrid Journal  
Side Effects of Drugs Annual     Full-text available via subscription   (Followers: 2)
Skin Pharmacology and Physiology     Full-text available via subscription   (Followers: 6)
Substance Abuse : Research and Treatment     Open Access   (Followers: 5)
Suchttherapie     Hybrid Journal   (Followers: 1)
Sustainable Chemistry and Pharmacy     Full-text available via subscription   (Followers: 1)
Synfacts     Hybrid Journal   (Followers: 5)
SynOpen     Open Access  
The Botulinum J.     Hybrid Journal  
The Brown University Psychopharmacology Update     Hybrid Journal   (Followers: 2)
The Medical Letter     Full-text available via subscription   (Followers: 18)
The Pink Sheet     Full-text available via subscription   (Followers: 12)
The Pink Sheet Daily     Full-text available via subscription   (Followers: 5)
Therapeutic Advances in Drug Safety     Open Access   (Followers: 3)
Therapeutic Advances in Psychopharmacology     Open Access   (Followers: 4)
Therapeutic Advances in Vaccines     Hybrid Journal   (Followers: 1)
Therapeutic Drug Monitoring     Hybrid Journal   (Followers: 5)
Therapeutic Innovation & Regulatory Science     Hybrid Journal   (Followers: 7)
Thérapie     Full-text available via subscription   (Followers: 1)
TheScientist     Free   (Followers: 6)
Toxicological & Environmental Chemistry     Hybrid Journal   (Followers: 2)
Toxicological Research     Hybrid Journal  
Toxicological Sciences     Hybrid Journal   (Followers: 11)
Toxicology     Hybrid Journal   (Followers: 19)
Toxicology and Applied Pharmacology     Hybrid Journal   (Followers: 25)
Toxicology and Industrial Health     Hybrid Journal   (Followers: 6)
Toxicology in Vitro     Hybrid Journal   (Followers: 12)
Toxicology International     Full-text available via subscription   (Followers: 5)
Toxicology Letters     Hybrid Journal   (Followers: 16)
Toxicology Mechanisms and Methods     Hybrid Journal   (Followers: 9)
Toxicology Research     Partially Free   (Followers: 8)
Toxicon     Hybrid Journal   (Followers: 5)
Toxicon : X     Open Access  
Toxin Reviews     Hybrid Journal  
Translational Psychiatry     Open Access   (Followers: 14)
Trends in Peptide and Protein Sciences     Open Access  
Trends in Pharmacological Sciences     Full-text available via subscription   (Followers: 21)
Tropical Journal of Pharmaceutical Research     Open Access  
Ukrainian Biopharmaceutical Journal     Open Access  
Vascular Pharmacology     Hybrid Journal   (Followers: 2)
World Mycotoxin Journal     Hybrid Journal   (Followers: 3)
Yakugaku Zasshi     Open Access   (Followers: 1)
Zeitschrift für Phytotherapie     Hybrid Journal   (Followers: 1)
Актуальні питання фармацевтичної та медичної науки та практики     Open Access  
Фармацевтичний часопис     Open Access  

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Research Results in Pharmacology
Number of Followers: 0  

  This is an Open Access Journal Open Access journal
ISSN (Online) 2658-381X
Published by Pensoft Homepage  [58 journals]
  • Validation of structural-based virtual screening protocols with the PDB
           Code 3G0B and prediction of the activity of Tinospora crispa compounds as
           inhibitors of dipeptidyl-peptidase-IV

    • Abstract: Research Results in Pharmacology 8(1): 95-102
      DOI : 10.3897/rrpharmacology.8.76237
      Authors : Andri Prasetiyo, Shirly Kumala, Esti Mumpuni, Raymond R. Tjandrawinata : Introduction: Brotowali (Tinospora crispa) has been traditionally used as an antidiabetic drug. DPP-IV inhibitor as an antidiabetic will increase insulin secretion. It indirectly escalates incretin hormones, such as Glucagon-Like peptide-1 (GLP-1) which depends on glucose. This study predicts potential compounds from the Brotowali plants, such as DPP-IV inhibitors, using the Molegro Virtual Docker (MVD). Materials and methods: Before the molecular docking simulation, internal validation and external validation are necessary. Internal validation was carried out by re-docking the native ligands in the DPP-IV enzyme crystal structure (PDB codes 3G0B, 3W2T, and 3BJM). The external validation was carried out by simultaneous docking of 59 active compounds and 1918 inactive compounds (decoys) from the A Directory of Useful Decoys (DUD) database with PDB code 3G0B on 16 combinations, four search algorithms, and four functions scoring. Results and discussion: The molecular docking simulation was carried out on 50 compounds from the Brotowali plant and alogliptin as standard compounds with PDB code 3G0B. The best results of the docking method validation yielded the RMSD values of 0.43 and EF1% of 20.34 and EF20% of 3.1 (the combination of search algorithm Moldock optimizer and scoring function Moldock score). The re-rank score of 5 compounds from the Brotowali plant (Rumphioside C, Borapetoside E, Borapetoside F, Rumphioside I, and 6’-O-Lactoyl Borapetoside B) were -107.7 kcal/mol; -105.4 kcal/mol; -104.2 kcal/mol, and -102.8 kcal/mol. Alogliptin (standard ligands) had a re-rank score of -101.6 kcal/mol. The combination of search algorithms MolDock optimizer and scoring function MolDock score is a valid protocol with a good result. The similarity of the binding sites of Borapetoside E and 6’-O-Lactoyl Borapetoside B is 75% when compared to the alogliptin binding sites (Glu 205, Glu 206, Tyr 547). Conclusion: Based on the re-rank score and binding sites similarity, Borapetoside E and 6’-O-Lactoyl Borapetoside B have potential as an antidiabetic drug with a mechanism of action of DPP-IV inhibitors. HTML XML PDF
      PubDate: Thu, 31 Mar 2022 18:06:06 +030
       
  • Evaluation of the pharmacological activity of hybrid organotin
           compounds in a B16 melanoma model in the classical and metronomic
           administration modes

    • Abstract: Research Results in Pharmacology 8(1): 85-93
      DOI : 10.3897/rrpharmacology.8.76363
      Authors : Margarita A. Dodokhova, Andrey V. Safronenko, Inga M. Kotieva, Margarita S. Alkhuseyn-Kulyaginova, Dmitry B. Shpakovsky, Elena R. Milaeva : Introduction: In modern medical chemistry, much attention is paid to the search for new antimetastatic agents based on metal compounds. Organotin compounds promise to be good candidates as the treatment of malignant neoplasms. In order to reduce a possible nonspecific toxic effect of tin compounds and to expand the intended therapeutic use, the paper presents hybrid tin (IV) complexes with Sn-S bond containing a fragment of 2,6-di-tert-butylphenol. The aim of the study was to evaluate the antitumor and antimetastatic effects of bis (3,5-di-tert-butyl-4-hydroxyphenylthiolate) dimethylolol (Me3) and (3,5-di-tert-butyl-4-hydroxyphenylthiolate) triphenylolol (Me5) in a model of transplanted melanoma tumor in B16 mice in classical and metronomic administration mode. Materials and methods: The efficacy of organotin compounds was studied in a model of a transplanted tumor with spontaneous metastasis of C57Bl/6 (female) melanoma B16 mice using the following indicators: average life expectancy, inhibition of tumor growth by weight, tumor mass, and metastasis inhibition index. Results and discussion: The most pronounced antimetastatic effect (54% and 36%) is achieved with a five-fold intraperitoneal injection of Me3 and Me5 at the total doses of 375 mg/kg and 250 mg/kg. The comparable results of the efficacy were obtained in the classical and metronomic modes of the injection of hybrid organotin compounds. With an increase in the injected dose, there is an effect of activating the tumor process with the generalized metastasis. Conclusion: Bis dimethylolol (Me3) and triphenylolol (Me5) compounds demonstrate both a pronounced antimetastatic activity and a multidirectional effect on the growth of the primary focus and the metastasis in lungs, depending on an injected dose. HTML XML PDF
      PubDate: Thu, 31 Mar 2022 18:05:51 +030
       
  • Experimental study of new derivatives of 3-hydroxypyridine as
           pharmacological agents for the correction of ischemic brain injury after
           intracerebral hemorrhage

    • Abstract: Research Results in Pharmacology 8(1): 71-83
      DOI : 10.3897/rrpharmacology.8.80378
      Authors : Olesya V. Shcheblykina, Dmitry V. Shcheblykin, Konstantin S. Trunov, Anton P. Danilenko, Vladimir S. Lipatov : Introduction: Limiting the action of secondary injury factors can improve the prognosis in acute cerebral accidents. The aim of the investigation is to study the neuroprotective effects of 3-hydroxypyridine derivatives. Materials and methods: The study was performed in Wistar rats. An intracerebral hemorrhage (ICH) model was used. The animals were once administered intraperitoneally with the test drugs 1 hour before the surgery and on the 1st, 2nd and 3rd days. The registration of behaviors and condition of the animals on days 1, 3, 7 and 14 and the morphological examination of the brain were performed. Results and discussion: The use of the substances LKhT 4-97 and LKhT 11-02 in the treatment of experimental ICH had a positive effect on the survival rate of the animals and on the resolution rate of pathological signs (p
      PubDate: Thu, 31 Mar 2022 18:05:36 +030
       
  • The effectiveness of Soderm® – forte gel and a new injectable dosage
           form of Rexod® in the complex treatment of experimental periodontitis in
           rats

    • Abstract: Research Results in Pharmacology 8(1): 51-58
      DOI : 10.3897/rrpharmacology.8.79641
      Authors : Pavel A. Galenko-Yaroshevsky, Kristina V. Tseluiko, Valeriy K. Leontev, Mark A. Zadorozhniy, Viktor L. Popkov, Anait V. Zelenskaya, Sergey A. Babichev, Andrey V. Zadorozhniy, Sonya V. Meladze : Introduction: Insufficient effectiveness of traditional drug therapy in a treatment of patients with chronic generalized periodontitis, as well as high social significance of this problem, determines the need to search for new drugs and their compositions aimed at solving it. Aim of the study: To increase the efficacy of complex treatment of periodontitis with the administration of Soderm®-Forte gel and a new injectable form of Rexod®. Materials and methods: Experiments were performed in 50 male Wistar rats. Experimental periodontitis (EP) was simulated by ligation of the necks of lower incisors. We studied the animals with intact periodontium, untreated EP, and when traditional drug therapy (TDT), as well as the combinations of TDT with Soderm®-Forte gel and additionally with the new injectable dosage form (NIF) of Rexod® were administered. The general condition, behavior, nutrition and body weight of the animals were evaluated. The Schiller-Pisarev test and the Muhlemann-Cowell bleeding index were used, and the amount of crevicular fluid (CF) was measured. The contamination of the marginal gum with microorganisms was determined. Results and discussion: The TDT in EP has a moderate therapeutic effect, which does not lead to a sufficiently high pharmacotherapeutic effect, whereas the combinations of TDT with Soderm®-Forte and, to a greater extent, TDT with Soderm®-Forte and NIF of Rexod® have high therapeutic efficacy, which is statistically confirmed by a sharp decrease in the amount of CF, the Schiller-Pisarev test and the Muhlemann-Cowell bleeding index, as well as absolute suppression of pathogenic microorganisms. Conclusion: The combinations of TDT with Soderm®-Forte gel and NIF of Rexod® in EP in rats can significantly increase the effectiveness of the treatment. The data obtained indicate the expediency of the administration of Soderm®-Forte gel, as well as its combination with NIF of Rexod® in dental practice in the complex therapy of patients with periodontitis. HTML XML PDF
      PubDate: Thu, 31 Mar 2022 18:05:23 +030
       
  • Nortriptyline overcomes corticosteroid resistance in NK and NKT-like
           cells from peripheral blood of patients with chronic obstructive pulmonary
           disease

    • Abstract: Research Results in Pharmacology 8(1): 59-70
      DOI : 10.3897/rrpharmacology.8.75467
      Authors : Aliaksei G. Kadushkin, Anatoli D. Tahanovich, Lyudmila V. Movchan, Volha V. Dziadzichkina, Olga V. Levandovskaya, Tatsiana V. Shman : Introduction: An antidepressant nortriptyline potentiates glucocorticoid (GC) action with synergistic suppression of inflammatory mediator release, but the precise molecular mechanism is unknown. Materials and methods: Peripheral blood cells from patients with chronic obstructive pulmonary disease (COPD) (n = 21) were incubated with nortriptyline (1 µM or 10 µM), budesonide (10 nM), or their combinations, followed by stimulation with phorbol myristate acetate (PMA) and ionomycin. Cytokine production, glucocorticoid receptor β (GRβ), histone deacetylase 2 (HDAC2) and histone H4 acetylation of K8 (HAT) expression, p65 NF-kB and p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation in NK (CD3-CD56+) and NKT-like (CD3+CD56+) cells were analyzed by flow cytometry. Results: We observed that nortriptyline (10 µM) significantly attenuated the effects of PMA/ionomycin on the synthesis of interferon γ (IFNγ), interleukin 4 (IL-4), and IL-8, expression of GRβ and HAT, as well as p65 NF-kB and p38 MAPK phosphorylation in NK and NKT-like cells, whereas nortriptyline (1 µM) only inhibited IL-4 production by NK and NKT-like cells. Discussion: The combination of nortriptyline (10 µM) and budesonide decreased IFNγ, tumor necrosis factor α, IL-4, IL-8, and GRβ expression, as well as phosphorylated p38 MAPK and p65 NF-κB levels by NK and NKT-like cells above that of budesonide alone. Furthermore, the same association of drugs enhanced HDAC2 expression in NK and NKT-like cells. Conclusion: Collectively, our results show that nortriptyline might enhance GC function through modulation of HAT, HDAC2, GRβ, phospho-p38 MAPK expression. These data provide a strong rationale for combining nortriptyline with budesonide to treat COPD. HTML XML PDF
      PubDate: Thu, 31 Mar 2022 18:05:09 +030
       
