In the paper presents the results of investigations pharmacokinetics a new dipeptyds neuropsychotropics drugs modyficated analogues of endogenics neuropeptids analizes in posishin of pharmacokinetics their comparable wich endogenics neuropeptids and metodical pathways of their pharmacokinetics impruwds on the studium of creating substation of dipeptids also on the sudium creating of oral drug forms.

The alcohol leads to deviant behavior in animals, increases aggression and irreversible degenerative changes in the liver and in the central nervous system. Lithium ascorbate in dose of 5 mg/kg, as well as higher doses (10 and 30 mg/kg), activates adaptive mechanisms normalizing behavioral responses in the tests «open field» and «elevated plus-maze». Histological analysis showed that lithium ascorbate minimize ischemic damage of neurocytes to a reversible state. In general, the use of lithium ascorbate contributes to relief of withdrawal symptoms, inhibited the occurrence of seizures and contributed to preservation of the function of the central nervous system in the model of chronic alcohol intoxication.

Novel derivative of benzoylpyridine oximes - GIZH-298 (4-benzoylpyridine 0-(2-morpholinoethyl) oxime oxalate) was designed and synthesized in this work. This compound has a broad spectrum of anticonvulsant effects, eliminating primary generalized seizures in maximal electroshock (MES) and corazol antagonism tests in rodents in the doses of 0,5-100 mg/kg. LD₅₀ for compound GIZH-298 is 316 mg/kg intraperitoneally (mouse). GIZH-298 has a large therapeutic breadth.

Systems biology analysis of over 700 magnesium-dependent proteins in human proteome shown that these proteins affect (1) the embryonic development, (2) energy metabolism, (3) signal transduction processes from receptors, (4) neurological function, (5) support of connective tissue structure, (6) cardiovascular and (7) immunological roles. Magnesium deficiency during pregnancy will stimulate deveLopment of congential maLformations (skeletal defects, rickets, hernia of the diaphragm, facial defects, craniosynostosis, structural disorders of the retina and vision, brachydactyly). Magnesium deficiency at an early age is associated with sudden death syndrome in preschool and adolescence leads to impaired function of skeletal muscles and myocardium. Magnesium deficiency is also characterized by mitochondrial disorders, hyperinsulinemia, disorders of the skin structure and its appendages, tumors and diseases associated with impaired energy metabolism (including hypoparathyroidism and anemia). Effects of magnesium deficiency in children significantly heavier on the background of lack of vitamin B₆ (pyridoxine). The results of proteomic analysis enable to point out the reLevant molecular and physiologicaL mechanisms of synergy between magnesium and pyridoxine. Overall, the results of the analysis indicate a very extensive area for the correction of magnesium and pyridoxine deficiency for the prevention and treatment of a wide range of diseases, from the period of fetal development and earLy chiLdhood through adolescence.

Group B vitamins are characterized by neuroprotective effects. Mechanisms of action of synergistic combinations of various vitamins are insufficiently studied. In this study, proteins with activity or levels dependent on vitamins B₁ (thiamine), B₆ (pyridoxine) and B₁₂ (cyanocobalamin) were found in genomic and proteomic databases. Systems biology analysis showed that the thiamine is necessary for synthesis of ATP (glucose metabolism, lipid and branched chain amino acids), hemopoiesis and maintenance of neuronal structure. Pyridoxine-dependent proteins of the proteome are necessary for the metabolism of amino acids, ATP synthesis, synthesis of neurotransmitters and of neuronal membranes. Vitamin B₁₂ is needed for the metabolism of lipids, hemopoiesis and shows neuroprotective and neurotrophic effects. We identified numerous synergistic interactions of vitamins B₁, B₆, B₁₂, at the molecular level, including the metabolism of amino acids, carbohydrates, lipids, forming structures of neurons, blood, ATP synthesis etc. The established mechanisms of vitamins B₁, B₆, B₁₂ synergy at the molecular level are of fundamental importance for neuroprotection and prevention of cerebrovascular disease.

Pharmacokinetic study of а new original anxiolytic drug GB-115, developed on the basis of endogenous tetrapeptide cholecystokinin, in healthy volunteers was performed. Volunteers were received drug as single 1, 3, 7, 11 or 15 mg tablets. The parent drug in the human blood plasma was detected within 2-6 hours after ingestion. Cmax/AUC0-T for doses 3-15 mg were averaged 0,482-0,552 h^-1. C_max were averaged from 7,29±2,83 ng/ml (for dose 1 mg) to 44,02±13,23 ng/ml (for dose 15 mg). Half-life of the drug is changed in the range of 0,6-1,0 h. Vd/F amounted to an average of 2,47 l/kg. Summarizing the obtained results it can be concluded that consistent, linear increase in the dose of GB-115 from 1 to 15 mg there is an increase in dose-dependent pharmacokinetic parameters. In the studied range of doses pharmacokinetics of GB-115 was linear.

Pharmacokinetic study of prolonged release capsules of mebeverine was carried out on 24 volunteers. It is known that the drug substance is completely metabolized due to first-pass effect. Therefore, pharmacokinetic parameters of the main metabolites -mebeverine acid and desmethyl mebeverine acid were measured. Bioanalytical method was developed to measurement of concentrations of these metabolites in blood plasma by using HPLC-MS/MS.