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A comparison of the reactivating and therapeutic efficacy of newly developed bispyridinium oximes (K250, K251) with commonly used oximes against tabun in rats and mice
Authors:Jiri Kassa  Jana Karasova  Jiri Bajgar  Kamil Kuca  Kamil Musilek  Irena Kopelikova
Affiliation:1. Department of Toxicology, Faculty of Military Health Sciences, Hradec Kralove, Czech Republickassa@pmfhk.cz;3. Department of Toxicology, Faculty of Military Health Sciences, Hradec Kralove, Czech Republic;4. Center of Advanced Studies, Faculty of Military Health Sciences, Hradec Kralove, Czech Republic;5. Faculty of Pharmacy, Charles University, Hradec Kralove, Czech Republic
Abstract:The potency of newly developed bispyridinium compounds (K250, K251) in reactivating tabun-inhibited acetylcholinesterase and reducing tabun-induced lethal toxic effects was compared with currently available oximes (obidoxime, trimedoxime, the oxime HI-6) using in vivo methods. Studies determined percentage of reactivation of tabun-inhibited blood and tissue AChE in poisoned rats and showed that the reactivating efficacy of both newly developed oximes is comparable with the oxime HI-6 but it is significantly lower than the reactivating effects of obidoxime and trimedoxime, especially in diaphragm and brain. Both newly developed oximes were also found to be able to slightly reduce lethal toxic effects in tabun-poisoned mice. Their therapeutic efficacy is higher than the potency of the oxime HI-6 but it is lower than the therapeutic effects of trimedoxime and obidoxime. Thus, the reactivating and therapeutic potency of both newly developed oximes (K250, K251) does not prevail over the effectiveness of currently available oximes and, therefore, they are not suitable for their replacement for the treatment of acute tabun poisoning.
Keywords:tabun  inhibited acetylcholinesterase  reactivation  K250  K251  obidoxime  trimedoxime  HI-6
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