各种模拟器对有机磷酸酯梭曼中毒的预防效果：构效关系研究

The prophylactic efficacy of various simulators against intoxication with the organophosphate soman: structure-activity studies.

作者信息

van Helden H P, Benschop H P, Wolthuis O L

出版信息

J Pharm Pharmacol. 1986 Jan;38(1):19-23. doi: 10.1111/j.2042-7158.1986.tb04460.x.

DOI:10.1111/j.2042-7158.1986.tb04460.x

Abstract

The effects were investigated of structural variations of the soman simulator pinacolyl dimethylphosphinate on its efficacy to prevent secondary failure of oxime-induced recovery of neuromuscular transmission and death after soman intoxication. The simulators were administered prophylactically to atropinized, HI-6 treated rats, dosed with 6 or 8 X LD50 soman. In these new simulators the pinacolyl moiety was varied, the phosphonyl oxygen atom was replaced by sulphur, or the phosphorous-bound methyl groups were replaced by ethyl or methoxy groups. All these variations appeared to be less active than pinacolyl dimethylphosphinate. Intravenously, the latter compound was very effective at a dose of 12 mumol kg-1; its i.v. LD50 appeared to be higher than 1 mmol kg-1.

摘要

研究了梭曼模拟物频哪基二甲基次膦酸酯的结构变化对其预防肟诱导的神经肌肉传递恢复继发性失败以及梭曼中毒后死亡的效果的影响。将这些模拟物预防性给予用阿托品处理、经HI-6治疗的大鼠，这些大鼠给予6或8倍半数致死量的梭曼。在这些新的模拟物中，频哪基部分有所变化，膦酰基氧原子被硫取代，或者与磷相连的甲基被乙基或甲氧基取代。所有这些变化似乎都比频哪基二甲基次膦酸酯的活性低。静脉注射时，后一种化合物在剂量为12 μmol·kg⁻¹时非常有效；其静脉注射半数致死量似乎高于1 mmol·kg⁻¹。