T A Voronina

Russian Academy of Medical Sciences, Moskva, Moscow, Russia

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Publications (422)281.08 Total impact

  • E A Ivanova · I G Kapitsa · E A Val'dman · T A Voronina
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    ABSTRACT: Hemantane demonstrated a pronounced antiparkinsonian activity in the model of hemiparkinsonian syndrome provoked in rats by unilateral intracerebral injection of 6-hydroxydopamine, which was comparable to efficacy of levodopa in decreasing the duration of cataleptogenic state and the degree of akinesia of the contralesional forelimb assessed in the cylinder test. In the stepping test, hemantane exerted a long-term effect in contrast to levodopa, which diminished its beneficial action to the treatment day 21. In the swing test, the behavior normalized only by hemantane.
    Bulletin of Experimental Biology and Medicine 07/2015; DOI:10.1007/s10517-015-2968-8 · 0.37 Impact Factor
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    ABSTRACT: We studied antihypoxic activity of analogs of endogenous cyclic dipeptide cycloprolylglycine in a mouse model of normobaric hypoxia with hypercapnia and found that antixypoxic effect depends on the structure of the substance. It was shown that different pharmacophores are responsible for the antihypoxic, nootropic, and anxiolytic effects of cycloprolylglycine.
    Bulletin of Experimental Biology and Medicine 02/2015; 158(4). DOI:10.1007/s10517-015-2784-1 · 0.37 Impact Factor
  • N V Kudryashov · T S Kalinina · T A Voronina
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    ABSTRACT: The experiments has been designed to study unpredictable chronic mild stress effect on anti-depressive activities of amitriptyline (10 mg/kg) and fluoxetine (20 mg/kg) in forced swim test in male outbred mice. It is shown that acute treatment with fluoxetine does not produce any antidepressant effects in mice following stress of 14 days while the sub-chronic injections of fluoxetine result in more deep depressive-like behavior. In 28 daily stressed mice, antidepressant effect of fluoxetine is observed independently of the injection rates. Amitriptyline demonstrates the antidepressant activity regardless of the duration of stress or administration scheduling, but at the same time the severity of anti-immobilization effect of amitriptyline in stressed mice is weaker in compare to non-stressed trails. Thus, the injection rates and duration of unpredictable mild chronic stress are the parameters that determine the efficiency of antidepressants in the mouse forced swimming test.
    Rossiĭskii fiziologicheskiĭ zhurnal imeni I.M. Sechenova / Rossiĭskaia akademiia nauk 02/2015; 101(2):163-70.
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    ABSTRACT: We studied behavioral and neurochemical alterations that were induced by modeling of Alzheimer’s disease (AD) using bilateral intracerebroventricular administration of Aβ25-35 at a dose of 7.5 nmol in each ventricle. After 5.5 weeks, cognitive and psychoemotional alterations in the Morris spatial learning and Porsolt’s forced-swim tests were observed in rats with strong symptoms that are typical of AD. Measurement of the contents of monoamines and their metabolites in rat-brain structures was performed using the HPLC with the ECD method 1 day after the end of the tests. In the dorsal striatum, we found a decrease in the contents of metabolites of dopamine (DA), including homovanillic acid (HVA), 3,4-dihydroxyphenylacetic acid (DOPAC), and 3-methyltyramine (3-MT), and a decrease in the indices of DA utilization, including DOPAC/DA and HVA/DA, whereas the DA content was stable in this structure. In the nucleus accumbens (NA, ventral striatum), we found a decreased level of the HVA/DA ratio, which reflects the lower turnover of extracellular DA. We also found a lower turnover of serotonin (5-HT), which was seen as a decrease in the 5-hydroxyindolacetic acid (5-HIAA)/5-HT ratio, whereas the 5-HT content was elevated. In the hypothalamus, we revealed a significant decrease in the DA level and the levels of its metabolites, including 3-MT and HVA, and 5-HT turnover. We found that Aβ25-35 influenced the indices of amino-acidergic neurotransmission, which was reflected by the higher glutamate content in the striatum. Our data show that cerebral neurotransmitter systems, such as the tuberoinfundibular, mesolimbic, and nigrostrial dopaminergic and the striatal serotonergic and glutamatergic systems, are involved in pathophysiological mechanisms of the development of cognitive and psychoemotional impairments that occur in AD, as modeled by administration of Aβ25-35.
