Zakusov Research Institute of Pharmacology

Moscow, Russia

Zakusov Research Institute of Pharmacology

Moscow, Russia
SEARCH FILTERS
Time filter
Source Type

Zhanataev A.K.,Zakusov Research Institute of Pharmacology | Anisina E.A.,Zakusov Research Institute of Pharmacology | Chayka Z.V.,Zakusov Research Institute of Pharmacology | Miroshkina I.A.,Zakusov Research Institute of Pharmacology | Durnev A.D.,Zakusov Research Institute of Pharmacology
Cell and Tissue Biology | Year: 2017

The phenomenon of atypical DNA comets observed in experiments using DNA-comet assay is described and illustrated. The current hypotheses explaining the nature of atypical DNA comets and our own take on the issue are considered. The practical importance of the registration of atypical DNA comets during the assessment of genotoxicity is discussed. © 2017, Pleiades Publishing, Ltd.


Zhanataev A.K.,Zakusov Research Institute of Pharmacology | Eremina N.V.,Panacela Labs | Chayka Z.V.,Zakusov Research Institute of Pharmacology | Kazey V.I.,Panacela Labs | And 4 more authors.
Mutation Research - Genetic Toxicology and Environmental Mutagenesis | Year: 2017

The class of carbazoles includes compounds with high biological activities and broad spectra of action. PLX01107 and PLX01008 are xenomycins, a new subclass of antimicrobial carbazole derivatives demonstrating strong antifungal activity in vitro. We performed three tests, a bacterial reverse mutation assay (Ames test), in vitro cytokinesis-block micronucleus assay, and chromosome aberration test in mouse bone marrow cells, to investigate the possible genotoxicity of these compounds. Despite their structural similarity, the two compounds had different genotoxicity profiles. PLX01008 showed positive effects in all assays. PLX01107 showed no mutagenicity in the Ames test but demonstrated strong cytogenetic activity in vitro and in vivo. PLX01107 was also tested in the in vivo alkaline comet assay, where a weak but statistically significant increase in DNA damage was seen in liver cells 24 h after treatment. Significantly increased levels of formamidopyrimidine DNA glycosylase (FPG)-sensitive sites were found in bone marrow cells of PLX01107-treated mice (FPG-modified comet assay), suggesting induction of oxidative or alkylation damage to DNA. © 2017 Elsevier B.V.


Kudryashov N.V.,Zakusov Research Institute of Pharmacology | Kalinina T.S.,Zakusov Research Institute of Pharmacology | Voronina T.A.,Zakusov Research Institute of Pharmacology
Neuroscience and Behavioral Physiology | Year: 2016

The effects of unpredictable chronic mild stress on the effects of the tricyclic antidepressant amitriptyline (10 mg/kg) and the selective serotonin reuptake inhibitor fluoxetine (20 mg/kg) in the Porsolt test were studied in male mongrel mice. Single doses of fluoxetine given after 14-day chronic mild stress lacked any antidepressant effect, while subchronic administration for 14 days strengthened depressive-like reactions. After stress for 28 days, the antidepressant effect of fluoxetine was present regardless of the number of doses given. Amitriptyline showed antidepressant activity independently of the duration of stress and the administration regime, though the presence of stress decreased the intensity of the antiimmobility effect. Thus, the number of doses and the duration of unpredictable mild stress are parameters determining the efficacy of antidepressants in the forced swimming test. © 2016, Springer Science+Business Media New York.


Gudasheva T.A.,Zakusov Research Institute of Pharmacology | Tarasiuk A.V.,Zakusov Research Institute of Pharmacology | Sazonova N.M.,Zakusov Research Institute of Pharmacology | Pomogaibo S.V.,Zakusov Research Institute of Pharmacology | And 7 more authors.
Russian Journal of Bioorganic Chemistry | Year: 2017

