Čes. slov. farm. 2005, 54(4):192-195

A Comparison of the Efficacy of the Reactivators of Acetylcholinesterase Inhibited with Tabun

J. Cabal, K. Kuča, D. Jun, J. Bajgar, M. Hrabinová

Univerzita obrany v Hradci Králové, Fakulta vojenského zdravotnictví, Katedra toxikologie

The nerve agent tabun inhibits acetylcholinesterase (AChE; EC 3.1.1.7) by the formation of a covalent bond with the enzyme. Afterwards, AChE is not able to fulfil its role in the organism and subsequently cholinergic crisis occurs. AChE reactivators (pralidoxime, obidoxime and HI-6) as causal antidotes are used for the cleavage of the bond between the enzyme and nerve agent. Unfortunately, their potency for reactivation of tabun-inhibited AChE is poor. The aim of the study was to choose the most potent reactivator of tabun-inhibited AChE. We have tested eight AChE reactivators - pralidoxime, obidoxime, trimedoxime, HI-6, methoxime, Hlö-7 and our newly synthesized oximes K027 and K048. All reactivators were tested using our standard in vitro reactivation test (pH 8, 25°C, time of inhibition by the nerve agent 30 minutes, time of reactivation by AChE reactivator 10 minutes). According to our results, only trimedoxime was able to achieve 50% reactivation potency. However, this relatively high potency was achieved at high oxime concentration (10^-2 M). At a lower concentration of 10^-4 M (the probably attainable concentration in vivo), four AChE reactivators (trimedoxime, obidoxime, K027, and K048) were able to reactivate AChE inhibited by tabun reaching from 10 to 18 %.

Keywords: acetylcholinesterase; reactivators; nerve agents; tabun; oxim

Received: January 19, 2005; Accepted: April 13, 2005; Published: April 1, 2005  Show citation