    Neurochemical Journal 01/2015; 9(1):39-46. DOI:10.1134/S1819712415010055 · 0.19 Impact Factor
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    ABSTRACT: Anticonvulsant activity and pharmacokinetics of nanoemulsion and unmodified substance of carbamazepine were compared in experiments on mice. Carbamazepine nanoemulsion demonstrated significant anticonvulsant activity and was superior to unmodified substance of carbamazepine against seizures induced by maximum electric shock and picrotoxin. Relative bioavailability of carbamazepine after administration of nanoemulsion was 160% compared to unmodified substance. Carbamazepine nanoemulsion more effectively penetrated through BBB by 1.5 times in comparison with unmodified substance.
    Bulletin of Experimental Biology and Medicine 10/2014; 157(6):742-6. DOI:10.1007/s10517-014-2657-z · 0.37 Impact Factor
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    ABSTRACT: Experiments on adult Wistar rats with streptozotocin-induced diabetes showed that antihyperglycemic activity of an original nootropic and neuroprotective drug Noopept (N-phenylacetyl-L-prolylglycine ethyl ester) is more pronounced under conditions of oral application than after intraperitoneal injection. These data provided a basis for studying the effect of Noopept on major indexes of the incretin system. Streptozotocin was shown to decrease the concentrations of incretin GLP-1 and insulin in the blood. Noopept had a normalizing effect on these parameters. This influence of Noopept was not related to the inhibition of a major enzyme metabolizing incretins (dipeptidyl peptidase IV). A reference drug sitagliptin also increased the contents of incretins and insulin, which was associated with the inhibition of dipeptidyl peptidase IV. It is known that GLP-1 increases NGF expression in the insular system. Our results suggest that the increase in incretin activity contributes to the antiapoptotic effect of Noopept on pancreatic β cells. The mechanism for an increase in blood GLP-1 level after oral application of Noopept requires further investigations.
    Bulletin of Experimental Biology and Medicine 07/2014; 157(3). DOI:10.1007/s10517-014-2562-5 · 0.37 Impact Factor
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    ABSTRACT: Developing diabetes was modeled on adult male Wistar rats by repeated intraperitoneal injections of streptozotocin in a subdiabetogenic dose of 30 mg/kg for 3 days. Proline-containing dipeptide drug Noopept or a standard diabetic drug dipeptidyl peptidase-4 inhibitor sitagliptin was administered per os in a dose of 5 mg/kg before each injection of the toxin and then for 16 days after streptozotocin course. In active control group, spontaneously increase glucose level and reduced tolerance to glucose load (1000 mg/kg intraperitoneally) were observed on the next day after the third administration of toxin. Basal glucose level decreased by day 16, but glucose tolerance remained impaired. Noopept normalized the basal blood glucose level and tolerance to glucose load on the next day after administration of streptozotocin. The effect of Noopept persisted to the end of the experiment. At early terms of the experiment, sitagliptin was somewhat superior to Noopept by the effect on baseline glucose level, but was inferior by the influence on glucose tolerance.. By the end of the experiment, Noopept significantly (by 2 times) surpassed sitagliptin by its effect on glucose tolerance.
