Purpose of the study. Assess anticonvulsant and neuroprotective effects of Cerebrolysin in rats. Material and methods. The study was carried out on 30 white male rats, who received a course of Cerebrolysin. The model of primary-generalized convulsions was reproduced by a single administration of thiosemicarbazide. Results and conclusion. Preliminary introduction of Cerebrolysin reduces the severity and duration of seizures caused by thiosemicarbazide, increases the survival rate of animals. The test drug has a neuroprotective effect on the cells of the cerebral cortex under conditions of ischemia.

The effect of magnesium orotate on the model of primary generalized convulsions in the experiment was studied. The course of administration of magnesium orotate (preparation Magneter) at a dose of 0,06 g / kg of weight reduces the severity and duration of seizures caused by thiosemicarbazide, increases the survival of animals, has a neuroprotective effect, affecting various morphological structures. The drug Magnerot - the donor of magnesium, replenishing in the body the deficit caused by the convulsant.

Effects of tropoxine on activity of isoforms CYP2С9 and CYP2С9 of cytochrome P450 using marker drugs losartane and caffeine were studied. Tropoxine in the effective dose (30 mg/kg) after 4-days intraperitoneal administration (3 times per day) in rats did not produce changes of CYP2C9 and CYP1A2 isoforms actitvity. Study of duration of tropoxine administration on the CYP2C9 acivity changing was shown that 3 and 4 days administration of the drug did not affect neither inhibiting nor inducing effect of CYP2C9 isoform.

Concentration time curves for whole blood and tissue homogenates of 11 different bio-substrates (brain, frontal lobe, heart, aorta, lungs, liver, kidneys, spleen, adrenal capsules, femur, urine) were obtained for lithium citrate at a dose of 1 000 mg/kg. In the course of a non-compartmental analysis of the concentrations dynamics in the whole blood the following values of the pharmacokinetic parameters of lithium citrate were obtained: C_max = 54,1 mcg/l, T_max = 1,50 h, C_last = 33,7 mcg/l, AUC_t = 1776 mcg/l х h, MRT_t = 22,7 h, Lz = 0,004 1/h, T_1/2 = 146 h, CL = 0,014 l/h, V_d = 3,0. Lithium concentrations in the whole blood and in the brain frontal lobe were stable for at least 40...50 hours after overcoming the peak concentration. Multi-compartmental pharmacokinetic analysis showed that the stabilization of the lithium levels in the blood and in the brain is maintained due to the special lithium “depot” that includes brain, aorta, kidneys and femur.

Proteomic analysis indicated 6 target proteins of thioctic acid (TA) and 11 proteins of TA metabolism, all of which are mitochondrial proteins. In the structure of the target proteins (namely, P-protein, H-protein, lipoamide acyltransferase, dihydrolipoyline acetyltransferase, X-protein pyruvate dehydrogenase, dihydrolyloylizine succinyltransferase), TA is a cofactor which is covalently bound to specific lysine residues and which is required for processing glycine and other amino acids, thus maintaining the activity of the Krebs cycle. Insufficient activity of these target proteins (due to either genetic defects or nutritional TA deficiency) leads to mitochondrial insufficiency, hyperglycinemia, biliary cirrhosis, "maple syrup urine" syndrome and other metabolic disorders. Insufficient activity of the 11 proteins of TA metabolism is associated with multiple disorders of mitochondrial function, lactic acidosis and anemia. Thus, TA is fundamentally important for supporting the function of mitochondria and of the cellular energy metabolism.

Dimeric dipeptide mimetic 1st loop of NGF GK-6 (10^-6M) activating as phosphatidylinozitol 3-kinase/Akt and mitogen-activated protein kinase MEK/MAPK/ERK) signaling cascades causes PC12 cell differentiation into neuron-like cells. At the same time dimeric dipeptide mimetic the 4th loop of NGF GK-2 (10^-6M), which activates only phosphatidylinozitol 3-kinase/Akt, does not possess the differentiating effect.

The effects of a new racetam derivative with anticonvulsant activity GIZh-290 (2-oxo-4-phenylpyrrolidin-1-yl) acetic acid and levetiracetam for the content of neuroactive amino acids aspartate, glutamate, taurine, glycine and GABA in homogenates of the hippocampus and prefrontal cortex (PFC) of rat brain using the HPLC method with fluorescent detection were studied. In the hippocampi of intact rats HIZh-290 (5 mg/kg, ip) increased the levels of glutamate, glycine and GABA by 22, 42 and 28 %, and levetiracetam (600 mg/kg), on the contrary, reduced them by 18, 26 and 26 %. At the maximum of lithium-pilocarpine seizures, a decrease in the content of aspartate (-19 %) and an increase in glycine in the PFC (+24 %) were detected. Preliminary administration of GIZh-290 and levetiracetam did not affect these parameters, but caused an increase in taurine concentrations in the PFC homogenates. Thus, the indicators studied are not markers of anticonvulsant action of levetiracetam and GIZH-290, but indicate differences in the mechanisms of the drugs anticonvulsant effect formation.

Using the multiparameter method of EEG analysis with a complex study of coherent interband links with topographic mapping and localization of equivalent dipole sources of individual EEG components, characteristic signs of changes in intercentral neuronal connections at different stages of a vegetative state were obtained, features of structural and functional interrelations for patients in a vegetative state in benzodiazepine test interpretation of which identification can represent and interest for the output prediction and selection of adequate therapy.

It has been studied the pharmacological effects of calcium channel blocking agents (CCBA), the derivatives of phenylalkilamin (verapamil), benzothiazepine (diltiazem), dihydropyridine (nifedipine) at a concentration of 0,1 mg/ml of the culture medium in the regulation of connective tissues development in the process of peritoneal adhesion. The experiments were carried out on 89 non-native white rats weighing 230-240 g on the 10th day after hemoperitoneum simulation in the primary culture of peritoneal fibroblasts and macrophages. It was specified that the development of peritoneal adhesion was accompanied by excessive proliferative activity of the cells studied with the enhancement of the synthesis of protein-bound oxyproline and hyaluronic acid, the pro-inflammatory cytokines, such as TNF-α and IL-1. Verapamil (0,1 mg/ml) suppressed the proliferation of fibroblasts, prevented the transformation of monocytes into macrophages, reduced the excess production of hydroxyproline and hyaluronic acid, and reduced the synthesis of pro-inflammatory cytokines. Diltiazem (0,1 mg/ml) had a normalizing effect on the functional activity of peritoneal fibroblasts and macrophages, the excess production of the intercellular matrix and cytokines, but the effect was less significant (on average 35,5 %, p <0,05) than in application of verapamil. In using of nifedipine (0,1 mg / ml) this effect was not detected