T A Voronina

Russian Academy of Medical Sciences, Moskva, Moscow, Russia

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Publications (407)113.03 Total impact

  • [Show abstract] [Hide abstract]
    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; · 0.34 Impact Factor
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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). · 0.32 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. · 0.34 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.
    Acta naturae. 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. · 0.34 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). · 0.32 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 01/2013; 83(12). · 0.43 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 01/2013; · 0.32 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. · 0.34 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. · 0.34 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). · 0.32 Impact Factor
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    ABSTRACT: The synthesis of compounds effective in the treatment of anxiety—depression disorders is described. It is established that 4,6-dimethyl-2-(4-chlorophenyl)-2,3-dihydro-1H-pyrazolo[4,3-c]pyridine-3-one hydrochloride (IVa) possesses combined antidepressant and anxiolytic properties. Advantages of IVa are low toxicity and the absence of side effects typical of antidepressants (elevated anxiety) and benzodiazepine anxiolytics (myorelaxant and sedative action).
    Pharmaceutical Chemistry Journal 04/2012; 46(1). · 0.32 Impact Factor
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    ABSTRACT: Effects of the novel antiparkinsonian drug himantane and amantadin were studied in rats with intracerebral posttraumatic hematoma. Drugs were administered first at 3.5 hours after surgery and then for 4 consecutive days. Effects were registered on days 1, 3, 7 and 14 after surgery. It was shown that both drugs significantly decreased mortality and improved motor activity, exploratory behavior and memory. Amantadin was more effective in tests for motor activity and exploratory behavior. Himantane 5 mg/kg i.p demonstrated the more pronounced activity in restoring memory. The results obtained testify for neuroprotective properties of the novel antiparkinsonian drug himantane.
    Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova / Ministerstvo zdravookhraneniia i meditsinskoi promyshlennosti Rossiiskoi Federatsii, Vserossiiskoe obshchestvo nevrologov [i] Vserossiiskoe obshchestvo psikhiatrov 01/2012; 112(9):63-66. · 0.06 Impact Factor
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    ABSTRACT: We studied changes in the levels of inhibitory and excitatory neurotransmitters in female rat brain structures during different phases of the estrous cycle in health and after creation of a cobalt epileptogenic focus at stage I of epileptogenic system development. The most pronounced shifts were found in the contralateral cortex, where the levels of GABA and glycine decreased significantly during the diestrus-2 phase (corresponding to menstruation), which attests to a convulsive threshold decrease during this period.
    Bulletin of Experimental Biology and Medicine 11/2011; 152(1):47-9. · 0.34 Impact Factor
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    ABSTRACT: We compared two modifications of Vogel conflict test and assessed anxyolitic activity of two drugs: diazepam (benzodiazepine anxiolitic) and tenoten (ultra-low doses of antibodies to S-100 protein) in both modifications of the test. It was found that the intensity of anxiolitic effect of the drugs depends on the conditions of Vogel test.
    Bulletin of Experimental Biology and Medicine 07/2011; 151(3):336-9. · 0.34 Impact Factor
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    ABSTRACT: Chronic administration of levodopa and benserazide (10 and 15 mg/kg, respectively) cause the development of dyskinesia in rats with model parkinsonian syndrome induced by injection of 6-hydroxydopamine in left substantia nigra. The chronic administration of these drugs together with amantadine (20 mg/kg) accelerates the onset of latency and increases the magnitude of dyskinesia. Chronic administration of levodopa and benserazide together with hemantane (10 mg/kg) slows down the development and decreases the magnitude of levodopa-induced abnormal involuntary movements as measured for limb, orolingual and rotatory movements.
    Eksperimental'naia i klinicheskaia farmakologiia 01/2011; 74(7):9-12.
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    ABSTRACT: We studied the effects of administration of the new nootropic drug phenotropil (N-carbamoylmethyl-4-phenyl-2-pyrrolidone) at a dose of 100 mg/kg on the quantitative characteristics of dopamine (DA), serotonin (5-HT), glutamate (NMDA), GABA-A (BDZ), and acetylcholine (nACh) receptors in rats using the conditioned passive avoidance task (PAT) under normal conditions and during scopolamine-induced amnesia ex vivo. We found that the cholinolytic drug scopolamine induced a substantial increase in the density (B max) of n-choline receptors in the cortex (by 99% as compared to the control) and NMDA receptors in the hippocampus (by 93%). A single administration of phenotropil (100mg/kg, intraperitoneally) abolished the effect of scopolamine and decreased the number of nACh and NMDA receptors by 46% and 14%, respectively. Phenotropil also abolished the effect of scopolamine on the benzodiazepine receptors and dopamine D1 receptors. Scopolamine decreased the density of D1 receptors by 20% and BDZ receptors by 17%, whereas phenotropil increased the density of receptors by 16% and 25%, respectively. Phenotropil considerably increased the density of dopamine D2 and D3 receptors by 29% and 62%, respectively. Scopolamine also increased the density of D3 receptors by 44% as compared to the control. We did not find any changes in the binding characteristics of 5-HT2 receptors during scopolamine-induced amnesia or during phenotropil treatment. These results demonstrate the role of these receptors in the development of scopolamine-induced amnesia and in neurochemical mechanisms of the anti-amnestic effects of phenotropil. Keywordsphenotropil–nootropic drugs–scopolamine–PAT–dopamine–serotonin–acetylcholine–glutamate–benzodiazepines–striatum–frontral cortex–hippocampus
    Neurochemical Journal 01/2011; 5(2):115-125. · 0.24 Impact Factor
  • ESNP, St. Peterburg,; 01/2011
  • European Neuropsychopharmacology - EUR NEUROPSYCHOPHARMACOL. 01/2011; 21.

Publication Stats

310 Citations
113.03 Total Impact Points

Institutions

  • 1980–2014
    • Russian Academy of Medical Sciences
      • Institute of Pharmacology
      Moskva, Moscow, Russia
  • 2013
    • Federal State Budgetary Institution "Scientific Centre of Children Health" under the Russian Academy of Medical Sciences
      Moskva, Moscow, Russia
  • 1996–2013
    • Russian Academy of Sciences
      • Institute of Pharmacology
      Moskva, Moscow, Russia
  • 2003–2011
    • Materia Medica Holding
      Moskva, Moscow, Russia
  • 2005
    • Aristotle University of Thessaloniki
      • Department of Pharmaceutical Chemistry
      Thessaloníki, Kentriki Makedonia, Greece
  • 2004
    • Moscow State Textile University
      Moskva, Moscow, Russia
  • 1998
    • Lomonosov Moscow State University
      Moskva, Moscow, Russia
  • 1996–1997
    • Research Institute of Cytochemistry and Molecular Pharmacology
      Moskva, Moscow, Russia
  • 1994–1997
    • National Academy of Sciences of Ukraine
      • A. V. Bogatsky Physico-Chemical Institute
      Kievo, Kyiv City, Ukraine
    • University of Helsinki
      • Division of Pharmacology and Toxicology
      Helsinki, Province of Southern Finland, Finland
  • 1977
    • Institute of General and Inorganic Chemistry
      Kievo, Kyiv City, Ukraine