    Bulletin of Experimental Biology and Medicine 01/2014; 156(3):342-6. DOI:10.1007/s10517-014-2345-z · 0.37 Impact Factor
  • T A Voronina · V B Larionov · N Ia Golovenko · L N Nerobkova
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    ABSTRACT: The pharmacodynamics and pharmacokinetics of hemisuccinate 3-hydroxyphenazepam (HS-3-HPh, levana)--a new hypnotic 1,4-benzodiazepine derivative--have been studied. It is established that HS-3-HPh in doses of 0.05, 0.1 and 2 mg/kg produces reliable hypnotic action (shortens the period of falling asleep, reduces the number of awakenings at night-time, and increases sleep duration) in the hexenal sleep potentiation test on mice. After a 7-day drug administration, no withdrawal syndrome has been observed. The concentration of 3-oxyphenazepam (3-OP, the main metabolite of HS-3-HPh) in brain after drug administration is significantly higher than the content of 3-OP upon its introduction. The content of 3-OP upon its introduction rapidly decreases, while that upon the administration of HS-3-HPh is retained on a stationary level for a rather long time (about 6 h). It can be suggested that a specific character of HS-3-HPh hypnotic action is determined by peculiarities of its pharmacokinetics, namely, easier entering the brain and subsequent hydrolysis with release of the active metabolite (3-OP).
    Eksperimental'naia i klinicheskaia farmakologiia 01/2014; 77(1):3-6.
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    ABSTRACT: Hemantane is a novel antiparkinsonian drug that is undergoing clinical trials. Hemantane in the dosage range 10 – 40 mg/kg demonstrated anti-inflammatory activity and decreased statistically significantly the intensity of the exudative reaction in an acetic-acid peritonitis model in mice. Hemantane (10 mg/kg) in a neuro-inflammation model induced by lipopolysaccharide injection in rats prevented loss of body mass, development of forepaw akinesia contralateral to the operation, and smell disturbance.
    Pharmaceutical Chemistry Journal 01/2014; 47(10). DOI:10.1007/s11094-014-0994-x · 0.30 Impact Factor
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    ABSTRACT: The research on the nansomal forms s of low-sialylated recombinant human erythropoietin (ls-rhEPO) gave evidence for the efficiency of the nanotechnological approach to targeted delivery of this protein to the brain of experimental animals. Nanosomal ls-rhEPO formulations were found to exhibit neuroprotector activity. The established ability of the nanosomal formulations of ls-rhEPO to enhance BDNF and NGF gene expression in animal brain is to a great extent responsible for the mechanism of the neuroprotector action of this protein.
    Russian Journal of General Chemistry 12/2013; 83(12). DOI:10.1134/S1070363213120566 · 0.42 Impact Factor
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    ABSTRACT: A series of new 1,2,4,5-tetrahydro-3H-pyrrolo[1,2-a][1,4]diazepin-3-one derivatives were synthesized from widely available furfurol, 3-aminopropionic acid, and amines. The antidepressant and anxiolytic properties of the obtained compounds were investigated. Results of Nomura and Porsolt forced swimming tests showed that some of the compounds exhibited antidepressant activity at doses of 7 μmol/kg (1.1 – 2.2 mg/kg). Use of the Vogel conflict test showed that several compounds possessed anxiolytic activity at the same doses. The activities of the most active compounds exceeded those of the reference drugs, antidepressant amitriptyline and daily tranquilizer medazepam, at doses of 10 mg/kg.
