Myhrer Trond, Mariussen Espen, Enger Siri, Aas Pål
Norwegian Defence Research Establishment (FFI), Protection and Societal Security Division, PO Box 25, No-2027 Kjeller, Norway.
Norwegian Defence Research Establishment (FFI), Protection and Societal Security Division, PO Box 25, No-2027 Kjeller, Norway.
Neurotoxicology. 2015 Sep;50:142-8. doi: 10.1016/j.neuro.2015.08.012. Epub 2015 Aug 28.
A treatment regimen consisting of HI-6, levetiracetam, and procyclidine (termed the triple regimen) has previously been shown to work as a universal therapy against soman poisoning in rats, since it has capacities to function as both prophylactic and therapeutic measure. The purpose of the present study was to examine whether the triple regimen may have antidotal efficacy against intoxication by other classical nerve agents than soman. The treatment was given 1 and 5 min after exposure to a supralethal dose of nerve agents, and the results showed that the triple regimen successfully prevented or terminated seizures and preserved the lives of rats exposed to 5×LD50 of soman, sarin, cyclosarin, or VX, but solely 3×LD50 of tabun was managed by this regimen. To meet the particular antidotal requirements of tabun, the triple regimen was reinforced with obidoxime and was made to a quadruple regimen that effectively treated rats intoxicated by 5×LD50 of tabun. The rats recovered very well and the majority gained pre-exposure body weight within 7 days. Neuropathology was seen in all groups regardless of whether the rats seized or not. The most extensive damage was produced by sarin and cyclosarin. Differentiation between the nerve agents' potency to cause lesions was probably seen because the efficacious treatments ensured survival of supralethal poisoning. A combination of 2 oximes and 2 anticonvulsants may be a prerequisite to counteract effectively high levels of poisoning by any classical nerve agent.
一种由HI-6、左乙拉西坦和丙环定组成的治疗方案(称为三联疗法)此前已被证明可作为大鼠抗梭曼中毒的通用疗法,因为它具有预防和治疗双重作用。本研究的目的是检验三联疗法对除梭曼以外的其他经典神经毒剂中毒是否具有解毒效果。在暴露于超致死剂量的神经毒剂后1分钟和5分钟给予治疗,结果表明,三联疗法成功预防或终止了癫痫发作,并挽救了暴露于5倍半数致死剂量(LD50)的梭曼、沙林、环沙林或VX的大鼠的生命,但该方案仅能应对3倍LD50的塔崩中毒。为满足塔崩的特殊解毒需求,三联疗法添加了双复磷,形成四联疗法,可有效治疗暴露于5倍LD50塔崩的大鼠。大鼠恢复良好,大多数在7天内恢复到暴露前的体重。无论大鼠是否发生癫痫,所有组均出现神经病理学变化。沙林和环沙林造成的损伤最为广泛。可能由于有效的治疗确保了超致死中毒后的存活,因此可以看出不同神经毒剂造成损伤的能力有所差异。两种肟类药物和两种抗惊厥药物的联合使用可能是有效对抗任何经典神经毒剂高剂量中毒的先决条件。