Biomedical subjects
Publications and source records attributed to E N Gorbatova.
Pentifin and dopamine D1 receptor antagonist SCH-23390 possess similar pharmacological properties. In the present work we studied in vitro effects of Pentifin on dopamine receptors. Experiments on rat ductus deferents showed that Pentifin acts as a weak ligand of dopamine receptors. Our results indicate that the antihaloperidol effect of Pentifin is not related to the blockade of dopamine receptors.
The modification of Bowman-Birk soybean protease inhibitor (BBI) with the monoaldehyde derivative of block copolymer of ethylene oxide and propylene oxide (PE), M(r) 2,000 is described. The conjugate contains five covalently bound polymer chains per protein molecule, and retains the ability to inhibit trypsin and chymotrypsin-like proteinases. The distribution of native BBI and the BBI-PE conjugate was examined in mice. After i.v. injection of [125I]BBI and [125I]BBI-PE, both inhibitors distributed very rapidly to the liver, kidney, and lungs, and more slowly to the brain. At the same time-points (up to 24 h), radioactivity in the blood and organs of mice injected with modified inhibitor was higher than that of the native inhibitor. The blood concentration time profile following i.v. administration of two BBI preparations at a dose 3 mg/kg was reasonable well described by a two-compartment open model with first-order elimination kinetics. The total clearance of BBI-PE decreased by a factor of 8, body mean residence time increased by a factor of 5 in comparison with BBI. A physiological pharmacokinetic model was developed to describe the tissue-to-blood distribution of two inhibitors. One-compartment physiological organ model (flow limited) was used to describe of time-course profiles of BBI concentration in organs. A two-compartment physiological organ model (membrane limited) was used to predict tissue-to-blood distribution of conjugated BBI in some organs of mice (liver, lungs). The predicted concentration curves of BBI and BBI-PE in blood and organs in mice (with the exception of kidney) showed good agreement with the observed values.
At present, there are no simple and reliable methods for selection of compounds with physiological activity in super-low concentrations (SLC). The screening system with high predictability is proposed. At the beginning, experiment is carried out on infusorians--spirostoma. Their motion activity, behavior, living ability and shape are registered at concentrations of substances in a range of 10(-3)-10(-13) mol/l. If the effect is detected on spirostoma, then experiments are performed on laboratory animals or their isolated tissues. Specific deviations on injection substance in SLC are detected, depending on compounds class. Nine representatives of different classes of biologically active compounds are investigated in the work: carbofos, deltametrin, 3-quinuclidinyl benzylate, atropine, phenosan, fenazepam, dopamine receptor antagonist SCH-23390, ciprine, and hexenal. It is accepted that if compound action in SLC is observed on spirostoma, then effects in super-low doses are also detected in a whole animal.
Explore the source record for details and available documents.
Explore the source record for details and available documents.