    Pharmaceutical Chemistry Journal 12/2013; 47(9). DOI:10.1007/s11094-013-0981-7 · 0.30 Impact Factor
  • Alexander Shimshirt · Tatiana Kalinina · Tatiana Voronina
    Behavioural Pharmacology 10/2013; 24:e41. DOI:10.1097/01.fbp.0000434820.95688.45 · 2.19 Impact Factor
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    ABSTRACT: A large amount of clinical and experimental data suggest the involvement of neurotrophins, in particular the brain-derived neurotrophic factor (BDNF), in depression pathogenesis. However, the therapeutic use of BDNF is limited because of its instability in biological fluids, poor blood-brain barrier (BBB) permeability, and the presence of side effects. A low-molecular-weight mimetic GSB-106, which is a substituted dimeric dipeptide bis(N-monosuccinyl-L-seryl-L-lysine)hexamethylenediamide, was designed and synthesized based on the BDNF fourth loop structure at the V.V. Zakusov Institute of Pharmacology (RAMS). GSB-106 was found to exhibit an antidepressant activity in various models of depressive-like state when administered intraperitoneally to outbred mice and rats. An effect for the substance, when administered daily for 4-5 days, was detected in the Porsolt forced swimming test (0.1 and 1.0 mg/kg) and in the tail suspension test in mice (1.0 and 1.5 mg/ kg). An effect for GSB-106 at doses of 0.1 and 0.5 mg/kg was observed after a single application in experiments on rats in the Nomura water wheel test. The obtained evidence supports the hypothesis on the involvement of BDNF in the pathogenesis of various depression conditions, thus opening prospects for searching for new original antidepressants.
    10/2013; 5(4):105-9.
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    ABSTRACT: Human recombinant erythropoietin adsorbed on poly(butyl)cyanoacrylate nanoparticles and administered intraperitoneally in a dose of 0.05 mg/kg exhibited a neuroprotective effect in experimental intracerebral posttraumatic hematomas (hemorrhagic stroke) and reduced animal mortality. Human recombinant erythropoietin, native and adsorbed on lactic and glycolic acid copolymer-based nanoparticles, exhibited no antistroke effect on this model. Analysis of reverse transcription PCR products showed that human recombinant erythropoietin adsorbed on poly(butyl)cyanoacrylate nanoparticles more than 2-fold increased the expression of BDNF and NGF neurotrophins in the rat brain frontal cortex and hippocampus.
    Bulletin of Experimental Biology and Medicine 05/2013; 155(2):242-244. DOI:10.1007/s10517-013-2123-3 · 0.37 Impact Factor
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    ABSTRACT: The aim of the present work was to develop methods for the preparation of a nanosomal form of low-sialylated recombinant human erythropoietin (ls-rhEPO), which has neurotropic antihemorrhagic activity. Measurements were made of the sorption of erythropoietin to nanoparticles made of lactic acid homopolymer or lactic acid/glycolic acid copolymer, mean nanoparticle size, and the resistance of the resulting complex to aggregation. The most effective sorption (greater than 80%) was achieved using a copolymer with equal proportions of lactic and glycolic acids (50:50). Experiments using an intracerebral post-traumatic hematoma model in rats demonstrated that nanosomal ls-rhEPO had neuroprotective actions, based on its ability to decrease death in the experimental animals (77.8% survived, which was 40% more than in the control group). Nanosomal ls-rhEPO was found to have no effect on hematopoiesis in conditions of chronic administration.
    Pharmaceutical Chemistry Journal 01/2013; 46(10). DOI:10.1007/s11094-013-0858-9 · 0.30 Impact Factor
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    ABSTRACT: We studied the effects of new nootropic and neuroprotective drug Noopept (N-phenylacetyl-L-prolylglycine ethyl ester) in various dosage regimens on the dynamics of glycemia, body weight, and pain sensitivity in rats receiving diabetogenic toxin streptozotocin. In experimental diabetic rats, Noopept alleviated glycemia and weight loss and normalized enhanced pain sensitivity. The normalizing effect of Noopept was most pronounced when it was administered as a preventive agent prior to injection of the toxin. Both preventive and therapeutic administration of Noopept (delayed injections included) significantly weakened the examined metabolic effects of diabetogenic toxin. Possible mechanisms of the antidiabetic action of Noopept are analyzed.
