Sylant'yev S. Pharmacological Analysis of Fast-Reversible Effects of Ligands of GABA-Receptor Complex

The Dissertation is devoted to experimental study and structural & functional modelling of receptor - ligand interaction mechanisms taking place in an organism, carried out on the basis of investigation of the dynamics of minimum efficient doses of GABAА-mediatoric system of CNS ligands, as well as to grounding the ways to optimise the ligands' use. Based on investigation and mathematical modelling of convulsive effects of GABA-rc ligands -picrotoxine, bicuculline, pentilentetrazole, bemegride, as well as their mixtures, it was discovered, that when one of sub-units of GABA-receptor formed a complex with ligand, the formation modeled the functions of all its sub-units. The results of studies and mathematical modelling of effects of phenazepame, ethanol, natrium barbital, pentilentetrazole, picrotoxine, bicuculline permit us to state the existence of GABA-rc in minimum four functional-active conformations. On the basis of analysis and mathematical modelling of the effects of phenazepame, 3-oxyphenazepame, tetrohydrophenazepame, diazepamme, bromnordiazepame, hydazepame, cinazepame it is shown that the most adequate parameter characterising phar-macological effects of GABA-receptor is ED^ of its ligands. Methods of analysis and derivation of general form equation enabling us to calculate therapeutic index (indicator of safety of use) of the medicinal mixture and optimise it on the basis of experimental data are substantiated.