Distribution of acetylcholinesteraseś reactivators after intravenous administration.

Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Daniela Hnídková Supervisor: PharmDr. Marie Vopršalová, CSc. Title of diploma thesis: The monitoring of acetylcholinesterase reactivators distribution after intramuscular administration. Nerve agents belong to the group of OFI that irreversibly binds to acetylcholinesterase (AChE). Neurotransmitter acetylcholine (ACh) cannot be degraded and its increased concentration causes excessive overstimulation of cholinergic receptors, known as acute cholinergic crisis (Patočka et al., 2004). Reactivators of acetylcholinesterase, also called oximes, are causal antidotes for the treatment of OFI poisonings and therefore nerve agents. Their mechanism of action is to break bond between inhibitor and AChE active site and prevent its subsequent covalent binding (Šepsová, 2010). In this study pharmacokinetics of five selected reactivators of AChE (oxime HI-6, obidoxime, trimedoxime, oxime K203 and oxime K027) were monitored. Rats were used as a convenient model organism (male, tribe Wistar) for presented in vivo study. High Performance Liquid Chromatography (HPLC) was selected as the most suitable separation method to studied pharmacokinetics of oximes. In this study it was necessary to determine..