    Bulletin of Experimental Biology and Medicine 12/2012; 154(3):334-338. DOI:10.1007/s10517-013-1944-4 · 0.37 Impact Factor
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    ABSTRACT: A concept of physicochemical forms of biologically active substances introduced in investigation of the action mechanism of ultra-low doses allows qualitative explanation of the main effects of ultra-low doses, chemical diversity of biologically active substances, and physical boundaries for these effects. Phenazepam was shown to possess activity in ultra-low doses only in disperse state, in the form of nanoparticles with a diameter <100-300 nm; these nanoparticles appear as micelles of surface active substances and solvated. Panavir possesses pharmacological activity in ultra-low doses and appears as nanoparticles with a diameter of 200-300 nm, which have uncompensated negative surface charge and polymer nature.
    Bulletin of Experimental Biology and Medicine 08/2012; 153(4):455-8. DOI:10.1007/s10517-012-1739-z · 0.37 Impact Factor
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    ABSTRACT: Two new amines were synthesized from 2-aminoadamantane and the available monoterpenoid aldehydes citral and (–)-myrtenal. It was established that the synthesized amines possessed anxiolytic activity.
    Pharmaceutical Chemistry Journal 08/2012; 46(5). DOI:10.1007/s11094-012-0775-3 · 0.30 Impact Factor
  • Vic. V. Yasnetsov · S. Ya. Skachilova · L. N. Sernov · T. A. Voronina · V. V. Yasnetsov
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    ABSTRACT: The new 3-hydroxypyridine derivative 2-ethyl-6-methyl-3-hydroxypyridinium N-acetyl-L-glutamate (EMOP-AG) was synthesized. It was established that EMOP-AG (10 and 30 mg/kg, single administration) exhibited antihypoxic activity on various models of acute hypoxia (baric hypoxia with hypercapnia and hemic and histotoxic hypoxia) in mice and produced an equal or stronger effect than reference drugs (amtizol, mexidol, and emoxipin). EMOP-AG (10 and 30 mg/kg) had a marked neuroprotective effect on rats with bilateral ligation of common carotid arteries and was more effective in the treatment of neurologic deficiency than amtizol (10 and 30 mg/kg/day), mexidol (90 and 120 mg/kg/day), and emoxipin (120 mg/kg/day). It was also established that EMOP-AG (30 mg/kg) could prevent amnesia in a step-down passive avoidance situation caused by different factors (maximal electroshock, scopolamine, acute baric hypoxia with hypercapnia, and the combined action of extreme factors).
    Pharmaceutical Chemistry Journal 07/2012; 46(4). DOI:10.1007/s11094-012-0760-x · 0.30 Impact Factor

Publication Stats

552 Citations
281.08 Total Impact Points


  • 1977–2015
    • Russian Academy of Medical Sciences
      • Institute of Pharmacology
      Moskva, Moscow, Russia
    • Institute of General and Inorganic Chemistry
      Kievo, Kyiv City, Ukraine
  • 1996–2013
    • Russian Academy of Sciences
      • Institute of Pharmacology
      Moskva, Moscow, Russia
  • 2005–2011
    • Russian Medical Society
      Moskva, Moscow, Russia
  • 2003–2011
    • Materia Medica Holding
      Moskva, Moscow, Russia
  • 2009
    • University of Geneva
      • Department of Rehabilitation and Geriatrics
      Genève, Geneva, Switzerland
  • 2008
    • Moscow Medical
      Moskva, Moscow, Russia
  • 1998–2005
    • Lomonosov Moscow State University
      • Faculty of Biology
      Moskva, Moscow, Russia
  • 2004
    • Moscow State Forest University
      Mytishi, Moskovskaya, Russia
  • 1980–1996
    • Research Institute of Cytochemistry and Molecular Pharmacology
      Moskva, Moscow, Russia
  • 1994
    • University of Helsinki
      • Division of Pharmacology and Toxicology
      Helsinki, Uusimaa, Finland
    • National Academy of Sciences of Ukraine
      • A. V. Bogatsky Physico-Chemical Institute
      Kievo, Kyiv City, Ukraine
  • 1988
    • Institute of Physiological Active Compounds
      Charkow, Kharkiv, Ukraine