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Molecules 2017, 22(7), 1152; doi:10.3390/molecules22071152

The Evaluation of the Reactivating and Neuroprotective Efficacy of Two Newly Prepared Bispyridinium Oximes (K305, K307) in Tabun-Poisoned Rats—A Comparison with Trimedoxime and the Oxime K203

1
Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences, University of Defense, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic
2
Clinic of Neurology, Faculty Hospital Hradec Kralove, Sokolovska 581, 500 01 Hradec Kralove, Czech Republic
*
Author to whom correspondence should be addressed.
Academic Editors: Anthony H. Futerman, Yacov Ashani, Gabriel Amitai and Lev Weiner
Received: 19 June 2017 / Revised: 4 July 2017 / Accepted: 5 July 2017 / Published: 11 July 2017
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Abstract

The ability of two newly developed oximes (K305, K307) to protect tabun-poisoned rats from tabun-induced inhibition of brain acetylcholinesterase, acute neurotoxic signs and symptoms and brain damage was compared with that of the oxime K203 and trimedoxime. The reactivating and neuroprotective effects of the oximes studied combined with atropine on rats poisoned with tabun at a sublethal dose were evaluated. The reactivating efficacy of a newly developed oxime K305 is lower compared to the reactivating efficacy of the oxime K203 and trimedoxime while the ability of the oxime K307 to reactivate tabun-inhibited acetylcholinesterase (AChE) in the brain roughly corresponds to the reactivating efficacy of the oxime K203 and it is slightly lower compared to trimedoxime. In addition, only one newly developed oxime (K307) combined with atropine was able to markedly decrease tabun-induced neurotoxicity although it did not eliminate all tabun-induced acute neurotoxic signs and symptoms. These results correspond to the histopathological evaluation of tabun-induced brain damage. Therefore, the newly developed oximes are not suitable for the replacement of commonly used oximes (especially trimedoxime) in the treatment of acute tabun poisonings. View Full-Text
Keywords: tabun; acetylcholinesterase; neurotoxicity; functional observational battery; histopathology; oximes; rats tabun; acetylcholinesterase; neurotoxicity; functional observational battery; histopathology; oximes; rats
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MDPI and ACS Style

Kassa, J.; Misik, J.; Hatlapatkova, J.; Zdarova Karasova, J.; Sepsova, V.; Caisberger, F.; Pejchal, J. The Evaluation of the Reactivating and Neuroprotective Efficacy of Two Newly Prepared Bispyridinium Oximes (K305, K307) in Tabun-Poisoned Rats—A Comparison with Trimedoxime and the Oxime K203. Molecules 2017, 22, 1152.

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