Previously, we prepared dimeric dipeptide mimetics of the first and the fourth loops of the nerve growth factor (NGF): hexamethylenediamides of bis(N-aminocaproyl-glycyl-L-lysine) (GK-6) and bis(N-monosuccinyl-L-glutamyl-L-lysine) (GK-2). Both mimetics activated TrkA-receptors, but induced different postreceptor signal pathways. GK-2 selectively activated PI3K/AKT, whereas GK-6 activated both PI3K/AKT and MAPK/ERK. Both mimetics exhibited a neuroprotective activity. In this study, we continued the investigation of a contribution of separate loop-like structures in the NGF functions and created and studied dimeric dipeptide mimetics based on a beta-turn of the NGF third loop: hexamethylenediamides of bis(N-gamma-hydroxybutyryl-L-lysyl-L-histidine) (GTS-115) and bis(N-acetyl-L-lysyl-L-histidine) (GTS-113). GTS-115 was shown to exhibit the neuroprotective activity in the concentration range from 10–5 to 10–7 М towards the HT-22 cell culture under the conditions of oxidative stress. The acetyl-containing GTS-113 mimetic proved to be inactive. GTS-115 (1 mg/kg/day intraperitoneally, for 7 days, the administration was started 4 h after the operation) exhibited the neuroprotective properties and decreased the infarction volume by 25% on the model of a stroke that was induced by a transient occlusion of the medial cerebral artery of rats. The action mechanism of GTS-115 was studied by Western-blot analysis and this mimetic in a concentration of 10–6 М was shown to activate the TrkA-receptor and both MAPK/ERK and PI3K/AKT basic postreceptor signal pathways. The inhibitory analysis revealed different contributions of these pathways into the GTS-115 neuroprotective effect. The LY294002 selective inhibitor of PI3K completely blocked the neuroprotective effect of GTS-115 in vitro, whereas the PD98059 specific inhibitor of MEK1 and MEK2 decreased this effect only by 10–15%. GTS-115 peptide stimulated a differentiation of the PC12 cells and caused a hyperalgesia in rats. These facts were in a good agreement with the literature data on the participation of the MAP-kinase pathway in these effects. Thus, the third NGF loop and the neighboring first NGF loop activated the postreceptor pathways in a similar way and exhibited the similar activities. © 2017, Pleiades Publishing, Ltd.


Zolotarev Y.A.,Russian Academy of Sciences | Kovalev G.I.,Zakusov Research Institute of Pharmacology | Kost N.V.,Mental Health Research Center | Voevodina M.E.,Mental Health Research Center | And 8 more authors.
Journal of Psychopharmacology | Year: 2016

This study is focused on a new amide derivative of the peptide HLDF-6 (Thr-Gly-Glu-Asn-His-Arg). This hexapeptide is a fragment of Human Leukaemia Differentiation Factor (HLDF). It displays a broad range of nootropic and neuroprotective activities. We showed, for the first time, that the peptide HLDF-6-amide has high anxiolytic activity. We used 'open field' and 'elevated plus maze' tests to demonstrate anxiolytic effects of HLDF-6-amide (0.1 and 0.3 mg/kg intranasally), which were comparable to those of the reference drug diazepam (0.5 mg/kg). Five daily equipotent doses of HLDF-6-amide selectively mitigated anxiety and increased the density of NMDA receptors in the hippocampus of stress-susceptible BALB/c mice, and had no effect on stress-resilient C57BL/6 mice. The subchronic administration of HLDF-6-amide showed no effect on the density of GABAA and nicotine receptors but was accompanied by a nonselective decrease of the 5-HT2A serotonin receptor density in frontal cortex of both strains. The mechanism of the specific anxiolytic activity of HLDF-6-amide may include its action on the NMDA-glutamatergic receptor system of the hippocampus and on serotonin 5-HT2A-receptors in the prefrontal cortex. The psychotropic activity of HLDF-6-amide is promising for its introduction to medical practice as a highly effective anxiolytic medicine for mental and neurological diseases. © British Association for Psychopharmacology.


Belokopytova K.V.,Moldova Academy of Sciences | Belov O.V.,Joint Institute for Nuclear Research | Kudrin V.S.,Zakusov Research Institute of Pharmacology | Narkevich V.B.,Zakusov Research Institute of Pharmacology | And 3 more authors.
Neurochemical Journal | Year: 2016

We studied the effect of carbon ions (12C) with an energy of 500 MeV/nucleon at a dose of 1 Gy on monoamine metabolism in the brains of rats of different ages. Neurochemical parameters that characterize the distribution of noradrenaline (NA), dopamine (DA), serotonin (5-HT), and its metabolites were evaluated during 2 months on days 30 and 90 after the exposure to radiation. We studied the prefrontal cortex, hypothalamus, hippocampus, and striatum. The results showed changes in the activities of the NA, DA, and 5-HT systems in rats of different age groups after exposure to radiation. The most prominent differences in the exposed and control animals were observed in the prefrontal cortex and hypothalamus, which indicates the important role of these brain regions in long-term effects of exposure to radiation on the central nervous system. A comparison of animals from different age groups showed a decrease in the intensity of the temporal changes in all analyzed structures except the striatum in the exposed rats. Based on these findings, we assumed that the activation of compensatory and repairing mechanisms occurs in the late post-radiation period. At relatively low linear energy transfer of particles (10.6 keV/µm), it may lead to the partial recovery of brain functions that were impaired by radiation. At higher values of the linear energy transfer, the compensatory and recovery processes are activated to a lesser degree and functional impairment increases with time. © 2016, Pleiades Publishing, Ltd.


