A Comparison of the Neuroprotective Efficacy of Newly Developed Oximes (K156, K203) and Currently Available Oximes (Obidoxime, HI-6) in Cyclosarin-poisoned Rats

Kassa, Jiřı́; Karasová, Jana Žďárová; Tesarova, Sandra; Kuča, Kamil; Musílek, Kamil

doi:10.14712/18059694.2017.27

Cited by 4 publications

(1 citation statement)

References 21 publications

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“…Recently, the oxime K203 [1-(4-carbamoylpyridinium)-4-(4-hydroxyiminomethylpyridinium)-but-2-ene dibromide] was synthesized at our Department of Toxicology (30) and its pharmacokinetics was studied (7). Based on in vitro and in vivo evaluation of its reactivating, therapeutic and neuroprotective efficacy, it was considered to be the promising oxime against tabun but not against cyclosarin and soman (11,12,14,15,16,19).…”

Section: Introductionmentioning

confidence: 99%

A Comparison of the Neuroprotective Efficacy of Individual Oximes (Hi-6, Trimedoxime, K203) and Their Mixtures (Hi-6 + Trimedoxime, Hi-6 + K203) in Cyclosarin-Poisoned Rats

Kassa¹,

Karasová²

2011

MMSL

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SummaryThe ability of three oximes (HI-6, trimedoxime, K203) to reduce cyclosarin-induced acute neurotoxic signs and symptoms was compared with the neuroprotective efficacy of two combinations of oximes (HI-6 + trimedoxime, HI-6 + K203) using a functional observational battery. Cyclosarin-induced neurotoxicity and the neuroprotective effects of HI-6, trimedoxime or K203 alone and HI-6 combined with trimedoxime or K203 in rats poisoned with cyclosarin at a sublethal dose (80 µg/kg i.m.; 70% of LD 50 value) were monitored by the functional observational battery at 24 hours and 7 days following cyclosarin challenge. The results indicate that all types of antidotal treatment are able to survive cyclosarin-poisoned rats 7 days following cyclosarin poisoning while one non-treated cyclosarin-poisoned rats died within 24 hours following cyclosarin challenge. All three oximes alone as well as both oxime mixtures combined with atropine were able to slightly decrease cyclosarin-induced neurotoxicity in the case of sublethal poisoning but they did not eliminate all cyclosarin-induced acute neurotoxic signs and symptoms. Their ability to reduce cyclosarininduced acute neurotoxicity was almost the same regardless of type of antidotal treatment. Thus, the tested combinations of oximes were not able to increase the neuroprotective effectiveness of antidotal treatment of acute cyclosarin poisoning compared to the individual oximes.

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Section: Introductionmentioning

confidence: 99%

A Comparison of the Neuroprotective Efficacy of Individual Oximes (Hi-6, Trimedoxime, K203) and Their Mixtures (Hi-6 + Trimedoxime, Hi-6 + K203) in Cyclosarin-Poisoned Rats

Kassa¹,

Karasová²

2011

MMSL

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Oxime K203: a drug candidate for the treatment of tabun intoxication

et al. 2018

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The influence of combinations of oximes on the reactivating and therapeutic efficacy of antidotal treatment of soman poisoning in rats and mice

Kassa

Karasová

Caisberger

et al. 2009

Toxicology Mechanisms and Methods

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The influence of the combination of oximes on the reactivating and therapeutic efficacy of antidotal treatment of acute soman poisoning was evaluated. The ability of two combinations of oximes (HI-6 + trimedoxime and HI-6 + K203) to reactivate soman-inhibited acetylcholinesterase and reduce acute toxicity of soman was compared with the reactivating and therapeutic efficacy of antidotal treatment involving single oxime (HI-6, trimedoxime, K203) using in vivo model. Studies determining percent of reactivation of soman-inhibited blood and diaphragm acetylcholinesterase in poisoned rats showed that the reactivating efficacy of both combinations of oximes is slightly greater than the reactivating efficacy of the most effective individual oxime, but the difference among them is not significant. Both combinations of oximes were found to be as effective in the reduction of acute lethal toxic effects in soman-poisoned mice as the antidotal treatment involving the most efficacious individual oxime. Thus, the efficacy of oximes is comparative in rats vs mice. A comparison of reactivating and therapeutic efficacy of individual oximes showed that the newly developed oxime K203 is approximately as effective as commonly used trimedoxime; nevertheless, their reactivating and therapeutic efficacy is markedly lower compared to the oxime HI-6. Based on the obtained data, one can conclude that the antidotal treatment involving chosen combinations of oximes does not significantly influence the potency of the most effective individual oxime (HI-6) to reactivate soman-inhibited rat acetylcholinesterase and to reduce acute toxicity of soman.

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A Comparison of the Neuroprotective Efficacy of Newly Developed Oximes (K156, K203) and Currently Available Oximes (Obidoxime, HI-6) in Cyclosarin-poisoned Rats

Cited by 4 publications

References 21 publications

A Comparison of the Neuroprotective Efficacy of Individual Oximes (Hi-6, Trimedoxime, K203) and Their Mixtures (Hi-6 + Trimedoxime, Hi-6 + K203) in Cyclosarin-Poisoned Rats

A Comparison of the Neuroprotective Efficacy of Individual Oximes (Hi-6, Trimedoxime, K203) and Their Mixtures (Hi-6 + Trimedoxime, Hi-6 + K203) in Cyclosarin-Poisoned Rats

Oxime K203: a drug candidate for the treatment of tabun intoxication

The influence of combinations of oximes on the reactivating and therapeutic efficacy of antidotal treatment of soman poisoning in rats and mice

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