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两种医学疗法在大鼠遭受高剂量梭曼中毒后不久非常有效,但只有一种具有普遍适用性。

Two medical therapies very effective shortly after high levels of soman poisoning in rats, but only one with universal utility.

机构信息

Norwegian Defence Research Establishment (FFI), Protection Division, P.O. Box 25, NO-2027 Kjeller, Norway.

出版信息

Toxicology. 2013 Dec 15;314(2-3):221-8. doi: 10.1016/j.tox.2013.08.005. Epub 2013 Aug 16.

Abstract

A treatment regimen consisting of HI-6, scopolamine, and physostigmine (termed the physostigmine regimen) has been based on the serendipitous discovery that it exerts powerful antidotal effects against high levels of soman poisoning if it is administered 1 min after exposure. A medical therapy with corresponding efficacy, but without the time limitation of the latter regimen, has been developed through studies of microinfusions of anticonvulsants into seizure controlling sites in the forebrain of rats. From these studies procyclidine emerged as the most potent anticonvulsant, and its potency was further enhanced when being combined with the antiepileptic levetiracetam during systemic administration. In the present study, the capacity of HI-6, levetiracetam, and procyclidine (termed the procyclidine regimen) was tested against that of the physostigmine regimen. The results showed that both regimens were very effective against supralethal doses of soman (3, 4, 5 × LD₅₀) when given 1 and 5 min after intoxication. When the treatments were administered 10 and 14 or 20 and 24 min after soman exposure, only the procyclidine regimen was able to terminate seizures and preserve lives. When used as prophylactic therapies, both regimens protected equally well against seizures, but only the procyclidine regimen provided neuroprotection. The procyclidine regimen has apparently capacities to serve as a universal therapy against soman intoxication in rats.

摘要

一种由 HI-6、莨菪碱和毒扁豆碱(称为毒扁豆碱方案)组成的治疗方案是基于一个偶然的发现,即在接触后 1 分钟内给予该方案,它对高水平的梭曼中毒具有强大的解毒作用。通过在前脑的癫痫控制部位对大鼠进行抗惊厥微输注的研究,开发出了一种具有相应疗效但没有后者方案时间限制的医学治疗方法。从这些研究中,普罗克利丁作为最有效的抗惊厥药脱颖而出,当与全身给予的抗癫痫药左乙拉西坦联合使用时,其效力进一步增强。在本研究中,HI-6、左乙拉西坦和普罗克利丁(称为普罗克利丁方案)的能力与毒扁豆碱方案进行了测试。结果表明,两种方案在中毒后 1 分钟和 5 分钟给予时,对超致死剂量的梭曼(3、4、5×LD₅₀)都非常有效。当在梭曼暴露后 10 分钟和 14 分钟或 20 分钟和 24 分钟给予治疗时,只有普罗克利丁方案能够终止癫痫发作并挽救生命。当用作预防性治疗时,两种方案对癫痫发作的保护作用相同,但只有普罗克利丁方案提供神经保护。普罗克利丁方案显然有能力作为大鼠梭曼中毒的通用治疗方法。

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