  • Cytotoxic activities of ethanolic crude extracts from fruiting bodies
           of bamboo mushrooms (Dictyophora spp.) against cholangiocarcinoma cells

    • Abstract: Research Results in Pharmacology 8(1): 33-41
      DOI : 10.3897/rrpharmacology.8.72098
      Authors : Pathanin Chantree, Sirilak Chumkiew, Mantana Jamklang, Pongsakorn Martviset : Introduction: Cholangiocarcinoma (CCA) is a highly progressive tumor. The standard chemotherapy varies in its effectiveness, with generally low efficacy. So, the discovery of novel chemotherapy is still required. The objective of this preliminary study was to determine the cytotoxic effects induced by three kinds of bamboo mushrooms (Dictyophora indusiata or Chinese bamboo mushroom; Ch-DTP, Short skirt bamboo mushroom (Thai isolate); Th-DTP, and orange skirt bamboo mushroom; Or-DTP) on CCA cells. Materials and methods: CCA cell lines, including CL-6, HuCCT1, HuH28, and OUMS normal fibroblast cells, were treated with various concentrations of DTP extracts. The MTT assay was used to determine cytotoxicity, and cell morphology was observed by using phase-contrast microscopy. Results and discussion: The results suggested that Ch-DTP effectively killed all three CCA cell lines in both low (0.3 mg/mL) and high (0.6 mg/mL) doses, but Th-DTP and Or-DTP had significantly reduced cell viability only at high doses (p
      PubDate: Wed, 16 Mar 2022 23:53:21 +020
       
  • Study of dose-dependent actoprotective effect of ATACL on physical
           

    • Abstract: Research Results in Pharmacology 8(1): 13-22
      DOI : 10.3897/rrpharmacology.8.75981
      Authors : Anastasia D. Gerashchenko, Dmitry I. Pozdnyakov, Andrey V. Voronkov : Introduction: The aim of the study was to investigate the dose-dependent actoprotective effect of ATACL on physical performance and psychoemotional status of animals under conditions of exhausting exercise. Materials and methods: Outbred male mice (23–25 g) were used in the experiment. The test compound in various dosages, as well as the reference drug, were administered intragastrically 60 minutes before the forced swimming test for 10 days of the experiment. At the end of the physical activity, the psychoemotional status of the animals was assessed in the Open Field (OF) and Elevated plus maze (EPM) tests. Results and discussion: In the course of the experiment, it was found that under conditions of exhausting physical execise, a smooth increase in performance was observed in the group that had received the test compound 4-hydroxy-3,5-di-tert butyl cinnamic acid (ATACL) at a dosage of 100 mg/kg for 10 days. The peak of performance was recorded on the 8th day, which was 47.3% (p
      PubDate: Wed, 16 Mar 2022 16:29:45 +020
       
  • Development of novel effective agents from 1H-indolylammonium
           trifluoroacetates effective against conditionally pathogenic
           microorganisms

    • Abstract: Research Results in Pharmacology 8(1): 43-50
      DOI : 10.3897/rrpharmacology.8.73329
      Authors : Irina S. Stepanenko, Semen A. Yamashkin, Tatyana N. Platkova, Anastasia I. Kiryutina, Ilya N. Sorokvasha : Introduction: The problem of antibiotic resistance of microorganisms is becoming more urgent in the twenty-first century. More and more pathogenic microbes are becoming resistant to two or more antibiotics. This problem has become worse into the COVID-19 pandemic. The search for new compounds with antimicrobial activity is one of the principles for overcoming the antibiotic resistance of microorganisms. Materials and methods: Methods for the preparation, isolation, and identification of salts of 2,3,5-trimethyl-, 1,2,3,5-tetramethyl-, 2,3-dimethyl-5-methoxy-, 5-methoxy-1,2,3-trimethyl-1H-indole-6-amines and trifluoroacetic acid were developed and laboratory microbiological studies of them for antimicrobial activity were carried out. Sensitivity of the test-strains of microorganisms to the new compounds was studied. A method of serial dilutions to determine the minimal inhibitory concentration (MIC) of the compounds under study was used in the study. Results and discussion: The compounds 5–8 showed a pronounced antibacterial activity against the test strains of microorganisms in vitro with MIC from 0.98 µg/mL to 125.0 µg/mL. The prospects for targeted synthesis of biologically active compounds which are derivatives of 1H-indolylamines with a trifluoromethyl group in the molecule were determined, and after additional studies, the compounds 5–8 may find application as water-soluble synthetic antimicrobial agents. Conclusion: The laboratory microbiological screening of showed that they have an antimicrobial effect that exceeds the activity of the reference drug, dioxidine. The presence of molecular mechanisms predicted in silico in the spectrum of biological activity of the studied compounds, such as Pseudolysin inhibitor, Omptin inhibitor, Undecaprenyldiphospho-muramoylpentapeptide beta-N-acetylglucosaminyltransferase inhibitor, UDP-epimerase inhibitor, Bacterial efflux pump inhibitor, suggests the presence of antimicrobial activity against gram-positive and gram-negative microorganisms. Trifluoroacetates 2,3,5-trimethyl-1H-indole-6-ammonium (5), 1,2,3,5-tetramethyl-1H-indole-6-ammonium (6), 2,3-dimethyl-5-methoxy-1H-indole-6-ammonium (7), 1,2,3-trimethyl-5-methoxy-1H-indole-6-ammonium (8), after additional studies, may find application as water-soluble synthetic antimicrobial agents. HTML XML PDF
      PubDate: Wed, 16 Mar 2022 11:45:06 +020
       
  • Study of pharmacokinetic of new peptide drug
           1-deamino-arginine-vasotocin for hypernatremia correction

    • Abstract: Research Results in Pharmacology 8(1): 23-31
      DOI : 10.3897/rrpharmacology.8.71802
      Authors : Vera M. Kosman, Natalya M. Faustova, Marina V. Karlina, Valery G. Makarov, Marina N. Makarova : Introduction: The pharmacokinetics studies are some of the necessary parts of the drugs preclinical investigations. Pharmacokinetic properties of new peptide drug 1-deamino-arginine-vasotocin (dAVT) in the form of an injection solution for intravenous and intramuscular administration for hypernatremia correction were investigated. Materials and methods: The study was carried out on male rats and rabbits with a single intravenous administration of the drug in three doses, a single intramuscular administration in one dose and multiple administration to rats in one dose. To determine natriiuretic peptide concentration in blood plasma, tissues, and excretes, assays based on a sodium level change measurement using a biochemical analyzer have been developed and validated. Pharmacokinetic parameters were calculated by the model-independent method of statistical moments. Results and discussion: The pharmacokinetics of the drug was found to be linear after a single administration of dAVT drug in the dose range 3–10 μg/kg for rats and rabbits. The relative bioavailability of dAVT after intramuscular and intravenous administrations was more than 30%. After a biomarker content change, the active substance was intensively distributed into highly vascularized organs (spleen), the organs that provide metabolism and subsequent excretion (liver and kidneys), whereas it hardly reached moderately and weakly vascularized tissues (muscles, omentum). Less than 10% dAVT was excreted with urine; no dAVT was determined in feces; and repeated administration did not lead to its cumulation. Conclusion: Pharmacokinetics parameters of new nonapeptide drug 1-deamino-arginine-vasotocin were evaluated after original analytical biomarker approach. The study included all main areas necessary to characterize the original drug pharmacokinetic. HTML XML PDF
      PubDate: Wed, 16 Mar 2022 11:09:04 +020
       
  • Synthesis, molecular docking, ADMET study and in vitro pharmacological
           research of
           7-(2-chlorophenyl)-4-(4-methylthiazol-5-yl)-4,6,7,8-tetrahydroquinoline-2,5(1H,3H)-dione
           as a promising non-opioid analgesic drug

    • Abstract: Research Results in Pharmacology 8(1): 1-11
      DOI : 10.3897/rrpharmacology.8.80504
      Authors : Aleksey D. Kravchenko, Natalia V. Pyatigorskaya, Galina E. Brkich, Larysa V. Yevsieieva, Alexander V. Kyrychenko, Sergiy M. Kovalenko : Introduction: The discovery of novel drugs that can block the transmission of pain signals for treating the pain of various etiologies is an urgent topic in pharmaceutics. The aim of this paper is to synthesize and to investigate in vitro and in silico characteristics of a promising novel compound: 7-(2-chlorophenyl)-4-(4-methylthiazol-5-yl)-4,6,7,8-tetrahydroquinoline-2,5(1H,3H)-dione (HSV-DKH-0450). Materials and methods: The specific activity and the inhibitory mechanism of HSV-DKH-0450 were studied using the HEK293 culture cells expressing the IPTG-induced TRPA1 ion channels. Cardiotoxicity was determined by estimating the binding of HSV-DKH-0450 to the hERG channel. Inhibition of human liver cytochromes was determined by the effect on the activity of cytochromes 1A2, 2C9, 2D6, 2C8, and 3A4. Cellular toxicity was assessed by the effect on the viability of human hepatocytes. ADMET properties were evaluated using admetSAR and SwissADME web-based tools. Molecular docking was carried out using AutoDock Vina tools to predict the binding affinity of all HSV-DKH-0450 stereoisomers toward the TRPA1 and TRPV1 receptors. Results and discussion: In silico predictions of ADMET properties of HSV-DKH-0450 showed that it has optimal pharmaceutical profiles. A series of in vitro pharmacological studies revealed that HSV-DKH-0450 is a promising antagonist of the TRPA1 ion channel with the IC50 of 91.3 nM. The molecular docking of HSV-DKH-0450 stereoisomers against the TRPA1 and TRPV1 receptors demonstrates that they all are characterized by an approximately similar high binding affinity. Conclusion: The obtained data for substance HSV-DKH-0450 look promising for its further development as a potential therapeutic agent for pain relief. Graphical abstract: HTML XML PDF
      PubDate: Wed, 16 Feb 2022 11:36:20 +020
       
  • Design and evaluation of pharmacological properties of a new
           1,3,4-thiadiazolylamide derivative of 2-propylpentanoic acid

    • Abstract: Research Results in Pharmacology 7(4): 89-98
      DOI : 10.3897/rrpharmacology.7.70179
      Authors : Alexandr S. Malygin, Victor V. Yasnetsov : Introduction: The use of the pharmacophoric approach is a promising direction for modifying the chemical structure of 2-propylpentanoic (valproic) acid in order to obtain new drugs. Materials and methods: In the experiments on mice, acute toxicity, neurotoxicity, antiepileptic activity and analgesic effect of N-(5-ethyl-1,3,4-thiadiazol-2-yl)-2-propylpentanamide (valprazolamide) were evaluated. LD50 was determined by probit analysis. Neurotoxicity was determined in a rotarod test and a bar test in mice. The effects of valprazolamide on the exploratory behavior of mice in open field test and in a light/dark transition test were evaluated. Its antiepileptic activity was tested in mice against seizures induced by maximal electroshock, pentylenetetrazole (scPTZ); isoniazid, thiosemicarbazide, pilocarpine, and camphor. The analgesic effect was studied in a hot plate test. Results and discussion: N-(5-ethyl-1,3,4-thiadiazol-2-yl)-2-propylpentanamide was obtained by introducing pharmacophores into the structure of 2-propylpentanoic acid: a substituted amide group and an electron-donor domain of 1,3,4-thiadiazole. The LD50 value for intraperitoneal administration of a new 2-propylpentanoic acid: derivative to mice was 924.8 mg/kg, and the TD50 value in the rotarod test and the bar test were 456.7 mg/kg and 546.7 mg/kg, respectively. The suppression of orienting responses in the animals was noted when it was administered in neurotoxic doses. Valprazolamide showed the most antiepileptic activity on models of MES, scPTZ and isoniazid antagonism tests. The ED50 values were 138.4 mg/kg, 74.5 mg/kg, and 126.8 mg/kg, respectively. The therapeutic indices for these models of epilepsy were 6.7; 12.4; 7.3, and protective index – 3.3; 6.1 and 3.6, respectively. In the hot plate test, valprazolamide increased the latency period before a defensive response to a thermal stimulus (ED50 165 mg/kg). Conclusion: N-(5-ethyl-1,3,4-thiadiazol-2-yl)-2-propylpentanamide is a new 1,3,4-thiadiazolylamide derivative of 2-propylpentanoic acid with antiepileptic and analgesic activities, which belongs to the group of low-toxic agents. Graphic abstract N-(5-ethyl-1,3,4-thiadiazol-2-yl)-2-propylpentanamide (3D) LD50=924.8 mg/kg (mice, intraperitoneally) TD50=456.7 mg/kg (rotarod, mice, intraperitoneally) ED50=138.4 mg/kg (MES, mice, intraperitoneally) ED50=74.5 mg/kg (scPTZ, mice, intraperitoneally) HTML XML PDF
      PubDate: Mon, 20 Dec 2021 21:39:01 +020
       
