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

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.

A comparison of the reactivating and therapeutic efficacy of two novel bispyridinium oximes (K920, K923) with the oxime K203 and trimedoxime in tabun-poisoned rats and mice

“…Both newly developed oximes (K920, K923) were designed as reactivators with aromatic connecting linker that was formerly found to be beneficial for the reactivation of organophosphorus compounds in vitro and in vivo (Musilek et al, 2007(Musilek et al, , 2010Nurulain et al, 2009). In addition, the oxime K923 was designed with ethoxycarbonyl moiety as a representative of carboxylic derivatives that were formerly found to decrease toxicity of the reactivator (Kassa et al, 2009). Our results demonstrate that the potency of both newly developed bispyridinium oximes (K920 and K923) administered at the selected doses to reactivate tabun-inhibited AChE and reduce tabun-induced acute toxicity is relatively low and it does not achieve the efficacy of trimedoxime and the oxime K203. One reason for their weak effectiveness is their high toxicity.…”

Design, evaluation and structure—Activity relationship studies of the AChE reactivators against organophosphorus pesticides

“…75,76,[78][79][80] Indeed, from a toxicity point of view, the carbamoyl, carboxyl, and methylcarbonyl moieties (259-260, 265) were found to be very promising candidates. 77,[102][103][104] …”

A Comparison of the Reactivating and Therapeutic Efficacy of Two Newly Developed Oximes (K727 and K733) with Oxime K203 and Trimedoxime in Tabun‐Poisoned Rats and Mice

“…Both newly developed bispyridinium oximes (K727 and K733) were designed as reactivators with aromatic connecting linker that was formerly found to be beneficial for the reactivation of cyclosarin, tabun and organophosphorus pesticides in vitro and in vivo . In addition, oxime K733 was designed with ethoxycarbonyl moiety as a representative of carboxylic derivatives that were previously found to decrease toxicity of the reactivator . Therefore, oxime K733 showed markedly lower acute toxicity than oxime K727.…”