Vol 12, No 2 (2014)

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.

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.

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.

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.

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.