  • Impact of organotin compounds on the growth of epidermoid Lewis
           carcinoma

    • Abstract: Research Results in Pharmacology 7(4): 81-88
      DOI : 10.3897/rrpharmacology.7.71455
      Authors : Margarita A. Dodokhova, Andrei V. Safronenko, Inga M. Kotieva, Margarita S. Alkhuseyn-Kulyaginova, Dmitry B. Shpakovsky, Elena R. Milaeva : Introduction: Search for new compounds with a broad antitumor and antimetastatic potency due to multiple targeting remains important in medicinal chemistry, pharmacology and oncology. We report the efficacy of hybrid organotin agents bis-(3,5-di-tert-butyl-4-hydroxyphenylthiolate) dimethyltin (Ме3) and (3,5-di-tert-butyl-4-hydroxyphenylthiolate) triphenyltin (Ме5). Materials and methods: The compounds were administered to mice bearing the spontaneously metastatic epidermoid Lewis lung carcinoma (LLC). The efficacy of the treatment was evaluated by mean life span, percentage of tumor growth inhibition, number of lung metastases, frequency of metastasis, tumor weight 21 days after tumor cell inoculation, and a degree of lung damage according to the method of D. Tarin and J.E. Price. Results and discussion: For new organotin compounds containing an antioxidant protective fragment of 2,6-di-tert-butylphenol, moderate antitumor and pronounced antimetastatic effects were revealed in the Lewis model of epidermoid lung carcinoma; more active for Me5. Some features of the development of the process of metastasis were recorded with the introduction of various doses of hybrid organotin compounds. Conclusion: Substances Ме3 and Ме5 possess specific activity on the model under investigation, which allows one to suggest these organotins as promising series of antitumor and antimetastatic agents with multiple targeting mode of action. HTML XML PDF
      PubDate: Mon, 20 Dec 2021 12:09:25 +020
       
  • Optimization of premedication of patients with arterial hypertension and
           severe ventricular rhythm disturbances with Amiodarone-associated
           thyrotoxicosis

    • Abstract: Research Results in Pharmacology 7(4): 55-62
      DOI : 10.3897/rrpharmacology.7.78137
      Authors : Andrey V. Safronenko, Sergey V. Lepyavka, Igor A. Demidov, Marina I. Nazheva, Yuri S. Maklyakov : Introduction: The effectiveness of premedication of patients with arterial hypertension and severe ventricular rhythm disturbances against the background of Amiodarone-associated thyrotoxicosis, high anxiety and cyclothymiae disorders should be based on the pharmacological positions of the need to reduce the risk of dangerous adverse cardiovascular reactions. Materials and methods: During the research, a clinical group of 114 patients with arterial hypertension, severe ventricular arrhythmias and Amiodarone-associated type I thyrotoxicosis was formed: four subgroups were identified. In Subgroup 1 (n=22), no premedication was given. In Subgroup 2 (n=32), premedication was given with Diazepam and magnesium sulfate in a prolonged mode. In Subgroup 3 (n=30), the patients received Diazepam the day before surgery. In Subgroup 4 (n=30), premedication was given with Midazolam. A dynamic assessment of the severity of anxiety, depression, sedation and daily monitoring of blood pressure and ECG were carried out. Results and discussion: After surgery, in Subgroup 1, the level of anxiety and depression increased. In all other Subgroups, regardless of the type of premedication, the use of benzodiazepines was accompanied by a decrease in the level of anxiety after surgery. A decrease in pressure load and an increase in the stability of the parameters of systemic hemodynamics were registered in Subgroup 2 of patients, whereas in Subgroup 4 of patients, the pressure load increased while limiting the differences in blood pressure values during the day. After surgery, in Subgroup 2, cardiac rhythm disturbances were less common; in Subgroup 3, the structure of rhythmogenesis disturbances in the heart almost did not change, and in Subgroup 4, there was an unfavorable trend of an increase in the frequency of supraventricular, single and group ventricular extrasystoles. Conclusion: The prolonged premedication with long-acting benzodiazepines and magnesium preparations in patients with arterial hypertension, ventricular rhythm disturbances against the background of Amiodarone-associated thyrotoxicosis reduces the level of anxiety, as well as the risk of developing cardiovascular complications and instability of systemic hemodynamics. HTML XML PDF
      PubDate: Thu, 16 Dec 2021 23:01:46 +020
       
  • Study of analgesic activity and effects of new dipharmacophores –
           nebracetam and cyclooxygenase-2 inhibitors derivatives on the cognitive
           abilities of rats

    • Abstract: Research Results in Pharmacology 7(4): 71-79
      DOI : 10.3897/rrpharmacology.7.78463
      Authors : Vitaliy S. Slyusarenko, Ivan S. Koklin, Sergiy M. Kovalenko, Vladimir P. Chuev, Alexey A. Shabalin, Vladimir V. Gureev, Mikhail V. Korokin : Introduction: The aim of the present study was to research the analgesic activity and effect of new dipharmacophore compounds consisting of substances with proven therapeutic activity, namely nebracetam–ibuprofen (NRIP), nebracetam–dexibuprofen (NRDIP), nebracetam–niflumic acid (NRNFA), and nebracetam–mefenamic acid (NRMFA), on the cognitive abilities of rats. Materials and methods: The experimental study was performed in 110 Wistar rats (male/female ratio 50/50%), weighing 180–200 g, and 50 laboratory mice (male/female ratio 50/50%) weighing 18–22 g. The study of the analgesic activity was carried out using the acetic acid writhing test and the hot plate test. The effect on the cognitive abilities of rats was studied using the pattern recognition test in a model of neurotrauma caused by a drop-weight. Results and discussion: It has been shown that the administration of dipharmacophores nebracetam–ibuprofen (NRIP), nebracetam–dexibuprofen (NRDIP), nebracetam–niflumic acid (NRNFA) as well as nebracetam–mefenamic acid (NRMFA) in the tested dosages leads to a statistically significant (p
      PubDate: Thu, 16 Dec 2021 14:51:46 +020
       
  • “The obesity paradox” in patients with atrial fibrillation according
           to the results of the REKUR-AF study

    • Abstract: Research Results in Pharmacology 7(4): 63-69
      DOI : 10.3897/rrpharmacology.7.78134
      Authors : Inna L. Polshakova, Sergey V. Povetkin, Alexey Y. Gaponov : Introduction: to evaluate the effect of excess body weight (EBW) and obesity on the survival of patients with atrial fibrillation (AF) in the REKUR-AF study. Materials and methods: A subanalysis of patients with AF included in the REKUR-AF (382 people) study was performed. Survival rates were analyzed in three patient groups: patients with normal body mass index (BMI), EBW and obesity. Then the nature and significance of the influence of the studied factor on the prognosis in patients with AF were assessed. Results and discussion: Patients with AF and normal BMI were significantly older than those with obesity and EBW (p
      PubDate: Thu, 16 Dec 2021 10:38:59 +020
       
  • Modern approaches to pharmacotherapy of tuberculosis infection in children

    • Abstract: Research Results in Pharmacology 7(4): 47-53
      DOI : 10.3897/rrpharmacology.7.66627
      Authors : Vasiliy E. Novikov, Natalia E. Usacheva, Tatyana V. Myakisheva : Anti-TB drugs for children: Aetiotropic therapy is used for the treatment of tuberculosis (TB) in children, as well as in adult patients. Anti-tuberculosis drugs (anti-TB drugs) are divided into 3 lines, taking into account drug sensitivity in Mycobacterium tuberculosis (MBT). First-line anti-TB drugs (basic) are used to treat TB caused by drug-susceptible MBT. Second- and third-line (reserve) drugs are recommended for the treatment of MBT-induced multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB, respectively. Stages and regimens to treat tuberculosis: Chemotherapy of tuberculosis in children is carried out in 2 stages (intensive treatment and continuation of treatment) and includes 5 regimens. Each regimen assumes a certain combination of anti-TB drugs, indicating the duration and frequency of their administration. The final chemotherapy regimen is chosen only according to the results of determining the drug sensitivity. To improve the TB epidemic among children, it is important to improve the regimens for the use of anti-TB drugs. The effectiveness of anti-tuberculosis pharmacotherapy is largely determined by the MBT sensitivity and the rational choice of the chemotherapy regimen. The wrong choice of a chemotherapy regimen or its violation threatens to reduce the effectiveness of pharmacotherapy and expand the spectrum of resistance of the pathogen. The development of fixed-dose combination anti-TB drugs and special dosage forms for children will improve the quality of chemotherapy and adherence to treatment. Pharmacoeconomic studies are needed to increase the effectiveness of drug pharmacotherapy for tuberculosis infection in children and to optimize the costs of its implementation. HTML XML PDF
      PubDate: Fri, 3 Dec 2021 11:08:09 +0200
       
  • Is antibiotics overuse justified when immediate intervention is not
           possible' A rapid evidence review

    • Abstract: Research Results in Pharmacology 7(4): 41-46
      DOI : 10.3897/rrpharmacology.7.77709
      Authors : Nour Ibrahim, Ziad Noujeim, Georges Aoun, Abbass El-Outa : Introduction: This review revisits clinical use of antibiotics for most common acute oro-dental conditions; we aim to provide evidence governing antibiotics use when access to oral healthcare is not available, as during the ongoing outbreak of the severe acute respiratory syndrome coronavirus 2. Materials and methods: In this rapid review, articles were retrieved after conducting a search on PubMed and Google Scholar. Relevant publications were selected and analyzed. Most recent systematic reviews with/without meta-analyses and societal guidelines were selected. Data were extracted, grouped, and synthesized according to the respective subtopic analysis. Results and discussion: There was evidence supporting the use of antibiotics in common oro-dental conditions as temporary measure when immediate care is not accessible, such as in case of localized oral swellings as well as to prevent post-extraction complications. No sufficient evidence could be found in support of antibiotic use for pain resulting from pulpal origin. Conclusion: Antibiotic use may be justified to defer treatment temporarily or reduce risk of complications in case of localized infection and tooth extraction, when no access to immediate dental care is possible. Graphical abstract: HTML XML PDF
      PubDate: Fri, 3 Dec 2021 11:08:02 +0200
       
  • Pharmacological properties of selenium and its preparations: from
           antioxidant to neuroprotector

    • Abstract: Research Results in Pharmacology 7(4): 29-40
      DOI : 10.3897/rrpharmacology.7.73051
      Authors : Igor F. Belenichev, Nadia O. Gorchakov, Iryna B. Samura, Natalia V. Savchenko, Nina V. Bukhtiyarova, Olena O. Popazova : Selenium is an essential component of more than two dozen enzymes and other selenoproteins that play critical roles in reproduction, DNA synthesis, thyroid hormone metabolism, and protection from oxidative damage and infection. Selenium has a protective action against some forms of cancer and cardiovascular diseases, modulates levels of inflammatory mediators, promotes to maintain bone homeostasis and protects against bone loss. Selenium significance as a cardioprotective agent may be associated not only with its antioxidant properties, but also with its ability to prevent inflammation, autophagy, as well as the intrinsic and extrinsic apoptosis pathways. Signaling pathways, such as p-AMPK, PARP, Nrf2, STAT, are involved in the protective effects of selenium. Selenium protects against cardiovascular damage by increasing the survival rate of cardiomyocytes, including a mitochondria-dependent pathway and autophagy through peroxisome proliferator-activated receptors. Research demonstrating neuroprotective and cardioprotective effects of selenium preparations – selenoline, selenocysteine and selenomethionine – is growing at a rapid rate. It has been established that these compounds are able to normalize the levels of heat shock proteins (HSP70), which limit the cytotoxic effects of free radicals, produce energotropic action, prevent a decrease in the membrane mitochondria charge, and the opening of the mitochondrial pore. Also regulate the expression of transmembrane factors NF-kB, c-fos, which is associated with their main biological function of chaperone proteins, providing protection of neurons from damage. In this review, we want to emphasize pharmacological role of Selenium and its derivatives on human health is very complex and has yet to be fully understood. HTML XML PDF
      PubDate: Fri, 3 Dec 2021 11:07:53 +0200
       
  • Genetically modified animals for use in biopharmacology: from research to
           production

