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三种新型双吡啶𬭩肟(K454、K456、K458)与肟 K203 和三甲氧基肟在 tabun 中毒的大鼠和小鼠中的再激活和治疗功效的评价。

The evaluation of the reactivating and therapeutic efficacy of three novel bispyridinium oximes (K454, K456, K458) in comparison with the oxime K203 and trimedoxime in tabun-poisoned rats and mice.

机构信息

Department of Toxicology, Faculty of Military Health Sciences , Trebesska 1575, 500 01 Hradec Kralove, Czech Republic.

出版信息

Toxicol Mech Methods. 2013 Feb;23(2):94-8. doi: 10.3109/15376516.2012.720304. Epub 2012 Oct 18.

Abstract

The potency of three newly developed bispyridinium compounds (K454, K456, K458) to reactivate tabun-inhibited acetylcholinesterase and reduce tabun-induced lethal toxic effects was compared with the oxime K203 and trimedoxime using in vivo methods. The study determining percentage of reactivation of tabun-inhibited diaphragm and brain acetylcholinesterase in poisoned rats showed that the reactivating efficacy of all newly developed oximes is comparable with K203 but lower than the reactivating potency of trimedoxime in diaphragm. In the brain, their potency to reactivate tabun-inhibited acetylcholinesterase is lower compared with trimedoxime and the oxime K203. All three newly developed oximes were also found to be relatively effective in reducing lethal toxic effects in tabun-poisoned mice. Their therapeutic efficacy is consistent with the therapeutic potency of the oxime K203. On the other hand, their potency to reduce acute toxicity of tabun is significantly lower compared with trimedoxime. In conclusion, the reactivating and therapeutic potency of all three newly developed oximes does not prevail the effectiveness of the oxime K203 and trimedoxime and, therefore, they are not suitable for their replacement of commonly used oximes for the treatment of acute tabun poisoning.

摘要

三种新开发的双吡啶化合物(K454、K456、K458)对沙林抑制的乙酰胆碱酯酶的重激活作用和降低沙林诱导的致死毒性效应的功效,与肟 K203 和trimedoxime 进行了比较,采用了体内方法。研究确定了中毒大鼠膈肌和脑乙酰胆碱酯酶的沙林抑制复能百分比,结果表明,所有新开发肟的复能功效与 K203 相当,但低于 trimedoxime 在膈肌中的复能效果。在大脑中,它们对沙林抑制的乙酰胆碱酯酶的复能效力低于 trimedoxime 和肟 K203。还发现这三种新开发的肟在降低沙林中毒小鼠的致死毒性效应方面也具有相对有效性。它们的治疗功效与肟 K203 的治疗效果一致。另一方面,与 trimedoxime 相比,它们降低沙林急性毒性的效力明显较低。总之,这三种新开发的肟的复能和治疗功效均不如肟 K203 和 trimedoxime 有效,因此不适合替代常用肟治疗急性沙林中毒。

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