Matzke S M, Oubre J L, Caranto G R, Gentry M K, Galbicka G
Walter Reed Army Institute of Research, Washington, DC 20307-5100, USA.
Pharmacol Biochem Behav. 1999 Mar;62(3):523-30. doi: 10.1016/s0091-3057(98)00183-x.
Although conventional therapies prevent organophosphate (OP) lethality, laboratory animals exposed to such treatments typically display behavioral incapacitation. Pretreatment with purified exogenous human or equine serum butyrylcholinesterase (Eq-BuChE), conversely, has effectively prevented OP lethality in rats and rhesus monkeys, without producing the adverse side effects associated with conventional treatments. In monkeys, however, using a commercial preparation of Eq-BuChE has been reported to incapacitate responding. In the present study, repeated administration of commercially prepared Eq-BuChE had no systematic effect on behavior in rhesus monkeys as measured by a six-item serial probe recognition task, despite 7- to 18-fold increases in baseline BuChE levels in blood. Antibody production induced by the enzyme was slight after the first injection and more pronounced following the second injection. The lack of behavioral effects, the relatively long in vivo half-life, and the previously demonstrated efficacy of BuChE as a biological scavenger for highly toxic OPs make BuChE potentially more effective than current treatment regimens for OP toxicity.
尽管传统疗法可预防有机磷酸酯（OP）致死，但接受此类治疗的实验动物通常会出现行为能力丧失。相反，用纯化的外源性人或马血清丁酰胆碱酯酶（Eq-BuChE）进行预处理，已有效预防了大鼠和恒河猴的OP致死，且未产生与传统治疗相关的不良副作用。然而，据报道，在猴子中使用商业化制备的Eq-BuChE会使反应能力丧失。在本研究中，通过六项连续探针识别任务测量，重复给予商业化制备的Eq-BuChE对恒河猴的行为没有系统性影响，尽管血液中基线丁酰胆碱酯酶水平增加了7至18倍。首次注射后，酶诱导的抗体产生轻微，第二次注射后更为明显。缺乏行为影响、相对较长的体内半衰期以及先前证明的丁酰胆碱酯酶作为高毒性OP生物清除剂的功效，使得丁酰胆碱酯酶在治疗OP毒性方面可能比目前的治疗方案更有效。