    • Abstract: Research Results in Pharmacology 7(4): 11-27
      DOI : 10.3897/rrpharmacology.7.76685
      Authors : Alexey V. Deykin, Olesya V. Shcheblykina, Elena E. Povetka, Polina A. Golubinskaya, Vladimir M. Pokrovsky, Liliya V. Korokina, Olesya A. Vanchenko, Elena V. Kuzubova, Konstantin S. Trunov, Viktor V. Vasyutkin, Alexandra I. Radchenko, Anton P. Danilenko, Julia V. Stepenko, Indira S. Kochkarova, Veronika S. Belyaeva, Vladimir I. Yakushev : Introduction: In this review, the analysis of technologies for obtaining biologically active proteins from various sources is carried out, and the comparative analysis of technologies for creating producers of biologically active proteins is presented. Special attention is paid to genetically modified animals as bioreactors for the pharmaceutical industry of a new type. The necessity of improving the technology of development transgenic rabbit producers and creating a platform solution for the production of biological products is substantiated. The advantages of using TrB for the production of recombinant proteins: The main advantages of using TrB are the low cost of obtaining valuable complex therapeutic human proteins in readily accessible fluids, their greater safety relative to proteins isolated directly from human blood, and the greater safety of the activity of the native protein. The advantages of the mammary gland as a system for the expression of recombinant proteins: The mammary gland is the organ of choice for the expression of valuable recombinant proteins because milk is easy to collect in large volumes. Methods for obtaining transgenic animals: The modern understanding of the regulation of gene expression and the discovery of new tools for gene editing can increase the efficiency of creating bioreactors for animals and help to obtain high concentrations of the target protein. The advantages of using rabbits as bioreactors producing recombinant proteins in milk: The rabbit is a relatively small animal with a short duration of gestation, puberty and optimal size, capable of producing up to 5 liters of milk per year per female, receiving up to 300 grams of the target protein. HTML XML PDF
      PubDate: Fri, 29 Oct 2021 08:30:56 +030
       
  • A new EPOR/CD131 heteroreceptor agonist EP-11-1: a neuroprotective effect
           in experimental traumatic brain injury

    • Abstract: Research Results in Pharmacology 7(4): 1-9
      DOI : 10.3897/rrpharmacology.7.75301
      Authors : Oleg V. Antsiferov, Roman F. Cherevatenko, Mikhail V. Korokin, Vladimir V. Gureev, Anastasia V. Gureeva, Mariya A. Zatolokina, Elena V. Avdeyeva, Lyudmila A. Zhilinkova, Inga M. Kolesnik : Introduction: EP-11-1 (UEHLERALNSS) is a short-chain erythropoietin derivative without have erythropoietic activity. It was created by modifying a peptide mimicking the spatial structure of the erythropoietin a-helix B pHBSP. One of the promising directions of its administration is the correction of morphofunctional disorders that occur in traumatic brain injury (TBI). Materials and methods: The study was performed in 160 male Wistar rats, weighing 180–200 g.TBI was simulated using the drop-weight method. To assess the emerging morphofunctional disorders and a degree of their correction, we used the severity of neurological deficit, indicators of locomotor activity and exploration, a marker of brain injury S100B and morphological examination. Results and discussion: The combined administration of a new EPOR/CD131 heteroreceptor agonist EP-11-1 with citicoline and trimetazidine led to a more pronounced correction of the neurological deficit when compared not only to the group of the ”untreated” animals, but also to the groups of animals to which these drugs had been administered as monotherapy (p < 0.05). The same tendency was also observed in the study of locomotor activity and exploration. A biochemical study showed that the administration of all three combinations led to a statistically significant (p < 0.05) decrease in the S-100B concentration compared not only to the group of “untreated” animals, but also to the groups of animals to which these drugs had been administered as a monotherapy. Conclusion: The results of the conducted experiments prove the most pronounced positive dynamics in the combined administration of the new EPOR/CD131 heteroreceptor agonist EP-11-1with citicoline and trimetazidine. HTML XML PDF
      PubDate: Sat, 9 Oct 2021 17:15:43 +0300
       
  • Studying the influence of Solcoseryl drug and vitamin C on the
           inflammatory reaction and proliferation of fibroblastic cells in the filed
           of polypropylene endoprosthesis implantation

    • Abstract: Research Results in Pharmacology 7(3): 83-91
      DOI : 10.3897/rrpharmacology.7.70931
      Authors : Viktor A. Lazarenko, Sergey V. Ivanov, Tatyana A. Pankrusheva, Ilya S. Ivanov, Evgeny G. Ob’edkov, Galina N. Goryainova, Lyubov A. Kopteva, Marina S. Chekmareva, Inna A. Ivanova, Natalya Ju. Ob’edkova : Introduction: Applying a coating on hernia endoprosthesis prevents recurrent anterior abdominal wall hernias, reduces inflammatory response and stimulates reparative processes in the area of its implantation. The aim of investigation was to study the effect of Solcoseryl and Vitamin C in a collagen-stimulating coating of hernioendoprosthesis on a morphological picture in anterior abdominal wall plastic surgery. Materials and methods: The study was performed on 180 laboratory mice divided into three groups of 60 animals each: the first group animals were implanted with polypropylene endoprostheses without a collagen-stimulating coating, the second group animals – polypropylene endoprostheses with a collagen-stimulating coating with Vitamin C, and the third group animals – polypropylene endoprostheses with a collagen-stimulating coating with Solcoseryl. The laboratory animals were withdrawn from the experiment on the 10th, 30th, 60th, and 90th days. The excised sections of the abdominal wall were stained with G+E to determine the nature of inflammation and the number of cell elements. Results and discussion: When using endoprostheses with a collagen-stimulating coating, the stages of inflammatory process proceeded more quickly, which was confirmed by a reliable (р ≤ 0.05) decrease in the number of neutrophils, macrophages and lymphocytes at all stages of the study. By the 90th day of the experiment, the number of fibroblasts in the control group was by 22.64% less than in the study groups with a coating. Conclusion: A cytological and histological analysis in the control group determined a consistent decrease in an exudative phase of inflammatory reaction. When using endoprosthesis with coatings, its acceleration and lower intensity was noted throughout the study. In the group with Solcoseryl, the formation of a dense connective capsule around the endoprosthesis indicates its quality and better adaptation of the endoprosthesis in body tissues. HTML XML PDF
      PubDate: Wed, 29 Sep 2021 16:50:04 +030
       
  • Pathogenetic features of acute naphazoline poisoning in children

    • Abstract: Research Results in Pharmacology 7(3): 93-100
      DOI : 10.3897/rrpharmacology.7.70242
      Authors : Ekaterina S. Karpushkina, Olga A. Zhdanova, Galina A. Batishcheva, Yulia A. Petukhova : Introduction: Acute poisoning by nasal decongestants is an important issue in pediatrics due to physiological and anatomical characteristics of the child’s body and pharmacokinetics of drugs in early childhood. Epidemiology: The number of poisonings by this group of drugs ranged from 4% to 39% during the period from 2000 to 2018. All the studies reported that the most severe degree of intoxication was observed in children aged 1–3 years. Mechanism of action of nasal decongestants: The peculiarity of selective alpha2-adrenergic agonists is that when taken orally, misused or overdosed, they lose their selectivity for the target receptor. As a result, the drug causes acute poisoning and most often this effect occurs in children and adolescents. Clinical features and diagnostic criteria: Clinical signs of acute poisoning can appear both as a result of an overdose of the nasal decongestants and due to a therapeutic use of the drug according to the instruction. The symptoms are manifested by hypothermia, skin pallor, bradycardia, arterial hypotension, profuse sweating, and acrocyanosis. Imidazoline receptors and new opportunities: It is assumed that toxic effect of topical decongestants occurs not only by activation of alpha2-adrenergic receptors, but also through their influence on the selective imidazoline receptors. Based on the structure of these drugs, it is assumed that imidazoline receptors are the primary binding site for these drugs. Conclusion: Understanding the described mechanisms of alpha2-adrenergic agonist action and peculiarities of the child’s symptoms in acute poisoning is necessary for the timely diagnosis and selection of the correct treatment strategy. HTML XML PDF
      PubDate: Wed, 29 Sep 2021 10:19:12 +030
       
  • Role of indole derivative SS-68 in increasing the frequency range of
           cardiac rhythm control (reflex stimulation of the sinoatrial node)

    • Abstract: Research Results in Pharmacology 7(3): 73-81
      DOI : 10.3897/rrpharmacology.7.75337
      Authors : Pavel A. Galenko-Yaroshevsky, Anatoly A. Nechepurenko, Tatiana G. Pokrovskaya, Nikolai L. Shimonovsky, Alexander S. Dukhanin, Konstantin F. Suzdalev, Polina D. Maslova, Natalia M. Makhnova, Vadim V. Shneivais, Valery G. Abushkevich, Anait V. Zelenskaya, Valeria V. Seletskaya, Saida K. Ahedzhak-Naguse, Konstantin G. Korotkov : Introduction: Cardiac pacing is indicated for sick sinus syndrome. It is performed with a pacemaker via electrodes implanted in the heart. This technique has several disadvantages. The search for alternative methods of cardiac pacing is underway. One of them is control of heart rhythm through stimulation of the tragus. Objective: To perform the reflex stimulation of the sinoatrial node and to study the influence of the SS-68 substance on it. Materials and methods: Two electrodes were fixed in the reflexogenic zone of rabbits’ auricles, volleys of electrical impulses from an electrical stimulator were applied to the electrodes, and the synchronization range of volley frequency and cardiac contractions was recorded. This range was re-recorded again after injecting the SS-68 substance (2-phenyl-1-(3-pyrrolidine-1-cyclopropyl)-1H-indole hydrochloride) intravenously at a dose of 50 µg/kg. In other experiments on frogs in a high-frequency electromagnetic field, the process of excitation of the area of the medulla oblongata associated with the heart rhythm was visualized. After the application of SS-68 (50 μM) to the surface of this zone, the process of its excitation was recorded. Results and discussion: Stimulation of the auricular reflexogenic zone of rabbits produced a synchronization of volley frequency and heart rate in the range from 173.5 ± 2.0 to 214.0 ± 1.8 per minute. SS-68 extended this range from 168.2 ± 1.9 to 219.4 ± 1.5 per minute. In the frog’s medulla oblongata, an area synchronous to the heart rhythm glowed in the high-frequency electromagnetic field. SS-68 increased the area of glow by 131.0%. Conclusion: The substance SS-68 increases the frequency range of heart rhythm control by activating reflex stimulation of the sinoatrial node. The main point of application of SS-68 is the medulla oblongata. Glow in the high-frequency electromagnetic field reflects the process of neuron excitation. The increase in the glow zone under the influence of SS-68 indicates synchronously excited neurons, which leads to the assimilation of the central heart rhythm generation by the sinoatrial node. HTML XML PDF
      PubDate: Fri, 24 Sep 2021 11:21:21 +030
       
  • Neuropharmacological characteristics of antidepressant action of a new
           3-substituted thietane-1,1-dioxide derivative

    • Abstract: Research Results in Pharmacology 7(3): 63-71
      DOI : 10.3897/rrpharmacology.7.68560
      Authors : Irina L. Nikitina, Gulnara G. Gaisina : Introduction: Due to severe burden of depressive disorders and a low rate of remission in patients receiving antidepressant therapy, there is an urgent need for developing novel agents with antidepressant action and a fundamentally new mechanism of action. 3-ethoxythietane-1,1-dioxide (N-199/1) is a new molecule that showed significant antidepressant properties when administered intraperitoneally once or repeatedly. The aim of the present study was to investigate the mechanism of action of N-199/1, using reserpine test. Materials and methods: N-199/1 (2 mg/kg and 4.86 mg/kg) and the reference drugs (imipramine and fluoxetine) were administered once intraperitoneally to outbred male mice 4 h (Experiment 1) and 18 h (Experiment 2) after a single intraperitoneal injection of reserpine (2.5 mg/kg). The severity of reserpine-induced symptoms (hypothermia, ptosis and akinesia) was assessed. Results and discussion: N-199/1 potentiated reserpine-induced hypothermia at both doses and reduced ptosis at a dose of 2 mg/kg when administered 4 h after reserpine. N-199/1 increased the duration of reserpine akinesia at a dose of 2 mg/kg when administered 18 h after reserpine and at a dose of 4.86 mg/kg when administered 4 h after reserpine. The effect of N-199/1 resembled the effect of fluoxetine and was dose-dependent. Conclusion: Based on the results obtained, it can be assumed that the antidepressant action of N-199/1 is due to its serotonin-positive properties, and probably the blockade of serotonin 5HT2A/2C receptors and/or α2-adrenergic receptors. The effect of N-199/1 is dose-dependent and resembles the effect of fluoxetine. Graphical abstract: HTML XML PDF
      PubDate: Tue, 21 Sep 2021 12:03:37 +030
       
  • Neuroprotective and cerebrovascular effects of endogenous
           N-Arachidonoyl-GABA and its putative Cox-2 metabolite – GABA conjugate
           with Prostaglandin E2

