Worek F, Eyer P, Aurbek N, Szinicz L, Thiermann H
Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstrasse 11, 80937 Munich, Germany.
Toxicol Appl Pharmacol. 2007 Mar;219(2-3):226-34. doi: 10.1016/j.taap.2006.10.001. Epub 2006 Oct 6.
The availability of highly toxic organophosphorus (OP) warfare agents (nerve agents) underlines the necessity for an effective medical treatment. Acute OP toxicity is primarily caused by inhibition of acetylcholinesterase (AChE). Reactivators (oximes) of inhibited AChE are a mainstay of treatment, however, the commercially available compounds, obidoxime and pralidoxime, are considered to be rather ineffective against various nerve agents, e.g. soman and cyclosarin. This led to the synthesis and investigation of numerous oximes in the past decades. Reactivation of OP-inhibited AChE is considered to be the most important reaction of oximes. Clinical data from studies with pesticide-poisoned patients support the assumption that the various reactions between AChE, OP and oxime, i.e. inhibition, reactivation and aging, can be investigated in vitro with human AChE. In contrast to animal experiments such in vitro studies with human tissue enable the evaluation of oxime efficacy without being affected by species differences. In the past few years numerous in vitro studies were performed by different groups with a large number of oximes and methods were developed for extrapolating in vitro data to different scenarios of human nerve agent poisoning. The present status in the evaluation of new oximes as antidotes against nerve agent poisoning will be discussed.
高毒性有机磷（OP）战剂（神经毒剂）的存在凸显了有效医学治疗的必要性。急性OP中毒主要是由乙酰胆碱酯酶（AChE）受到抑制所致。被抑制的AChE的重活化剂（肟类）是治疗的主要手段，然而，市售化合物双复磷和氯解磷定被认为对各种神经毒剂，如梭曼和环沙林，效果相当不佳。这导致在过去几十年中合成并研究了众多肟类。OP抑制的AChE的重活化被认为是肟类最重要的反应。农药中毒患者研究的临床数据支持以下假设：AChE、OP和肟之间的各种反应，即抑制、重活化和老化，可以用人AChE在体外进行研究。与动物实验不同，这种用人组织进行的体外研究能够在不受物种差异影响的情况下评估肟类的疗效。在过去几年中，不同团队用大量肟类进行了众多体外研究，并开发了将体外数据外推至人类神经毒剂中毒不同情形的方法。本文将讨论评估新型肟类作为神经毒剂中毒解毒剂的现状。
