Phenazepam in therapeutic and ultralow doses in vitro modulates the content of lipid peroxidation products and acetylcholinesterase activity in membrane fraction from mouse brain.

In vitro incorporation of tranquilizer phenazepam in a concentration of 10(-13) M into membrane fraction from mouse brain produced a prooxidant effect. In concentrations of 10(-5)-10(-9) and 10(-15)-10(-17) M this agent possessed antioxidant activity. Phenazepam significantly decreased the maximum rate of enzymatic reactions (10(-5) and 10(-15) M) and Michaelis constant (10(-5) M) for acetylcholinesterase. Incorporation of phenazepam in ultralow doses into membrane modified its lipid components (estimated by lipid peroxidation) and functional state, and this effect was comparable with the influence of this substance in standard doses. This probably contributes to the physiological effect of ultralow doses of phenazepam in.

[The influence of pharmacologically active substances of different classes at ultra low doses on lipid peroxidation in brain cell membranes and activity of acetylcholinesterase in vivo and in vitro]. / Vliianie farmakologicheski aktivnykh veshchestv raznykh klassov v ul'tramalykh dozakh na peroksidnoe okislenie lipidov v kletochnykh membranakh golovnogo mozga i aktivnost' atsetilkholinésterazy in vivo i in vitro.

One of the approaches to the development of new medicines now is the exploration of the effects of low and ultra low doses (ULD) of biologically active substances and preparations traditionally used in rather high dosages. The purpose of our work was to investigate the influence of pharmacologically active substances of various classes at wide range of concentrations, including ultra low, on lipid peroxidation in cell membranes of mice brain and activity of acetylcholinesterase (AChE). The action of synthetic antioxidant (AO) from the group of hindered phenols (inhibitors of free-radical reactions) phenozan, neurotransmitter acetylcholine (ACh), hybrid compound "phenozan + ACh + alkyl radical C-10" (perspective for Alzheimer's disease therapy), tranquilizer from benzodiazepines phenazepam and hydrogen peroxide were investigated. The influence of the investigated substances at ULD (concentrations) on kinetic parameters of the reaction, catalysed with soluble and membrane AChE (Michaelis constant and maximal velocity), and also on lipid peroxidation (LPO) system (level of products and LPO velocity, contents of total lipids, phospholipids, cholesterol) in mice brain cell membranes in vitro and in vivo was revealed. Concentrational and dose curves were of compilated character with the presence of zero effect zones typical for the agents capable to work at ULD. The effects of super low and "usual" doses of investigated substances were commensurable.

[The characteristics of the biological action of low doses of irradiation]. / Osobennosti biologicheskogo deistviia malykh doz oblucheniia.

Biochemical, biophysical and functional properties of the genetic and membrane apparatus of the cell were considered activity and regulatory properties of the membrane and cytosolic enzymes of organs and tissues of mice exposed to radiation in the wide range of doses of 6 to 1800 mGy with the radiation intensity of 4.1 x 10(-3) and 41 x 10(-3) mGy/min. It was shown that the dose-dependence of changes in the investigated properties is of non-linear polymodal (bimodal) nature. The value of the maximum and the dose at which the latter was observed depend on the object's nature, radiation intensity and time passed after irradiation. An essential factor is that sensitivity of molecules, cells, organs and animals exposed to low-dose radiation to other damaging effects changes. The explanation is given in terms of the changes in the relation between the quantity of damages and the activity of reparation systems induced by low-dose irradiation.

[The biochemical changes in the brain synaptosomes during the gamma irradiation of mice at a low dose with different intensities]. / Biokhimicheskie izmeneniia v sinaptosomakh golovnogo mozga pri gamma-obluchenii myshei maloi dozoi s raznoi intensivnost'iu.

Some characteristics of mice brain nerve-endings' lipid phase were studied (total lipids, total and individual phospholipids and cholesterol contents, their ratios, lipid peroxidation level, rigidity index) after single low dose, whole body gamma-irradiation (15 cGy) with dose intensities of 0.01, 0.25, 9.0 cGy/min. Some markedly expressed alterations were found out in those parameters. Brain membranes functioning also changed significantly as it was judged by membrane-bound acetylcholinesterase activity. All the changes revealed complicated dependence both on dose intensity and on time period after irradiation. The ranges of the observed changes suppose CNS state to have been modified by low dose irradiation including CNS sensibility to external psycho- and neurotrophic factors.

[Effects of magnesium and nickel ions on penicillin-induced focal epileptic activity in the cerebral cortex of rats]. / Vliianie ionov magniia i nikelia na fokal'nuiu penitsillin-indutsirovannuiu épilepticheskuiu aktivnost' v kore golovnogo mozga krys.

In experiments on freely moving male Wistar rats on the model of penicillin-induced focal epileptic activity (EA) (the application onto the sensorimotor cortex of a filter paper soaked with benzylpenicillin sodium salt solution) it was shown that addition of MgSO4 (series 1) and NiCl2 (series 2) into the solution of penicillin significantly weakened EA. The combination of Mg2+ and Ni2+ with penicillin (series 3) produced a more significant suppression of EA as compared with separate application of the above-mentioned ions: the latency period of appearance of interictal discharges (IID) increased, the frequency and amplitude of IID decreased much more, no ictal discharges appeared in any animal, the duration of epileptic foci reduced to a much greater extent. This effect can be explained by the blockade of Ca current by the above-mentioned ions. One can suppose that the amplification of antiepileptic effects of combined action of Mg2+ and Ni2+ was due to an increase in the number of blocked voltage-dependent and NMDA-operated calcium channels.