    • Abstract: Research Results in Pharmacology 7(3): 49-61
      DOI : 10.3897/rrpharmacology.7.70974
      Authors : Narine R. Mirzoyan, Nelly G. Khostikyan, Vahe S. Meliksetyan, Arpine A. Hakobyan, Tamara S. Gan’shina, Melanya G. Baghdasaryan, Anna M. Arakelyan, Anna V. Gnezdilova, Elena V. Kurza, Natalia M. Gretskaya, Vladimir V. Bezuglov, Lusine Danielyan, Ruben S. Mirzoyan : Introduction: The aim of the study was to compare the neuroprotective and cerebrovascular effects of bioactive, endogenous lipid – N-arachidonoyl-GABA (AA-GABA) and GABA conjugate with prostaglandin E2 (PGE2-GABA) by evaluation of a morphological state of rat brain tissue and lipofuscin levels under the condition of permanent focal brain ischemia, as well as cerebral circulation under the condition of global transient ischemia. Materials and methods: The study has been implemented using the models of the left middle cerebral artery occlusion (MCAO) and global transient ischemia of the brain. A morphological examination of the brain tissue, a registration of local blood flow by laser flowmeter, and quantitative measurement of lipofuscin by fluorescence spectroscopy were used. Results and discussion: AA-GABA and the putative COX-2 metabolite PGE2-GABA showed significant neuroprotective and cerebrovascular effects in rat models of global and focal cerebral ischemia. In the MCAO model, AA-GABA and PGE2-GABA at a dose of 2 mg/kg/day administered i.p. for 6 or 12 days led to: 1) significant restoration of neurons and glial cells with intracellular regeneration of cytoplasmic and nuclear structures, 2) decrease in brain tissue edema; 3) attenuated thrombosis and stasis, and 4) absence of large necrotic foci in rat brain tissue. AA-GABA and PGE2-GABA at the same dose prevented excessive accumulation of lipofuscin in both brain hemispheres in rats with MCAO. All the studied compounds increase cerebral blood circulation in rats subjected to global transient ischemia. However, the cerebrovascular effect of PGE2-GABA was superior to the activity of AA-GABA and all other tested compounds. AA-GABA and PGE2-GABA, unlike PGE2 and nimodipine, increase the cerebral blood flow in rats with global transient brain ischemia and have no influence on the intact animals. Apparently, the GABAergic vascular system of the brain is involved in the mechanisms of the neuroprotective action of AA-GABA and PGE2-GABA. Conclusion: For the first time, we demonstrated the ability of AA-GABA and its putative metabolite COX-2 PGE2-GABA to improve cerebral circulation, attenuate structural damage and lipofuscin accumulation during cerebral ischemia. The natural origin of AA-GABA, which possesses neuroprotective and cerebrovascular activity, as well as anti-aggregatory activity, allows considering AA-GABA as one of the endogenous protective factors in ischemic brain lesions. Graphical abstract: HTML XML PDF
      PubDate: Tue, 21 Sep 2021 12:03:23 +030
       
  • Effect of adjuvant drugs on the analgesic activity of opioid morphine
           analgesics and compound RU-1205

    • Abstract: Research Results in Pharmacology 7(3): 41-47
      DOI : 10.3897/rrpharmacology.7.68025
      Authors : Alexander A. Spasov, Olesya Iu. Grechko, Natalya V. Eliseeva, Yuliya V. Lifanova, Angelina N. Aleksandrenkova : Introduction: Adjuvant medications can be used to increase the analgesic effect of opioid analgesics, reduce the manifestation of side effects, and also for premedication. This paper provides information on the effect of clonidine, haloperidol, metocloparmide, diazepam, midazolam on opioid analgesics: - morphine and the selective kappa-opioid agonist compound RU-1205. Materials and methods: A probable interaction between RU-1205, morphine and adjuvant drugs in pain behaviors was carried out on the model of somatogenic pain. 95 male mice received either RU-1205 (5 mg/kg, i.p.) and morphine (1 mg/kg, i.p.) separately or in combination with haloperidol (0.45 mg/kg, i.p.); midazolam (0.3 mg/kg, i.p.); diazepam (1 mg/kg, i.p.); metoclopramide (5 mg/kg, i.p.), and clonidine (1 mg/kg, i.p.). The analgesic effect was assessed by tail flick test. Registration of the latent period of the reaction was carried out 30, 60 and 90 minutes after the adjuvant drug administration. Results: When studying the interaction with morphine, it was found that clonidine, haloperidol and metoclopramide enhanced the effects; diazepam offset them, and midazolam had no affect on the analgesic properties. In the course of the studies, RU-1205 showed an increase in analgesic activity when combined with clonidine, a slight increase with midazolam, and a decrease when co-administered with diazepam. Haloperidol had no influence on the effect of RU-1205, while metoclopramide both potentiated and reduced the analgesic effect. Discussion: Pharmacodynamic and pharmacokinetic interactions of RU-1205 with an α2AR agonist, benzodiazepine receptor agonists, D2P antagonist, and σ-receptor blocker were established. Conclusion: The presented data make it possible to more accurately formulate ideas about the localization and action mechanism of the kappa-agonist of opioid receptors, the compound RU-1205. HTML XML PDF
      PubDate: Tue, 21 Sep 2021 08:00:01 +030
       
  • Transgenic mice Cre-dependently expressing mutant polymerase-gamma: novel
           test-system for pharmacological study of mitoprotective drugs

    • Abstract: Research Results in Pharmacology 7(3): 33-39
      DOI : 10.3897/rrpharmacology.7.72784
      Authors : Marina V. Kubekina, Yulia Yu. Silaeva, Alexandra V. Bruter, Diana S. Korshunova, Leonid A. Ilchuk, Yulia D. Okulova, Mariya O. Soldatova, Evgeniya Seryogina, Inga M. Kolesnik, Polina A. Ukolova, Mikhail V. Korokin, Alexey V. Deykin : Introduction: PolG-alpha is a nuclear-encoded enzyme which provides replication and repair of mitochondrial DNA. D257A mutation of PolG-alpha leads to change in the N-terminal ”proofreading” domain, which deprives the enzyme of 3′-5′ exonuclease activity, resulting in accumulation of mutations in the mitochondrial genome. Materials and methods: Murine zygotes were microinjected with transgene construction carrying mutant murine Polg coding sequence and GFP coding sequence by a loxP-flanked STOP-cassette. Two Cre-activator strains, CMV-Cre (systemic activation) and Tie2-Cre (endothelial activation), were used for activation of the transgene. To confirm the insertion and Cre-dependent activation of the transgene, genotyping and qPCR copy number measurement of mutant Polg were performed, and GFP fluorescence was assessed. Results: Two primary transgenic animals were used as the founders for two lines with copy numbers of transgene ~7 and ~5. After systemic activation, the number of the transgene copies decreases to ~1.0 while endothelial specific activation does not affect the number of transgene copies in tail tissue. Discussion: A murine model with spatial control of mutant Polg expression has been developed. To our knowledge, this is the first transgenic model of tissue-specific mitochondrial dysfunction. Conclusion: Transgenic mice Cre-dependent expressing mutant polymerase-gamma are a novel test-system for studying mitochondrial biology and efficacy of mitoprotective drugs. HTML XML PDF
      PubDate: Fri, 17 Sep 2021 12:35:03 +030
       
  • Ubiquinol ameliorates endothelial dysfunction and increases expression of
           miRNA-34a in a rat model of pulmonary hypertension

    • Abstract: Research Results in Pharmacology 7(3): 23-31
      DOI : 10.3897/rrpharmacology.7.67291
      Authors : Tatyana A. Kuropatkina, Nadezda V. Pankova, Natalia A. Medvedeva, Oleg S. Medvedev : Introduction: In this research, we evaluate the effect of intravenously administrated solubilized ubiquinol on 4-week monocrotalin-induced pulmonary hypertension (PH) in rats. Materials and methods: To reproduce the model, some male Wistar rats were subcutaneously injected with alcohol solution of monocrotaline 60 mg/kg and the rest – with alcohol solution (Control). Those with monocrotaline (MCT) were divided into 3 groups. They underwent intravenous administration of 1% ubiquinol solution 30 mg/kg (MCT-Ubiquinol), the vehicle (MCT-Vehicle) and saline (MCT-saline) three times on days 7, 14 and 21, depending on the group. The hemodynamic parameters were measured in anesthetized rats on day 29. Right ventricle hypertrophy, pulmonary arteries reactivity and expression of miRNA-21 and miRNA-34a were estimated after euthanasia. Results and discussion: All MCT-groups demonstrated an increase in right ventricle systolic pressure and hypertrophy in comparison with the control group. An increase in lung weight was shown in MCT-Vehicle and MCT-Saline; however, the MCT-Ubiquinol indicators did not differ from those of the Control. There was an increased vasodilatation response to acetylcholine at concentrations of 1*10-6M and 1*10-5M in MCT-Ubiquinol in contrast to the other two MCT-groups. A significantly lower level of expression of miRNA-34a was observed in MCT-Ubiquinol. Conclusion: Our findings suggest that a triple ubiquinol injection influences pulmonary changes and endothelium-depended vasodilatation, which contributes to pulmonary vascular tone and reactivity. A decrease in miRNA-34a expression in MCT-Ubiquinol group demonstrates the ubiquinol anti-inflammatory properties. HTML XML PDF
      PubDate: Mon, 13 Sep 2021 10:47:35 +030
       
  • Antiamnestic effect of new nicotinic acid derivatives

    • Abstract: Research Results in Pharmacology 7(3): 15-22
      DOI : 10.3897/rrpharmacology.7.68001
      Authors : Victor V. Yasnetsov, Diana E. Kaurova, Sofia Ya. Skachilova, Evgeniy Yu. Bersenev : Introduction: The search for new drugs for the prevention and treatment of vascular cognitive disorders continues to be a relevant task of pharmacology. In this regard, the aim of this work is to study the antiamnestic effect of five new nicotinic acid derivatives in comparison with the well-known drug mexidol (ethylmethylhydroxypyridine succinate) in animals. Materials and methods: The experiments were carried out on white male mice using conditioned passive avoidance reflex (CPAR). Electroconvulsive shock (ECS), scopolamine administration, and acute hypoxia in a hermetic chamber were used as amnesic effects. Testing for the safety of CPAR was performed 24 h after amnesic exposure. The new substances, reference drug mexidol, and a 0.9% sodium chloride solution (control group) were administered once intraperitoneally 60 min before mice training. Results and discussion: Three of the five new nicotinic acid derivatives, LKhT 4-19 (100 mg/kg), LKhT 6-19 (25, 50, and 100 mg/kg), and LKhT 7-19 (100 mg/kg), have antiamnestic properties on models of amnesia in mice induced by ESC, scopolamine, and acute hypoxia in a hermetic chamber. At the same time, the most efficient substance – LKhT 6-19 – exceeds the reference drug mexidol on all three models used. In addition, this compound is also more efficient than two other new compounds, LKhT 4-19 and LKhT 7-19, on the model of ESC-induced amnesia and LKhT 7-19 on the scopolamine-induced amnesia model. Conclusion: Compound LKhT 6-19 is promising for further advanced preclinical studies as a potential drug with antiamnestic activity. Graphical abstract: HTML XML PDF
      PubDate: Tue, 7 Sep 2021 00:05:36 +0300
       
  • Nutritional supplementation of the pharmacotherapy of prostate diseases

    • Abstract: Research Results in Pharmacology 7(3): 1-14
      DOI : 10.3897/rrpharmacology.7.67465
      Authors : Oleg I. Bratchikov, Igor A. Tyuzikov, Pavel A. Dubonos : Introduction: Nutritional supplementation is an integral part of modern pharmacotherapeutic strategies for prostate diseases with different levels of evidence for specific nutrients. Provitamin A (beta-carotene), vitamin A (retinol) and prostate diseases. Their effects have not been sufficiently studied, and the available data are conflicting to recommend them as a nutritional supplement. Vitamin E (tocopherol) and prostate diseases. Its effects have not been sufficiently studied, and the available data are conflicting to recommend it as a nutritional supplement. Vitamin C (ascorbic acid) and prostate diseases. Its effects have not been sufficiently studied, and the available data are conflicted to recommend it as a nutritional supplement. Vitamin K and prostate diseases. Its effects have not been sufficiently studied, and the available data are conflicted to recommend it as a nutritional supplement. Vitamin D and prostate diseases. The evidence base of the vitamin D prostatotropic effects has been accumulated, which allows us to consider its deficiency replacement as an effective nutritional supplement in prostate diseases. Omega-3 PUFAs and prostate diseases. They have universal physiological effects; however, the evidence base for their recommendation as a nutritional supplement for prostate diseases is still insufficient. Zinc and prostate diseases. Positive effects of zinc on the prostate gland are known for a fact and allow us to recommend it as a nutritional supplement for prostate diseases. Selenium and prostate diseases. The reliably proven positive effects of selenium on the prostate gland allow us to recommend it as a nutritional supplement for prostate diseases. Magnesium and prostate diseases. Its effects have not been sufficiently studied, and the available data are conflicting to recommend it as a nutritional supplement. HTML XML PDF
      PubDate: Wed, 7 Jul 2021 11:07:30 +0300
       
