Porovnání účinků smrtné a maximální tolerované dávky standardních acetylcholinesterasových reaktivátorů

• Main Author: Žárská, Nikola
• Other Authors: Kovařík, Miroslav
• Format: Dissertation
• Language: Czech
• Published: 2019
• Online Access: http://www.nusl.cz/ntk/nusl-403252

Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Candidate Bc. Nikola Žárská Supervisor PharmDr. Miroslav Kovařík, Ph.D. Consultant Mgr. Martina Hrabinová Title of Thesis A comparison of lethal and maximum tolerated dose of standard acetylcholinesterase reactivators. Diploma thesis deals with the topic of nerve agents. Specifically, it demonstrates the reactivating effect of oxime HI-6 (at 100 % maximum tolerated dose and 5 % median lethal dose) on the acetylcholinesterase inhibited by sarin. The experiment was carried out in vivo in Balb/c mice. The treatment was administered either with oxime HI-6 alone, in the above- mentioned doses, or in combination with the parasympatholytic atropine. The change in activity of acetylcholinesterase was measured by spectrophotometrically method, modified by the Ellman, in blood and brain. There were no signs of sarin intoxication in mice, that where treated with 100 % maximum tolerated dose of HI-6, in compare to mice treated with atropine only and 5 % median lethal dose of HI-6, where the intoxication was observed. It was founded that after i.m administration of 100 % maximum tolerated dose, the HI-6 concentration reached 500 µM in plasma and 10 µM in brain. This concentration is safe, but for...