Vol 12, No 2 (2014)


Structure, functions of p-glycoprotein and its role in rational pharmacotherapy

Yakusheva E.N., Shulkin A.V., Popova N.M., Chernyh I.V., Titov D.S.


In the review of literature, the structure and functions of P-glycoprotein are characterized, features of its substrates, inductors and inhibitors and possibility of forecasting of belonging to them new medicinal substances are described, molecular mechanisms of activity changes of the transporter under the influence of various factors are presented.
Reviews on Clinical Pharmacology and Drug Therapy. 2014;12(2):3-11
pages 3-11 views

Pharmacology of trekrezan, a new immune modulator and adaptogenic

Shabanov P.D., Zarubina I.V., Mokrenko E.V.


The analysis of literatural and proper experimental data on toxicology and pharmacology of trekrezan, a new synthetic immune modulator and adaptogenic, is reviewed. The data on acute and chronic toxicity as well as phamacodynamic effects of trekrezan and molecular mechanisms of its action are observed. The main attention is paid to study adaptogenic, immune stimulating and anti-inflammatory properties of trekrezan (effect on cell and humoral immunity, phagocytosis, interferonogenesis). The special part describes the influence of trekrezan and combination on its basis (with polyoxidonium, metaprot) on structural, metabolic and immunological changes in the lung and blood lymphocytes of rats in acune bronchopulmonary inflammation, experimental prostatitis and gingivitis. In conclusion, a schedule illustrating connections between pharmacodynamic effects and systemic and molecular mechanisms is analysed.
Reviews on Clinical Pharmacology and Drug Therapy. 2014;12(2):12-27
pages 12-27 views

Mitochondrial targets for pharmacological regulation of cell adaptation to hypoxia

Novikov V.E., Levchenkova O.S.


The review is devoted to the role of a number of mitochondrial factors in the regulation of cell adaptation to hypoxia and ischemia. The mechanisms of cell adaptation involving factors such as the mitochondrial ATP-dependent potassium channel, mitochondrial megapora, mitochondrial nitric oxide synthase, reactive oxygen species are discussed in the paper. The possibility of pharmacological regulation of cell adaptation with help of target action on mitochondrial components is proposed. This approach is a promising direction for drug discovery for correction of diseases with hypoxia and ischemia in their pathogenesis.
Reviews on Clinical Pharmacology and Drug Therapy. 2014;12(2):28-35
pages 28-35 views

Characteristics of external respiration of rats in acute hypercapnic hypoxia and its correction by new metal-complex antihypoxant

Sosin D.V., Yevseyev A.V., Pravdivtsev V.A., Shabanov P.D.


Changes of external respiration parameters have been studied in experimental rats after oral introduction of new selenium-containing metal-complex substance πQ1983 in dose 100 mg/kg before and under action of acute hypercapnic hypoxia (AH+Hc). A substance for comparison was metabolic antihypoxant amthizole administered in similar way and dosage. The substances were introduced 90 min before (incubation period) placement of animals into hypoxic chambers with 1.0 L free volume. During each experiment as well as during AH+Hc a respiration curve called pneumobarogramm (PBG) was recorded continually. It has been established that the substance πQ1983 decreases parameters of lungs ventilation in the rats. According to PBG dynamics, rats protected by the substance demonstrated a high resistance level to the aroused acute hypoxia with hypercapnia, that expressed by weakening of early reactions from respiratory system under hypercapnia action, twice longer life span of animals in hypoxic experiment, and by rising of possibility to withstand low oxygen concentration. It has been proved that the substance πQ1983 significantly surpass a substance for comparison amthizole in both antihypoxic activity and influence on external respiration parameters.
Reviews on Clinical Pharmacology and Drug Therapy. 2014;12(2):36-42
pages 36-42 views

Antioxidant activity of catecholamines as a chane of them antistress effect

Shilov G.N., Ivanyutin V.A.


The antioxidant activity of some native catecholamines (adrenaline, noradrenaline, dopamine), water-soluble antioxidant emoxipine, agonist (apomorphine) and antagonist (haloperidol) of dopamine receptors was assessed as their influence on malonic dialdehyde content and products of lipid peroxidation in homogenates and suspension of the rat cortical brain cells. All catecholamines (adrenaline, noradrenaline, dopamine in concentrations of 10-4 M and 10-5 M) possessed a high (compartable with emoxipine) antioxidant activity. The most antioxidant effect was registered in apomorphine. The inhibitory action of apomorphine on lipid peroxidation in the brain cortex can be a result from both dopamine receptor activation and “direct” antioxidant mechanism.
Reviews on Clinical Pharmacology and Drug Therapy. 2014;12(2):43-46
pages 43-46 views

The influence of experimentally changed thyroid status on cognitive activity and angiogenesis in brain of female of inbred mice С3 Н-А

Glushakov R.I., Kozyrko E.V., Raskin G.A., Karpova I.V., Lebedev A.A., Mikheev V.V., Tapilskaya N.I., Proshin S.N.


