Kuca K, Hrabinova M, Soukup O, Tobin G, Karasova J, Pohanka M
Centre of Advanced Studies, Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Czech Republic.
Bratisl Lek Listy. 2010;111(9):502-4.
In this work, we aim to summarize the universality of this compound, its reactivation potential when different cholinesterase inhibitors are used.
Pralidoxime is considered as a gold standard of acetylcholinesterase reactivators--antidotes used in case of nerve agent poisonings. It has been commercially available for many years. However, several studies deem this oxime an old-fashion antidote.
Pralidoxime was synthesized at our department. The reactivating efficacy was tested on 10% (w/v) rat brain homogenate that had been incubated with appropriate inhibitor for 30 minutes to reach 96% inhibition of AChE. Then, pralidoxime was added for 10 minutes. Measurements were performed at 25 degrees C, pH 8, and 10(-3) and 10(-5) M concentrations of AChE reactivators. The activities of brain AChE were measured by a potentiostatic method.
No sufficient reactivation was achieved at the concentration of 10(-5) M, which is a concentration that can be reached after administration of therapeutic doses. At a higher dose (10(-3) M), pralidoxime reactivated AChE inhibited by paraoxon, chlorpyrifos, Russian VX, VX and sarin.
From the obtained results, it is clear that pralidoxime seems to be a poor reactivator of AChE inhibited by organophosphorous AChE inhibitors and thus cannot be labeled as a universal reactivator (Tab. 1, Fig. 3, Ref. 31).
在本研究中，我们旨在总结该化合物的通用性，以及使用不同胆碱酯酶抑制剂时其重新激活的潜力。
氯解磷定被认为是乙酰胆碱酯酶复活剂的金标准——用于治疗神经毒剂中毒的解毒剂。它已上市多年。然而，一些研究认为这种肟类药物是一种老式的解毒剂。
氯解磷定在我们科室合成。在10%（w/v）大鼠脑匀浆中测试其重新激活效力，该匀浆已与适当的抑制剂孵育30分钟，以使乙酰胆碱酯酶抑制率达到96%。然后加入氯解磷定10分钟。在25℃、pH 8以及乙酰胆碱酯酶复活剂浓度为10⁻³和10⁻⁵M的条件下进行测量。通过恒电位法测量脑乙酰胆碱酯酶的活性。
在10⁻⁵M浓度下未实现充分的重新激活，而该浓度可在给予治疗剂量后达到。在较高剂量（10⁻³M）下，氯解磷定可重新激活被对氧磷、毒死蜱、俄罗斯VX、VX和沙林抑制的乙酰胆碱酯酶。
从所得结果可以清楚地看出，氯解磷定似乎是一种对被有机磷乙酰胆碱酯酶抑制剂抑制的乙酰胆碱酯酶较差的重新激活剂，因此不能被标记为通用的重新激活剂（表1，图3，参考文献31）。