  • Effect of the secretome of multipotent mesenchymal stromal cells induced
           by dexamethasone in vitro on the expression of phospho-NF-κB p65 and
           Ki-67 in mononuclear cells

    • Abstract: Research Results in Pharmacology 7(2): 101-107
      DOI : 10.3897/rrpharmacology.7.68533
      Authors : Polina A. Golubinskaya, Maksim V. Puzanov, Svetlana Y. Burda, Darya A. Kostina, Yuriy E. Burda : Introduction: To investigate the influence of secretomes from native and dexamethasone-treated adipose-derived multipotent mesenchymal stromal cells (MMSC) on the proliferation of mononuclear cells (MNCs) and on their expression of phospho-NF-κB p65 in vitro. Materials and Methods: MMSCs were isolated from the fat of 5 healthy donors. The cells were grown in culture up to passage four, then treated with dexamethasone for 3 hours, washed off the preparations, and incubated in a serum-free medium for 48 hours. Some of the cells were not treated with dexamethasone. Supernatants from cell cultures were concentrated by ultrafiltration, standardized by the content of galectin-1, sterilized, and added to MNCs from peripheral blood of 8 healthy donors. MNCs were isolated in a Ficoll density gradient according to a standard protocol. The expression of phospho-NF-κB p65 and Ki-67 in MNCs under the influence of MMSC secretomes in isotypic and negative controls was determined on a flow cytometer. Results and Discussion: The expression of phospho-NF-kκB p65 and Ki-67 is decreased by the MMSC secretome. At the same time, a statistically significant decrease in phospho-NF-κB p65 by 36.2% (p < 0.05) is observed when using a secretome from native cells. Ki-67 expression is reduced by 42.3% (p < 0.05) under the influence of a secretome from dexamethasone-treated MMSCs. Conclusion: The MMSC secretome, as well as MMSCs themselves, has an anti-inflammatory effect due to the effect on the expression of the active form of NF-κB and the proliferative activity of mononuclear cells. At the same time, pretreatment of cells with dexamethasone reduces the effect on phospho-NF-κB expression and increases the inhibitory effect on MNC proliferation. HTML XML PDF
      PubDate: Wed, 30 Jun 2021 00:41:35 +030
       
  • Distribution, excretion and metabolic pathways of a single parenteral
           administration of kappa-opioid receptor agonist RU-1205

    • Abstract: Research Results in Pharmacology 7(2): 59-65
      DOI : 10.3897/rrpharmacology.7.67261
      Authors : Alexander A. Spasov, Lyudmila A. Smirnova, Olesya Iu. Grechko, Natalya V. Eliseeva, Yuliya V. Lifanova, Andrey I. Rashchenko, Olga N. Zhukowskaia, Anatoly S. Morkovnik, Vera A. Anisimova, Olga E. Syrvacheva : Introduction: The purpose was to study the pharmacokinetic properties of RU-1205 with the previously identified kappa-agonistic and analgesic effects after parenteral administration. Materials and methods: Pharmacokinetic parameters of RU-1205 after intravenous and subcutaneous administration at doses of 10 mg/kg and 50 mg/kg, respectively, were investigated, using the method of high-performance liquid chromatography with measurement of the compound according to a pre-established calibration curve. The indices of the area under the pharmacokinetic curve, clearance, half-life, residence time of the drug molecule in the body, total (apparent) volume of distribution, as well as the indicator of absolute bioavailability for subcutaneous administration were calculated. Tissue distribution and excretion of RU-1205 were also studied. Evaluation of metabolism of RU-1205 was conducted in silico, using the PALLAS 3.00 software, with the use of specific tests with CYP 450 substrates and by studying the ability of RU-1205 to form conjugates with endogenous acids. Results and discussion: It was found that after a single intravenous administration, the investigated substance was determined in the blood for 12 h; the half-life was 8.49 hours. The absolute bioavailability after subcutaneous administration is 57.35%. RU-1205 is eliminated within 3–4 days. The main route of excretion is extrarenal. The biotransformation of the substance probably proceeds mainly with the formation of oxidized forms of the initial molecule according to the reactions of the first phase of metabolic transformation, so the chance to observe phase 2 of the metabolism could be very low. Conclusion: The test substance undergoes a long process of elimination, has the highest tropism to the elimination organs and undergoes active biotransformation processes in the body of animals. HTML XML PDF
      PubDate: Tue, 29 Jun 2021 14:05:05 +030
       
  • Activity of ROS-induced processes in the combined preconditioning with
           amtizol before and after cerebral ischemia in rats

    • Abstract: Research Results in Pharmacology 7(2): 49-57
      DOI : 10.3897/rrpharmacology.7.66808
      Authors : Olga S. Levchenkova, Vasiliy E. Novikov, Viktoriya V. Vorobyova, Konstantin N. Kulagin : Introduction: The dose-dependent effect of reactive oxygen species (ROS) in tissues in preconditioning (PreC) and oxidative stress, as well as NO-synthase participation in mitochondrial ROS production determined the study aim – to assess the impact of the neuroprotective method of combined preconditioning (CPreC) on free radical reactions (FRRs) in brain in normoxia and in cerebral ischemia, including in NO-synthase blockade. Materials and methods: The intensity of FRR by iron-induced chemiluminescence (CL), the content of lipid peroxidation products and antioxidant enzyme activity were investigated 1 hr (early period) and 48 hrs (delayed period) after CPreC (amtizol and hypobaric hypoxia) in Wistar rat brain. Some animal groups were operated (common carotid artery bilateral ligation) 1 hr and 48 hrs after CPreC, as well as with preliminary introduction of L-NAME and aminoguanidine. Results and discussion: In normoxia, CPreC led to increase the CL maximum level (Fmax) in the delayed PreC period. The amount of thiobarbituric acid reactive products (TBA-RP), activity of superoxide dismutase (SOD) and catalase in mitochondrial fraction of rat brain did not change in comparison with the intact control in both PreC periods. In cerebral ischemia, oxidative stress was observed. The CPreC use before ischemia caused a decrease in CL parameters and TBA-RP in brain, the maintenance of SOD and high catalase activity. NO-synthase inhibitors partially abolished the antioxidant effect of CPreC in ischemia. Conclusion: CPreC had no influence on FRRs in brain tissue in normoxia, but prevented their excessive activation after ischemia, especially in the delayed period. NO-synthase was involved in the CPreC neuroprotection. HTML XML PDF
      PubDate: Tue, 29 Jun 2021 13:58:25 +030
       
  • Migraine pharmacology and brain ischemia

    • Abstract: Research Results in Pharmacology 7(2): 67-82
      DOI : 10.3897/rrpharmacology.7.67463
      Authors : Ruben S. Mirzoyan, Tamara S. Gan’shina, Ilya N. Kurdyumov, Denis V. Maslennikov, Anna V. Gnezdilova, Alexander A. Gorbunov, Elena V. Kursa, Antonina I. Turilova, Leonid M. Kostochka, Narine R. Mirzoyan : Introduction: The aim of this review article was to analyze in details the mechanism of drugs’ effects in the treatment and prevention of a migraine attack, as well as to discuss the hypotheses of migraine pathogenesis. Migraine attack treatment agents: The main agents for migraine attack treatment have an anti-nociceptive activity. Agents for migraine preventive treatment: β-blocker propranolol also has anti-serotonin and analgesic activities, and most drugs used for the prophylactic treatment of migraine have a vasodilating activity. Vascular hypothesis of migraine pathogenesis: Despite numerous studies that have expanded our understanding of migraine pathogenesis, the importance of the vascular component in the pathogenesis of this disease has not questioned yet. Neurogenic hypotheses of cortical spreading depression: It is necessary to take into account the points of this hypothesis in the context of the pathophysiology of migraine. Neurochemical serotonin hypotheses of migraine pathogenesis: Serotonin plays an important role in the pathogenesis of migraine. Trigemino-vascular hypotheses of migraine pathogenesis: The trigemino-vascular hypothesis claims to solve the problem of migraine pain. Migraine and ischemic brain damage: Migraine is a risk factor for ischemic stroke and cognitive disorders. Search for the new anti-ischemic anti-migraine preparations: A methodology for the search for new anti-ischemic anti-serotonin drugs for the treatment of migraine is proposed. Conclusion: Belonging of a drug to one or another pharmacological group does not always correspond to its therapeutic effect on the pathogenetic processes of migraine. Migraine with its variety of forms cannot fit only one of the proposed hypotheses on the pathogenesis of this disease. Graphical abstract: HTML XML PDF
      PubDate: Tue, 29 Jun 2021 12:53:35 +030
       
  • Study to elucidate the pharmacological activity of retinalamin in a rat
           model of ischemic retinopathy

    • Abstract: Research Results in Pharmacology 7(2): 39-48
      DOI : 10.3897/rrpharmacology.7.67390
      Authors : Anna Pobeda, Anna Kalatanova, Daria Abasheva, Aleksandr Dolzhikov, Nikolai Solovev, Kristina Shchurovskaya, Sofia Chernyaeva, Inga M. Kolesnik : Introduction: Over the past few years, the incidence of retinal ischemic disorders has been increasing, due to a rising prevalence of such socially burdensome diseases as diabetes and hypertension, which ultimately lead to ocular vascular pathology. The identification of new treatment options that would prevent retinal neuron death is a crucial task of modern pharmacology. Materials and methods: The research was carried out on male Wistar rats. Retinopathy was modeled by inducing a 30-min ischemic episode, with a 72-hour period of reperfusion and subsequent administration of Retinalamin and Emoxypine for 10 days. The effectiveness of the drugs was evaluated by electroretinographic, ophthalmoscopic and morphological assessments. Results and discussion: On Day 14 of the experiment, a dose-dependent preservation of the electroretinogram b-wave/a-wave amplitude ratio was observed in the animals treated with Retinalamin depending on a dose (1.39±0.06, 1.46±0.03 and 1.49±0.04 in low (0.214 mg/kg), medium (0.428 mg/kg) and high (0.857 mg/kg) Retinalamin dose groups, respectively). The ophthalmoscopic picture of the fundus oculi also improved following the treatment with Retinalamin (1.42, 1.69 and 1.90 times lower ophthalmoscopic scores compared to placebo-treated animals in low, medium and high dose groups, respectively). The morphologic “coefficient of change” applied to ganglion cell layer was 2.2, 1.7 and 1.6 points in low, medium and high dose Retinalamin groups, respectively. These results are significantly different from both intact and placebo group (p
      PubDate: Tue, 29 Jun 2021 12:06:45 +030
       
  • Proteins of allogeneic hepatocytes and pharmacological preparations for
           the correction of immunometabolic disorders in experimental liver
           pathology

    • Abstract: Research Results in Pharmacology 7(2): 83-99
      DOI : 10.3897/rrpharmacology.7.70314
      Authors : Ekaterina S. Litvinova, Nikolay N. Konoplya, Anastasiya A. Shulginova, Anastasiya V. Kharchenko : Introduction: The relationship of numerous metabolic shifts, disorders of hepatocytes functional activity resulting from hypoxia and toxic liver damage with the function of the immune system has not been sufficiently studied so far, nor have the most effective methods of pharmacological correction been established. Materials and Methods: The studies were carried out on 603 mature male Wistar rats and 45 mice. Acute toxic liver damage (ATLD) was modeled by intramuscular introduction of carbon tetrachloride; acute liver ischemia (ALI) was caused by clamping the hepatoduodenal ligament for 20 minutes; chronic alcohol intoxication (CAI) was modeled by forced intragastric administration of 20% ethanol solution for 60 days. Isolation of xenogeneic (murine) and allogeneic (rat) hepatocytes from newborn mice and rats was carried out according to the method of Berry and Friend (1969); culture fluid of hepatocytes and its protein fractions were prepared according to our developed techniques. The obtained biological material was intraperitoneally introduced into the rats with ATLD, ALI, and CAI. Results and Discussion: In all the models of the liver damage, there developed morphological and biochemical signs of the liver damage, impaired congenital and adaptive immunity, oxidative stress, increased lipid peroxidation processes. Conclusion: The introduction of allogeneic hepatocytes, culture fluid obtained on their basis,and proteins isolated from it with MW less than 130 kDa to the recipients with toxic and ischemic liver damage more effectively corrects the pathologic changes in the liver in comparison with xenogeneic hepatocytes, their culture fluid and pharmacological preparations (combinations of Essentiale N and Hypoxenum or Heptral and Mexicor). HTML XML PDF
      PubDate: Tue, 29 Jun 2021 11:43:40 +030
       
  • In vivo study of pharmacokinetic parameters of a new combination drug
           based on citicoline and memantine

