Anderson D R, Harris L W, Lieske C N, Lennox W J
U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland 21010-5425.
Life Sci. 1991;48(25):2463-8. doi: 10.1016/0024-3205(91)90382-l.
To assess the utility of phosphinates as pretreatments against nerve agents, experiments were conducted to determine whether oximes can reactivate phosphinate-inhibited guinea pig acetylcholinesterase (AChE) and whether the toxicity of phosphinates is reduced by treatment with atropine and/or oxime. Three phosphinates, 4-nitrophenyl methyl(phenyl) phosphinate (MPP), 4-nitrophenyl chloromethyl(phenyl) phosphinate (CMPP), and 4-nitrophenyl 2-methoxyphenyl(methyl) phosphinate (MPMP), were used in these experiments. In the first group of experiments, 2-PAM or HI-6 was administered, im, 2 min after peak inhibition of whole blood AChE activity by the phosphinates. Both oximes significantly reactivated MPP- or CMPP-inhibited AChE; however, HI-6 was the better reactivator in both cases. Oximes were ineffective against MPMP. Efficacy studies revealed that neither HI-6 nor 2-PAM potentiated the toxic effects of MPP or CMPP and that atropine/oxime therapy provided greater protection (up to 100 LD50s) against either phosphinate than any single therapy. The reactivation and efficacy data, especially for CMPP, support the concept that oxime sensitive phosphinates may be useful as pretreatments against nerve agent intoxication.
为评估次膦酸盐作为神经毒剂预处理剂的效用，进行了实验以确定肟类化合物能否使被次膦酸盐抑制的豚鼠乙酰胆碱酯酶（AChE）重新活化，以及用阿托品和/或肟类化合物治疗是否能降低次膦酸盐的毒性。在这些实验中使用了三种次膦酸盐，即4-硝基苯基甲基（苯基）次膦酸酯（MPP）、4-硝基苯基氯甲基（苯基）次膦酸酯（CMPP）和4-硝基苯基2-甲氧基苯基（甲基）次膦酸酯（MPMP）。在第一组实验中，在次膦酸盐使全血AChE活性达到峰值抑制后2分钟，腹腔注射2-PAM或HI-6。两种肟类化合物均能显著使被MPP或CMPP抑制的AChE重新活化；然而，在这两种情况下HI-6都是更好的重新活化剂。肟类化合物对MPMP无效。疗效研究表明，HI-6和2-PAM均未增强MPP或CMPP的毒性作用，并且阿托品/肟类化合物疗法比任何单一疗法都能为抵抗这两种次膦酸盐提供更大的保护（高达100个半数致死剂量）。重新活化和疗效数据，尤其是关于CMPP的数据，支持了肟类敏感次膦酸盐可能作为神经毒剂中毒预处理剂有用的概念。
