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

Authors :
Teodorico C. Ramalho
Martina Hrabinova
Elaine F. F. da Cunha
Martin Vališ
Tanos C. C. França
Kamil Musilek
John Mikler
Alexandre A. de Castro
Ondrej Soukup
Eugenie Nepovimova
Daniel Jun
Jana Zdarova-Karasova
Kamil Kuca
Source :
BMC Pharmacology and Toxicology, Vol 19, Iss 1, Pp 1-10 (2018), BMC Pharmacology & Toxicology
Publication Year :
2018
Publisher :
BMC, 2018.

Abstract

Background 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. Methods 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). Results Reactivation studies showed that K203 was the most effective reactivator with a second order kinetic constant (k r) of 2142 min− 1. M− 1, which was 51 times higher than that obtained for obidoxime (k r = 42 min− 1. M− 1). Both pralidoxime and asoxime (HI-6) failed to significantly reactivate tabun-inhibited human AChE. Discussion 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.

Details

Language :
English
ISSN :
20506511
Volume :
19
Issue :
1
Database :
OpenAIRE
Journal :
BMC Pharmacology and Toxicology
Accession number :
edsair.doi.dedup.....c3a8ac53305d7d2ee2c9627be5873401