Tripathi H L, Dewey W L
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0613.
J Toxicol Environ Health. 1989;26(4):437-46. doi: 10.1080/15287398909531267.
The LD50s and ED50s for inhibition of acetylcholinesterase (AChE) in whole mouse brain by DFP (diisopropylfluorophosphate), sarin (methylphosphonofluoridic acid 1-methyl ethyl ester), soman (methylphosphonofluoridic acid 1,2,2-trimethyl propyl ester), and tabun (dimethylphosphoramidocyanidic acid ethyl ester) were compared after iv administration. The LD50s of DFP, sarin, soman, and tabun in ICR (Institute for Cancer Research) mice were 3.40, 0.109, 0.042, and 0.287 mg/kg, respectively. The recovery of AChE activity in whole mouse brain after sub-LD50 doses of these agents was slow and did not reach control values by 14 d after iv administration. AChE activity was inhibited in a dose-dependent manner in whole mouse brain, as well as in six brain regions (cortex, hippocampus, striatum, midbrain, medulla-pons, and cerebellum). None of these brain areas appeared to be particularly sensitive to AChE inhibition. The ED50s for DFP, sarin, soman, and tabun for inhibition of AChE in whole mouse brain were approximately 19, 38, 69, and 66% of their respective LD50s. Because of the differential potencies between lethality and inhibition of AChE, it is concluded that the lethality of these agents is due to more factors than simply the inhibition of AChE within the brain.
静脉注射后，比较了二异丙基氟磷酸酯（DFP）、沙林（甲基氟膦酸异丙酯）、梭曼（甲基氟膦酸频那酯）和塔崩（二甲基氨基氰磷酸乙酯）对全小鼠脑乙酰胆碱酯酶（AChE）抑制作用的半数致死量（LD50）和半数有效量（ED50）。在ICR（癌症研究机构）小鼠中，DFP、沙林、梭曼和塔崩的LD50分别为3.40、0.109、0.042和0.287 mg/kg。静脉注射这些药物低于LD50剂量后，全小鼠脑AChE活性的恢复缓慢，在给药后14天未达到对照值。全小鼠脑以及六个脑区（皮层、海马体、纹状体、中脑、脑桥延髓和小脑）的AChE活性均呈剂量依赖性抑制。这些脑区似乎对AChE抑制均无特别敏感性。DFP、沙林、梭曼和塔崩对全小鼠脑AChE抑制的ED50分别约为其各自LD50的19%、38%、69%和66%。由于致死性和AChE抑制之间的效力差异，得出结论：这些药物的致死性不仅仅是由于脑内AChE的抑制，还涉及更多因素。
