Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstrasse 11, 80937 Munich, Germany.
Toxicol Appl Pharmacol. 2011 May 15;253(1):7-13. doi: 10.1016/j.taap.2011.03.005. Epub 2011 Mar 11.
Standard treatment of organophosphorus (OP) poisoning includes administration of an antimuscarinic (e.g., atropine) and of an oxime-based reactivator. However, successful oxime treatment in soman poisoning is limited due to rapid aging of phosphylated acetylcholinesterase (AChE). Hence, the inability of standard treatment procedures to counteract the effects of soman poisoning resulted in the search for alternative strategies. Recently, results of an in vivo guinea pig study indicated a therapeutic effect of physostigmine given after soman. The present study was performed to investigate a possible pre- and post-treatment effect of physostigmine on soman-inhibited human AChE given at different time intervals before or after perfusion with soman by using a well-established dynamically working in vitro model for real-time analysis of erythrocyte and muscle AChE. The major findings were that prophylactic physostigmine prevented complete inhibition of AChE by soman and resulted in partial spontaneous recovery of the enzyme by de-carbamylation. Physostigmine given as post-treatment resulted in a time-dependent reduction of the protection from soman inhibition and recovery of AChE. Hence, these date indicate that physostigmine given after soman does not protect AChE from irreversible inhibition by the OP and that the observed therapeutic effect of physostigmine in nerve agent poisoning in vivo is probably due to other factors.
标准的有机磷（OP）中毒治疗包括使用抗毒蕈碱药物（如阿托品）和肟类再激活剂。然而，由于磷酰化乙酰胆碱酯酶（AChE）的快速老化，肟类治疗在梭曼中毒中的效果有限。因此，标准治疗程序无法对抗梭曼中毒的影响，导致人们寻找替代策略。最近，一项体内豚鼠研究的结果表明，在梭曼中毒后给予毒扁豆碱具有治疗作用。本研究旨在使用已建立的实时分析红细胞和肌肉 AChE 的动态体外模型，研究毒扁豆碱在梭曼灌流前后不同时间点给予对梭曼抑制的人 AChE 的预治疗和后治疗效果。主要发现是预防性毒扁豆碱可防止梭曼完全抑制 AChE，并通过脱氨基作用导致酶的部分自发恢复。作为后治疗给予的毒扁豆碱可导致对梭曼抑制的保护作用和 AChE 恢复的时间依赖性降低。因此，这些数据表明，在梭曼中毒后给予的毒扁豆碱不能保护 AChE 免受 OP 的不可逆抑制，并且在体内神经毒剂中毒中观察到的毒扁豆碱的治疗效果可能归因于其他因素。