Belokopytova K.V.,Joint Institute for Nuclear Research | Belov O.V.,Joint Institute for Nuclear Research | Kudrin V.S.,Zakusov Research Institute of Pharmacology | Narkevich V.B.,Zakusov Research Institute of Pharmacology | And 4 more authors.
Neurochemical Journal | Year: 2015

We investigated the levels of monoamines and their metabolites in certain brain structures of rats at 30 and 90 days after exposure to carbon ions (12C) with an energy of 500 MeV/nucleon. The linear energy transfer and radiation dose were 10.6 keV/µm and 1 Gy, respectively. The concentrations of substances were measured in five structures of the brain, including the prefrontal cortex, nucleus accumbens, hypothalamus, hippocampus, and striatum. On day 30 after the exposure, the most pronounced changes in the concentration of monoamines and their metabolites were observed in the nucleus accumbens; the smallest changes were found in the hippocampus and striatum. After 90 days, significant changes were still present in the nucleus accumbens. At the same time, these changes became less evident in other structures. A comparison of our results with the data of similar previous experiments (24 hours after exposure) showed that the most pronounced effect was observed soon after radiation exposure. The induced damage diminished at a later period. Based on the results of our study, we made the hypothesis that the change in the metabolism of monoamines may be compensated if the linear-energy transfer values were relatively low (10.6 keV/μm). At higher values of linear-energy transfer, compensatory and regenerative processes did not occur; the effect increased with time. An increased susceptibility of the nucleus accumbens was found at all the time points after the exposure, which may indicate an important role of this brain structure in the radiation-induced impairment of cognitive functions and emotional and motivational states. © 2015, Pleiades Publishing, Ltd.


Pligina K.L.,Zakusov Research Institute of Pharmacology | Zhanataev A.K.,Zakusov Research Institute of Pharmacology | Kulakova A.V.,Zakusov Research Institute of Pharmacology | Chaika Z.V.,Zakusov Research Institute of Pharmacology | Durnev A.D.,Zakusov Research Institute of Pharmacology
Russian Journal of Genetics | Year: 2016

The influence of N-acetylcysteine (ACC) on the cytogenetic effects of etoposide in F1 CBA × C57BL/6 mice was studied. Etoposide introduced intraperitoneally in doses of 10, 20, 40, and 60 mg/kg has a dose-dependent clastogenic activity and has an aneugenic effect with the induction of mainly hypohaploid oocytes. ACC significantly decreases the aneugenic and clastogenic activity of etoposide (20 mg/kg) in oocytes of 6-, 9-, and 12-week-old mice during triple introduction at a dose 200 mg/kg per os. The most pronounced anticlastogenic ACC activity (an 80% decrease) was registered in 9-week-old females; a 100% decrease in aneugenesis was detected in 6-week-old female mice. © 2016, Pleiades Publishing, Inc.


Gudasheva T.A.,Zakusov Research Institute of Pharmacology | Deeva O.A.,Zakusov Research Institute of Pharmacology | Mokrov G.V.,Zakusov Research Institute of Pharmacology | Yarkov S.A.,Zakusov Research Institute of Pharmacology | And 2 more authors.
Doklady Biochemistry and Biophysics | Year: 2015

On the basis of the structure of Alpidem, a pyrazolopyrimidine ligand of the translocator protein (TSPO), a dipeptide TSPO ligand, N-carbobenzoxy-L-tryptophanyl-L-isoleucine amide (GD-23), was designed and synthesized using our own original peptide design strategy. This compound exhibited anxiolytic activity in BALB/cAnN mice in the “open-field” test and in outbred CD1 mice in the “elevated plus maze” test. The stereoselectivity of the anxiolytic effect of GD-23 is demonstrated. The results of this study suggest that GD-23 is a ligand of the translocator protein, and its structure can become the basis for creating anxiolytics with a fundamentally new mechanism of action. © 2015, Pleiades Publishing, Ltd.


PubMed | Zakusov Research Institute of Pharmacology
Type: | Journal: Doklady. Biochemistry and biophysics | Year: 2015

On the basis of the structure of Alpidem, a pyrazolopyrimidine ligand of the translocator protein (TSPO), a dipeptide TSPO ligand, N-carbobenzoxy-L-tryptophanyl-L-isoleucine amide (GD-23), was designed and synthesized using our own original peptide design strategy. This compound exhibited anxiolytic activity in BALB/cAnN mice in the open-field test and in outbred CD1 mice in the elevated plus maze test. The stereoselectivity of the anxiolytic effect of GD-23 is demonstrated. The results of this study suggest that GD-23 is a ligand of the translocator protein, and its structure can become the basis for creating anxiolytics with a fundamentally new mechanism of action.

Loading Zakusov Research Institute of Pharmacology collaborators
Loading Zakusov Research Institute of Pharmacology collaborators