The study was performed using 33 virgin females of inbred mice C3H-A. The animals were randomized as follows 3:2:2. The first group was hyperthyroid (n1=15), the second hypothyroid (n2=10) and the third euthyroid (control) (n3=8). The results of individual behavior investigation as to 18 and 40 weeks of our experiment in “open field” test clarified that quantitative traces of almost whole components of cognitive activity was much higher in hyperthyroid mice as compared to other groups (control and hypothyroid ones). The cognitive behavior activity has gradually been decreasing in hypothyroid group especially in connection to burrow reflex. As to those elements of behavior which are of characteristics of emotions the results were a bit different. The emotional characteristics were more expressed in hyperthyroid group as compared to control and hypothyroid ones. The immunohistochemical investigations clearly showed that expression of vascular endothelial growth factor (VEGF) in neocortex and hyppocampus prevails in hyperthyroid mice and less expressed in animals deprived of thyroid hormones (p < 0.05). The level of glial fibrillar acidic protein (GFAP) expression was significantly lower in brain of hypothyroid animals (p < 0.05). Otherwise the level of platelet derived growth factor receptor-α (PDGF-Rα) expression was much higher in brain of hypothyroid mice (p < 0.05). Our results presented for this paper confirmed the key role of thyroid hormones in regulation of cell interaction not only for developing neural cells but also for adult central nerve system.
Reviews on Clinical Pharmacology and Drug Therapy. 2014;12(2):47-53
pages 47-53 views

Perspectives of D1 dopamine antagonists using in treatment of nervous and psychic disorders with (+)-SCH-23390 as an example

Bukinich A.A.


The effect of dopamine (DA), its agonists and antagonists on the amplitude of GABA-activated currents of isolated multipolar spinal cord neurons (both motoneurons and interneurons) of larva of the lamprey Lampetra planeri by means of patch-clamp method in the whole cell configuration was studied. (+)-SCH-23390, a D1-DA receptors antagonist was shown to block dopamine effects on GABA-activated currents by 63.0 ± 4.7 % and by 77.1 ± 2.0 %. Effects of (-)quinpirol, a D2-DA receptors agonist, on GABA-activated currents were blocked by means of (+)-SCH-23390 by 78.8 ± 0.4 % and by 85.0 ± 5.7 %. Because of chemoactivated currents are in full accordance with a gradual scale, the results on blocking D1-DA receptors by (+)-SCH-23390 are ideal ones and that is the possible basis to further clinical aprobation of (+)-SCH-23390 for treatment of epilepsy, neurotic reactions and depression.
Reviews on Clinical Pharmacology and Drug Therapy. 2014;12(2):54-58
pages 54-58 views

Experimental investigation of the lipin gravidoprotective action in the model of placental disfunction caused by oxidative stress

Kudina O.V.


In the model of placental insufficiency caused by tetrachlormethane during organogenesis in rats, a pronounced effect of the gravidoprotective drug lipin was found assessed in their ability to prevent intrauterine growth retardation of rats and to normalize the morphological changes in the liver, kidney and placenta of pregnant rats. The drug lipin exceeds the reference drug essentiale on the sum of these indicators.
Reviews on Clinical Pharmacology and Drug Therapy. 2014;12(2):59-64
pages 59-64 views

Analysis of neuroprotective effects of polyprenols in a rat model of posttraumatic stress disorder

Bakunina N.S., Lebedev A.A., Tsikunov S.G., Soultanov V.S., Shabanov P.D.


The purpose of investigation was to assess protective action of polyprenols (2 and 10 mg/kg) in a rat model of posttraumatic stress disorder (PTSD). PTSD was reproduced in situation of unavoidable vital stress in rats by replacing them into a cell with hungry piton. For the five first minutes the piton was separated from the rats with transparent wall to get acquainted each other with a situation. Then, the wall was elevated, and piton seized a rat, asphyxied it when other rats (22) observed at the situation. The majority of rats were collected in the corner dying away from the beast. The other rats behaved themselves differently. Some of them attacked the piton, bited it, but the majority raced chaotically on the cell with piton. The exposure of rats with piton was 20 minutes. For that time it seized and asphyxied 1 or 2 rats. Polyprenols (from 8 till 18 isoprene units) were injected i. p. in doses of 2 or 10 mg/kg in oil solution for 7 days beginning with 1st day of the experiment (the first injection was 1 h after psychogenic exposure). The behavioral reactions were assessed in open field, elevated plus maze, in Porsolt’s test and in one trial passive avoidance response. The effects of polyprenols of 2 and 10 mg/kg were different. Polyprenols 2 mg/kg did not change horizontal and vertical motor activity in rats, moderately (in 1.5-fold) decreasing explorative activity and increasing grooming in open field. Emotional reactions were not changed. In the elevated plus maze, polyprenols 2 mg/kg possessed mild anxiolytic activity performed in 2.5-fold elevation of hangings number. In Porsolt’s test on depression, polyprenols 2 mg/kg moderately increased time of active swimming and sharply decreased time of immobilization (up to zero). That indicated on antidepressant properties of this dose (2 mg/kg) of polyprenols. In passive avoidance test, psychogenic stress facilitated formation and storage of habit (only 10 % of rats entered the dark chamber in 24 h after formation of the habit compared with 60 % in naïve rats). Polyprenols 10 mg/kg moderately activated explorative behavior without any effect on motor activity. In the elevated plus maze, the effects of polyprenols 2 and 10 mg/kg were similar in general. In Porsolt’s test, polyprenols 10 mg/kg did not perform a significant antidepressant effect. At last, in passive avoidance test, 30 % of rats have not learned after psychogenic stress, and the learned rats reproduced the passive avoidance response with phenomenon of hypermnesia, as in control group. So, polyprenols 2 and 10 mg/kg possess anxiolytic and antidepressant activity in a rat PTSD model. Polyprenols 2 mg/kg are more effective than polyprenols 10 mg/kg.
Reviews on Clinical Pharmacology and Drug Therapy. 2014;12(2):65-70
pages 65-70 views

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