[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].
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.
Molochkina
E M
EM
Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, Moscow, 119991 Russia. molochkina@mail333.com
Ozerova
I B
IB
D000109:Acetylcholine / Q000494:pharmacology; D000110:Acetylcholinesterase / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D001569:Benzodiazepines; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D008815:Mice, Inbred Strains; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000145:classification; D010666:Phenylpropionates / Q000494:pharmacology
D014151:Anti-Anxiety Agents; D000975:Antioxidants; D004364:Pharmaceutical Preparations; D010666:Phenylpropionates; D001569:Benzodiazepines; C017928:phenazepam; D006861:Hydrogen Peroxide; D000110:Acetylcholinesterase; D000109:Acetylcholine; C047854:fenozan