A newly developed oxime K203 is the most effective reactivator of tabun-inhibited acetylcholinesterase

BMC Pharmacology & Toxicology
Kamil KucaTeodorico C Ramalho

Abstract

Based on in vitro and in vivo rat experiments, the newly developed acetylcholinesterase (AChE) reactivator, K203, appears to be much more effective in the treatment of tabun poisonings than currently fielded oximes. To determine if this reactivating efficacy would extend to humans, studies were conducted in vitro using human brain homogenate as the source of AChE. The efficacy of K203 was compared with commercially available oximes; pralidoxime, obidoxime and asoxime (HI-6). Reactivation studies showed that K203 was the most effective reactivator with a second order kinetic constant (kr) of 2142 min- 1. M- 1, which was 51 times higher than that obtained for obidoxime (kr = 42 min- 1. M- 1). Both pralidoxime and asoxime (HI-6) failed to significantly reactivate tabun-inhibited human AChE. According to these results and previous studies, using K203, it appears that oxime K203 is the most effective reactivator of tabun-inhibited cholinesterase in several species including humans and should be considered as a possible medical countermeasure to tabun exposure.

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Citations

Nov 18, 2018·Chemistry : a European Journal·Andrew J FranjesevicChristopher M Hadad
Jun 9, 2020·Archives of Toxicology·Franz WorekTimo Wille
Sep 10, 2020·International Journal of Molecular Sciences·Alexandre A de CastroTeodorico C Ramalho
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Nov 14, 2020·Critical Reviews in Toxicology·Maria Alozi, Mutasem Rawas-Qalaji
Apr 24, 2021·Journal of Biomolecular Structure & Dynamics·İrfan Çapanİrfan Koca
Apr 28, 2021·Journal of Biomolecular Structure & Dynamics·Vishnu Kumar SharmaPrasad V Bharatam
Jun 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Li FengYazhou Wang
Jan 28, 2020·Journal of Chemical Information and Modeling·Felipe R S SantosJaqueline M S Ferreira
Dec 30, 2021·Journal of Biomolecular Structure & Dynamics·Nikitas GeorgiouThomas Mavromoustakos

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