    • Abstract: Research Results in Pharmacology 7(2): 23-30
      DOI : 10.3897/rrpharmacology.7.60380
      Authors : Boris B. Sysuev, Damir K. Salakhetdinov : Introduction: Cognitive impairment (dementia) is one of the most common pathologies with increasing numbers of patients. Most often they are the symptoms of Alzheimer’s disease and vascular brain diseases, for which such drugs as memantine and citicoline are used. The development of a combination drug with these active pharmaceutical ingredients can significantly increase the effectiveness of therapy. Materials and methods: The pharmacokinetics of memantine and citicoline combination drug was evaluated in comparison with the marketed drugs (reference drugs) of these pharmaceutical substances approved for medical use by determining their content in blood plasma of experimental animals after a single oral administration. Results: Seventy-two hours after the administration of memantine drug, about 5% and 17% of the maximum concentration of memantine released from Akatinol Memantine and the developed combination drug were found in blood plasma, respectively. By the 120th hour after the beginning of the experiment, no memantine was detected in blood plasma of any animal. By the 24th hour after the beginning of the experiment, about 46% and 50% of the maximum concentration of citicoline released from the developed combination drug and the Ceraxon drug were found in blood plasma of the rabbits, respectively. Discussion: It was detected that the amounts of released memantine and citicoline from the developed combination drug exceeded the amounts of the appropriate pharmaceutical substances released from the reference drugs. The bioavailability of these substances from the developed combination drug was higher than from the marketed mono formulations used as reference drugs. Conclusion: Based on the obtained results of memantine and citicoline concentrations in bioassays, the main pharmacokinetic parameters of the studied preparations were calculated, the results of which showed the superiority of the developed combination drug over the reference drugs. HTML XML PDF
      PubDate: Tue, 15 Jun 2021 16:31:14 +030
       
  • Screening of anxiolytic properties and analysis of structure-activity
           relationship of new derivatives of
           6-(4-methoxy)-7H-[1,2,4]triazolo[3,4-a][2,3]benzodiazepine under the code
           RD

    • Abstract: Research Results in Pharmacology 7(2): 31-37
      DOI : 10.3897/rrpharmacology.7.67499
      Authors : Maria O. Skripka, Alexander A. Spasov, Dmitriy V. Maltsev, Mikhail V. Miroshnikov, Dmitriy S. Yakovlev, Kira T. Sultanova, Maxim A. Kochergin, Lyudmila N. Divaeva : Introduction: Searching for new compounds with anti-anxiety activity resulting from the combination of privileged scaffolds is a promising direction in medicinal chemistry and in the development of new drugs. Anxiolytic potential and cytotoxic properties of previously synthesized molecules, containing fragments of 2,3-benzodiazepine and 1,2,4-triazole – 6-(4-methoxyphenyl)-7H-[1,2,4]triazolo[3,4-A][2,3]benzodiazepines under the generic code RD were studied. Materials and methods: Screening for anxiolytic activity was performed on elevated plus maze (EPM) and open field (OF) test models. Structural and functional analysis of the anti-anxiety activity of the studied substances was carried out. A degree of muscle relaxant effect of the substances was assessed in the tests Grid, Wire, and Rotarod. A cytotoxicity study of RD compounds was carried out using an MTT assay on human hepatocellular carcinoma cells HepG2. Results and discussion: For a number of novel triazolo[3,4-a][2,3]benzodiazepine derivatives, a prominent anxiolytic activity was manifested in terms of EPM test. The results of OF test were consistent with the obtained data and confirmed the presence of the sought activity in the leading compounds. There was no significant effect on muscle tone for the compounds under study. It was observed that RD compounds possessed no cytotoxic properties and were safe for further studies in vivo. Conclusion: Among the new derivatives of 6-(4-methoxyphenyl)-7H-[1,2,4]triazolo[3,4-a][2,3]benzodiazepine under the code RD, substances (RD-4, 12, 13) with a high anxiolytic activity comparable to diazepam and tofisopam were found. The most promising compound is RD-4 due to its pronounced anxiolytic and low cytotoxic properties. HTML XML PDF
      PubDate: Tue, 15 Jun 2021 13:29:40 +030
       
  • Mafusol and its combination with REXOD as correctors of reduced blood
           circulation in the skin associated with normoglycemia or diabetes mellitus
           complicated by exogenous hypercholesterolemia

    • Abstract: Research Results in Pharmacology 7(2): 1-14
      DOI : 10.3897/rrpharmacology.7.54319
      Authors : Olga N. Gulevskaya, Pavel A. Galenko-Yaroshevsky, Svetlana A. Lebedeva, Galina V. Sukoyan, Ivan I. Pavlyuchenko, Anait V. Zelenskaya, Alexandr V. Uvarov, Kristina V. Tseluiko, Viktor L. Popkov, Andrey V. Zadorozhniy, Elena N. Chuyan, Marina Yu. Ravaeva, Pavel A. Galenko-Yaroshevsky Jr : Introduction: The search for and development of new highly active medications and their combinations of the appropriate direction of action remains an urgent problem due to the complications of diabetes mellitus, especially burdened with atherosclerosis, including skin and vascular lesions. Materials and methods: The acute toxicity, histoprotective and dermatoprotective effects of mafusol, rexod, alprostadil and their combinations were studied in male rats with normoglycemia and alloxan diabetes complicated by exogenous hypercholesterolemia. Results: The combination of mafusol with rexod is less toxic than mafusol. In arteriovenous insufficiency of the tail, ischemia of the skin fold and skin flap, mafusol (6.25, 12.5 and 25.0 mg/kg in terms of fumarate), rexod (0.01 and 0.02 mg/kg) and especially their combination (6.25 and 0.01 mg/kg) have significant histoprotective, dermatoprotective, hypoglycemic and lipid-lowering effects, both in normoglycemia and alloxan diabetes complicated by exogenous hypercholesterolemia. Alprostadil (10 mg/kg) and especially its combination with mafusol (6.25 mg/kg) have a dermatoprotective effect. Discussion: Rexod reduces the acute toxicity of mafusol. The dermatoprotective effect of mafusol, rexod and, to a greater extent, their combination may be associated with increased microhemocirculation, antihypoxic properties and activation of energy processes in the skin, normalization of carbohydrate and lipid metabolism in alloxan diabetes, complicated by exogenous hypercholesterolemia, increased reserve capacity of the antioxidant system, and possibly with the ability of mafusol and rexod to reduce blood viscosity and improve rheological properties of the blood. The combination of mafusol with alprostadil increases the dermatoprotective activity of the latter. Conclusion: Combinations of mafusol with rexod and alprostadil can be recommended for clinical study as dermatoprotective agents for treating traumatic injuries and diabetes mellitus complicated by atherosclerosis. HTML XML PDF
      PubDate: Fri, 28 May 2021 11:33:07 +030
       
  • Features of the immune status in patients with chronic and complicated
           pyodermas: choice of a therapeutic correction method

    • Abstract: Research Results in Pharmacology 7(2): 15-21
      DOI : 10.3897/rrpharmacology.7.68557
      Authors : Roman A. Khmel’nitskij, Andrej V. Vislobokov, Pavel V. Kalutskii : Introduction: To compare the features of the immune status in patients with chronic and complicated pyoderma in the course of complex pharmacotherapy using immunomodulators based on transfer factors and glucosaminylmuramyldipeptide. Materials and methods: A clinical examination of 107 patients with pyoderma, divided into three groups, was carried out. All individuals underwent immunological examination before and after etiopathogenetic treatment. The patients of the first group were additionally treated with a drug containing signaling immunoactive molecules (transfer factor) as an immunomodulator; the patients of the second group received glucosaminylmuramyldipeptide; and the patients of the third group received standard antibacterial therapy. Results and discussion: Prior to the beginning of pathogenetic therapy, the patients were found to lack non-specific mechanisms of antimicrobial protection; there was a decrease in the activity and intensity of phagocytosis: phagocytic index and phagocytic number of neutrophils by 1.2 and 1.3 times; the production of proinflammatory cytokines IL-6 increased by 2.3 times, IL-8 –by 2.1 times, and TNFa – by 2.4 times. The study of immunological parameters after the inclusion of immunomodulators into the therapy revealed an increase in the phagocytic activity of neutrophils, and the indicators of the NST test were close to the control ones. The production of proinflammatory cytokines in the blood serum was restored to the level of the healthy individuals. Normalization of the number of CD4+-, CD8+-, CD19+-cells was observed in 86.0 ± 3% of the patients. At the same time, against the background of the use of glucosaminylmuramyldipeptide, a more intensive recovery of all links of anti-infectious immunity was recorded in comparison with the group where transfer factor molecules were used. Conclusion: A drug based on glucosaminylmuramyldipeptide can be recommended as the drug of choice in non-specific immunocorrection for complex pharmacotherapy of pyoderma accompanied by secondary immune insufficiency, in comparison with a drug containing transfer factors. HTML XML PDF
      PubDate: Fri, 28 May 2021 11:20:14 +030
       
  • Development of a risk-oriented algorithm for the combined use of
           hemostatics and anticoagulants to prevent thrombosis and bleeding cases
           after total arthroplasty of knee or hip joints

    • Abstract: Research Results in Pharmacology 7(1): 65-74
      DOI : 10.3897/rrpharmacology.7.65708
      Authors : Lilia S. Golovko, Andrey V. Safronenko, Elena V. Gantsgorn, Nataliya V. Sukhorukova, Andrey V. Kapliev : Introduction: The goal of our study was to develop a risk-oriented algorithm for the combined use of hemostatics and anticoagulants in patients after total arthroplasty of the knee or hip joints to reduce the risk of thrombohemorrhagic complications. Materials and methods: We performed a retrospective study (n=253). In group (Gr.) 1, the time interval (TI) between the administration of hemostatic and anticoagulant prophylaxis was ≤17 hours (n=145; 57.31%), and in Gr. 2 – 18-24 hours (n=108; 42.68%). We analyzed the influence of different factors on the development of thrombosis and bleeding cases after the operation. Results and discussion: Thrombohemorrhagic complications were observed in 27 (10.67%) patients. Thrombosis in Gr. 1 was associated with the use of tranexamic acid, and were recorded 2.2 times more often than in Gr. 2 (p75 years, for women – an initially low level of international normalized ratio, and activated partial thromboplastin time (APTT) (p75 years, among men and women – an increased preoperative level of APTT, for women – a decreased level of fibrinogen and platelets (p
      PubDate: Wed, 31 Mar 2021 21:58:19 +030
       
  • 3D organotypic cell structures for drug development and Microorganism-Host
           interaction research

    • Abstract: Research Results in Pharmacology 7(1): 47-64
      DOI : 10.3897/rrpharmacology.7.62118
      Authors : Ekaterina V. Zubareva, Sergey V. Nadezhdin, Natalia A. Nadezhdina, Veronika S. Belyaeva, Yuriy E. Burda, Tatyana V. Avtina, Oleg S. Gudyrev, Inga M. Kolesnik, Svetlana Yu. Kulikova, Mikhail O. Mishenin : Introduction: The article describes a new method of tissue engineering, which is based on the use of three-dimensional multicellular constructs consisting of stem cells that mimic the native tissue in vivo – organoids. 3D cell cultures: The currently existing model systems of three-dimensional cultures are described. Characteristics of organoids and strategies for their culturing: The main approaches to the fabrication of 3D cell constructs using pluripotent (embryonic and induced) stem cells or adult stem cells are described. Brain organoids (Cerebral organoids): Organoids of the brain, which are used to study the development of the human brain, are characterized, with the description of biology of generating region-specific cerebral organoids. Lung organoids: Approaches to the generation of lung organoids are described, by means of pluripotent stem cells and lung tissue cell lines. Liver organoids: The features of differentiation of stem cells into hepatocyte-like cells and the creation of 3D hepatic organoids are characterized. Intestinal organoids: The formation of small intestine organoids from stem cells is described. Osteochondral organoids: Fabrication of osteochondral organoids is characterised. Use of organoids as test systems for drugs screening: The information on drug screening using organoids is provided. Using organoids to model infectious diseases and study adaptive responses of microorganisms when interacting with the host: The use of organoids for modeling infectious diseases and studying the adaptive responses of microorganisms when interacting with the host organism is described. Conclusion: The creation of three-dimensional cell structures that reproduce the structural and functional characteristics of tissue in vivo, makes it possible to study the biology of the body’s development, the features of intercellular interactions, screening drugs and co-cultivating with viruses, bacteria and parasites. HTML XML PDF
      PubDate: Wed, 31 Mar 2021 13:22:56 +030
       
  • N-acetylcysteine relieves neurologic signs of acute ethanol hangover in
           rats

