Wolfe A D, Blick D W, Murphy M R, Miller S A, Gentry M K, Hartgraves S L, Doctor B P
Division of Biochemistry, Walter Reed Army Institute of Research, Washington, D.C. 20307-5100.
Toxicol Appl Pharmacol. 1992 Dec;117(2):189-93. doi: 10.1016/0041-008x(92)90236-l.
Purified fetal bovine serum acetylcholinesterase (FBS AChE) and horse serum butyrylcholinesterase (BChE) were successfully used as single pretreatment drugs for the prevention of pinacolyl methylphosphonofluoridate (soman) toxicity in nonhuman primates. Eight rhesus monkeys, trained to perform Primate Equilibrium Platform (PEP) tasks, were pretreated with FBS AChE or BChE and challenged with a cumulative level of five median lethal doses (LD50) of soman. All ChE-pretreated monkeys survived the soman challenge and showed no symptoms of soman toxicity. A quantitative linear relation was observed between the soman dose and the neutralization of blood ChE. None of the four AChE-pretreated animals showed PEP task decrements, even though administration of soman irreversibly inhibited nearly all of the exogenously administered AChE. In two of four BChE-pretreated animals, a small transient PEP performance decrement occurred when the cumulative soman dose exceeded 4 LD50. Performance decrements observed under BChE protection were modest by the usual standards of organophosphorus compound toxicity. No residual or delayed performance decrements or other untoward effects were observed during 6 weeks of post-exposure testing with either ChE.
纯化的胎牛血清乙酰胆碱酯酶（FBS AChE）和马血清丁酰胆碱酯酶（BChE）已成功用作预防非人灵长类动物中甲基膦酸频那酯（梭曼）毒性的单一预处理药物。八只经过训练可执行灵长类动物平衡平台（PEP）任务的恒河猴，分别用FBS AChE或BChE进行预处理，然后接受累积剂量为五个半数致死剂量（LD50）的梭曼挑战。所有经胆碱酯酶预处理的猴子都在梭曼挑战中存活下来，且未表现出梭曼中毒症状。观察到梭曼剂量与血液胆碱酯酶中和之间存在定量线性关系。四只经AChE预处理的动物中，即使给予梭曼不可逆地抑制了几乎所有外源性给予的AChE，也没有一只动物的PEP任务表现下降。在四只经BChE预处理的动物中，当累积梭曼剂量超过4个LD50时，有两只动物出现了短暂的小幅度PEP表现下降。按照有机磷化合物毒性的通常标准，在BChE保护下观察到的表现下降幅度较小。在接触后6周的测试中，无论是哪种胆碱酯酶，均未观察到残留或延迟的表现下降或其他不良影响。