    • Abstract: Research Results in Pharmacology 7(1): 75-83
      DOI : 10.3897/rrpharmacology.7.62622
      Authors : Denis V. Kurkin, Evgeny I. Morkovin, Nazar A. Osadchenko, Dmitry A. Bakulin, Marina A. Dubrovina, Yulia V. Gorbunova, Elizaveta E. Abrosimova, Vladislav E. Pustynnikov, Ivan N. Tyurenkov, Vladimir I. Petrov : Introduction: Alcohol abuse is one of the grave social and medical problems in many countries, including Russia. Alcohol not only negatively affects health, social and family relationships, but also a person’s performance. Hangover, which is a one of the negative consequences of alcohol intake, is a complex of neurological and somatic symptoms that occur when ethanol is almost completely metabolized to acetaldehyde. This condition, despite the severity and potential economic damage, remains poorly understood, and there are no effective medicines to treat it. Aim: to provide an experimental basis for the possibility of using N-acetylcysteine (NAC), a precursor of glutathione, as a medicine for prevention of the neurological and cognitive impairments due to alcohol intoxication. Materials and Methods: The study used male Wistar rats, which were intraperitoneally injected with ethanol at a dose of 3 g/kg to simulate acute ethanol intoxication. Sixty minutes before the injection, the animals from the experimental groups were gavaged with NAC (1 g/kg) or with an equivalent volume of saline. Immediately after awakening and 3 h after it, the animals were assessed for neurological deficits, motor skills, spontaneous motor activity, and cognitive functions. After the completion of the behavioral tests, the animals were euthanized to assess the level of glutathione, triglycerides (TGs), and malonic dialdehyde (MDA) in liver homogenates, and to determine the activity of enzymatic antioxidant systems and serum aminotransferases. Results and Discussion: The ethanol intoxication in the animals from the control group was associated with pronounced signs of neurological and cognitive impairments, including low spontaneous motor and exploratory activity, impaired fine motor skills in the adhesive test, and cognitive function decline in the Morris water maze test. The rats which had received NAC before ethanol injection demonstrated better fine motor skills in the adhesive test, a higher level of spontaneous motor activity and better performance in the Morris water maze test (in comparison to the animals treated with saline before alcohol intoxication). In the animals which had received NAC, the levels of glutathione, MDA, and TGs, as well as the activity of liver antioxidant enzymes, were closer to the values of the intact rats to a greater extent than in the animals that had been injected with ethanol and received saline. Conclusion: Orally administered NAC before acute ethanol intoxication led to a decrease in the severity of neurological deficiency in rats and reduced the amnesic effect of ethanol. This could be due to an improvement of ethanol metabolism and a decrease in the severity of disorders associated with oxidative stress and liver dysfunction. HTML XML PDF
      PubDate: Wed, 31 Mar 2021 01:36:11 +030
       
  • Changes in the respiratory function of the heart and brain mitochondria of
           animals after chronic alcohol intoxication affected by a new GABA
           derivative

    • Abstract: Research Results in Pharmacology 7(1): 33-40
      DOI : 10.3897/rrpharmacology.7.60469
      Authors : Tamara A. Popova, Margarita V. Kustova, Gulnara Kh. Khusainova, Valentina N. Perfilova, Igor I. Prokofiev, Yulia A. Smolnyakova, Ludmila E. Borodkina, Ivan N. Tyurenkov, Oleg V. Ostrovskiy, Olga S. Vasil’eva : Introduction: Chronic ethanol consumption leads to significant functional and structural changes in the mitochondria of the heart and brain, increasing generation of reactive oxygen species. Therefore, the search for substances, which improve the functional state of the mitochondria and, meantime, reduce the oxidative stress, is relevant. Materials and methods: 10-months-old Wistar female rats were used in the experiments. Chronic alcohol intoxication (CAI) was modelled by replacing drinking water with a 10% ethanol solution containing sucrose (50 g/L) for 24 weeks. Four groups were formed: 1 – intact animals; 2 – animals after chronic alcohol consumption; 3 – rats after CAI which were administered RSPU-260 (25 mg/kg); 4 – rats after CAI which were administered the reference drug Mildronate (50 mg/kg). The intensity of lipid peroxidation (LPO) and the rate of oxygen consumption in various metabolic states were determined. Results and discussion: Administration of the compound RSPU-260 to the animals exposed to alcohol over a long period of time resulted in an increase in both the rate of oxygen consumption (state 3) and the respiratory control ratio (RCR) of the mitochondria of heart and brain cells. The use of a GABA derivative promoted a decrease in malonic dialdehyde in the mitochondria of the heart and brain. Total SOD activity in the mitochondria of heart cells was significantly increased in the groups of rats treated with RSPU-260. In terms of efficiency, the compound RSPU-260 was comparable to the reference drug Mildronate. Conclusions: The compound RSPU-260, and the reference drug Mildronate improve mitochondrial oxidative phosphorylation in heart and brain cells, the functioning of antioxidant enzymes in animals after CAI, and can be used to correct alcoholic damage to these organs. HTML XML PDF
      PubDate: Tue, 23 Mar 2021 13:21:44 +020
       
  • In search of new brain biomarkers of stress

    • Abstract: Research Results in Pharmacology 7(1): 41-46
      DOI : 10.3897/rrpharmacology.7.63326
      Authors : Petr D. Shabanov, Aleksandra A. Blazhenko, Aleksandr S. Devyashin, Platon P. Khokhlov, Andrei A. Lebedev : The aim: of the study was to investigate the level of ghrelin in various brain structures during a stress response in Zebrafish to a predator, to evaluate this indicator as a potential biomarker of stress, and the effect of a benzodiazepine tranquilizer (phenazepam) on stress-induced changes Materials and methods: The object of the study was Zebrafish, or Danio rerio wild type, which was subjected to stress by exposure to a predator Hypsophrys nicaraguensis from the cichlid family. In the tail tissue, the level of cortisol was determined, in the brain – the level of total (acylated and non-acylated) ghrelin by the method of enzyme-linked immunosorbent assay. The benzodiazepine anxiolytic phenazepam (1 mg/L), a ghrelin antagonist [D-Lys3]-GHRP-6 (0.333 mg/l) and corticotropin-releasing hormone (CRF; 0.4 mg/L) were used as the pharmacological agents. Results and discussion: Exposure to a predator, just as administering CRF, more than doubled the level of cortisol in the tail tissue. [D-Lys3]-GHRP-6 and phenazepam prevented an increase in a tissue cortisol level. Simultaneously, in the medulla oblongata and cerebellum, the phylogenetically most ancient structures, rather than in the forebrain (telencephalon) or in the midbrain (corpora bigemia), the level of ghrelin was recorded about 500 pg/g of total protein. In response to exposure to a predator, the level of ghrelin increased in the forebrain and midbrain to nanogram concentrations and moderately decreased in the cerebellum. The effect was prevented by phenazepam and [D-Lys3]-GHRP-6. Conclusion: Increases in ghrelin in the brain in response to stressful situations can be seen as a functional brain biomarker of stress, along with increased levels of tissue cortisol levels. Both of these effects are prevented by both the ghrelin antagonist and the benzodiazepine tranquilizer. The mechanism of action of the tranquilizer is a functional antagonism between the GABAergic system of the brain and the ghrelin system. HTML XML PDF
      PubDate: Tue, 23 Mar 2021 12:41:27 +020
       
  • ACTH6-9-PGP improves memory consolidation processes in rats

    • Abstract: Research Results in Pharmacology 7(1): 27-32
      DOI : 10.3897/rrpharmacology.7.62479
      Authors : Svetlana A. Dodonova, IgorIgor’ I. Bobyntsev, Andrey E. Belykh, Anton O. Vorvul’ : Introduction: The His-Phe-Arg-Trp sequence corresponding to the 6-9th amino acid residue of the adrenocorticotropic hormone molecule (ACTH6-9) is the critical pharmacophore of all endogenous melanocortin receptor agonists. In order to effects prolongation it may be stabilized by the addition of the amino acid sequence Pro-Gly-Pro (PGP) to the C-terminus. The aim of this work was to study the effect of ACTH6-9-PGP (HFRWPGP) on the processes of memory consolidation in the model of passive avoidance conditioning in comparison with ACTH4-7-PGP effects. Materials and methods: The study was carried out on the model of passive avoidance conditioning. The effects of ACTH6-9-PGP were studied after its intraperitoneal injection to male Wistar rats at doses of 0.5, 5, 50, 150, and 450 μg/kg 15 minutes before the experiment, whereas the effects of ACTH4-7-PGP– under the similar conditions at doses of 50, 150, and 450 μg/kg. Results and discussion: It was found that ACTH6-9-PGP had a pronounced stimulating effect on the memory consolidation process in the dose range from 0.5 μg/kg to 150 μg/kg, significantly increasing the latent period of an animal entering the dark chamber. Administration of ACTH4-7-PGP led to an improvement in the consolidation processes of the acquired conditioned reflex at the doses of 50 μg/kg and 450 μg/kg. Conclusion: The range of effective doses of ACTH6-9-PGP is lower than that of ACTH4-7-PGP, which indicates the greater activity of HFRWPGP sequence in relation to memory consolidation processes and allows considering this peptide as a promising molecule for creating nootropic pharmacological drugs. HTML XML PDF
      PubDate: Tue, 9 Mar 2021 21:59:13 +0200
       
  • Experimental assessment of immunoreactivity indices and effectiveness of
           pharmacotherapy schemes in surgical models of acute pancreatitis of
           various severity

    • Abstract: Research Results in Pharmacology 7(1): 21-26
      DOI : 10.3897/rrpharmacology.7.63473
      Authors : Viktor A. Lazarenko, Petr M. Nazarenko, Pavel K. Mikaelyan, Dmitrii P. Nazarenko, Alexey L. Loktionov : Introduction: The investigation was aimed at assessment of immunoreactivity in the experimental groups of animals and evaluation of effectiveness of different combinations of pharmacological drugs used in the surgical models for the treatment of acute pancreatitis (AP) of various degrees of severity. Materials and methods: As an object of research, sexually mature male individuals of mongrel white rats were used. Acute pancreatitis of various degrees of severity was caused by either a separate or simultaneous ligation of the pancreas ducts and an intraductal injection of the 50% bile solution in a dose of 0.2 mg/kg. Correction of immunoreactivity indices in the experimental animals was performed with the use of drug combinations producing immunomodulating, antioxidant and membrane protecting effects. Evaluation of the dynamics of immune parameters in rats was carried out using test systems from various manufacturers for laboratory analysis. The obtained findings were statistically processed with descriptive and variation techniques. Results and discussion: The rats developed AP of various degrees of severity, and differently expressed shifts in immunoreactivity indices were observed. Assessment of immune and oxidant indices in experimentally induced acute pancreatitis of moderate and severe states revealed metabolic and immune disorders with anti-inflammatory effects which had various degrees of expression. Combination of immunomodulators, antioxidants and membranoprotectors exerted positive effects on the immunoreactivity state, but insignificantly decreased the mortality rate in the groups of experimental animals. Conclusion: The combination of ferrovir, mexidol, phosphogliv, and its use for moderate and severe degrees of experimentally induced pancreatitis in rats decreases their mortality up to 12.9% and 19.8%. The combination of polyoxidonium, emoxipin and essentiale N exhibits positive clinico-laboratory effectiveness and lowers the mortality indices to statistically significant parameters – 11.8% и 19.6%, correspondingly, with p < 0.05. HTML XML PDF
      PubDate: Fri, 12 Feb 2021 22:23:06 +020
       
  • Renoprotective effect of carbamylated darbepoetin and udenafil in
           ischemia-reperfusion of rat kidney due to the effect of preconditioning
           and inhibition of nuclear factor kappa B

    • Abstract: Research Results in Pharmacology 7(1): 1-19
      DOI : 10.3897/rrpharmacology.7.63059
      Authors : Darya A. Kostina, Tatiana G. Pokrovskaya, Vladimir Y. Poltev : Introduction: Acute kidney injury is a widespread complication in hospitalized patients, with a high mortality rate and long-term complications affecting prognosis and quality of life and with high human and financial costs. In addition, to date, no clear algorithm for the prevention of this type of damage has been developed. Materials and methods: The research was carried out on male Wistar rats. A 40-minute renal ischemia-reperfusion model was used to model acute kidney injury. Further, the renoprotective properties of carbamylated darbepoetin, udenafil and their combination were assessed based on the analysis of the biochemical studies’ results, dynamics of the renal status and the renal microvasculature, and the pathomorphological picture. A series of experiments was also carried out to assess the contribution of adenosine triphosphate-dependent potassium channels and nuclear factor kappa B to the renoprotective properties of the said agents. Results and discussion: Prophylactic administration of carbamylated darbepoetin at a dose of 50 µg/kg and udenafil at a dose of 8.7 mg/kg led to a statistically significant decrease in creatinine and blood urea nitrogen, an increase in glomerular filtration rate with a simultaneous decrease in fractional excretion of sodium, as well as an increase in the level of microcirculation in the kidneys and a decrease in the severity of damage according to the data of a pathomorphological examination at all time points of the experiment. A higher efficiency of correcting ischemic and reperfusion renal injuries was observed when using a combination of the said pharmacological agents. A series of experiments with glibenclamide demonstrated that its preliminary administration levels the renoprotective properties of carbamylated darbepoetin and udenafil. The ability of the studied pharmacological agents to reduce lipopolysaccharide-induced expression of nuclear factor kappa B in mononuclear cells was also demonstrated. The results of the research suggest that the renoprotective effects of carbamylated darbepoetin, udenafil, and their combination are realized through ATP-dependent potassium channels and nuclear factor kappa B. Conclusion: Pharmacological preconditioning with carbamylated darbepoetin and udenafil reduces the severity of acute kidney injury induced by ischemia-reperfusion. Graphical abstract: HTML XML PDF
      PubDate: Thu, 28 Jan 2021 22:50:50 +020
       
 
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