Department of Chemistry , The George Washington University , 800 22nd Street NW , Washington, DC 20052 , United States.
Computational Biology Institute , The George Washington University , 45085 University Drive Suite 305 , Ashburn , Virginia 20147 , United States.
ACS Chem Neurosci. 2018 May 16;9(5):873-885. doi: 10.1021/acschemneuro.8b00148. Epub 2018 Apr 25.
Nerve agents are organophosphorus chemical warfare agents that exert their action through the irreversible inhibition of acetylcholinesterase, with a consequent overstimulation of cholinergic transmission followed by its shutdown. Beyond warfare, they have notoriously been employed in acts of terrorism as well as high profile assassinations. After a brief historical introduction on the development and deployment of nerve agents, this review provides a survey of their chemistry, the way they affect cholinergic transmission, the available treatment options, and the current directions for their improvement. As the review illustrates, despite their merits, the currently available treatment options present several shortcomings. Current research directions involve the search for improved antidotes, antagonists of the nicotinic receptors, small-molecule pretreatment options, as well as bioscavengers as macromolecular pretreatment options. These efforts are making good progress in many different directions and, hopefully, will lead to a lower target susceptibility, thus reducing the appeal of nerve agents as chemical weapons.
神经毒剂是有机磷化学战剂，通过对乙酰胆碱酯酶的不可逆抑制发挥作用，随后导致胆碱能传递过度刺激及其关闭。除了战争用途，它们还臭名昭著地被用于恐怖主义行为和备受瞩目的暗杀事件中。在简要介绍了神经毒剂的开发和部署历史之后，本综述概述了它们的化学性质、对胆碱能传递的影响、可用的治疗选择以及针对它们的改进的当前方向。正如综述所说明的，尽管它们有优点，但目前可用的治疗选择存在几个缺点。当前的研究方向包括寻找改进的解毒剂、烟碱受体拮抗剂、小分子预处理选择，以及作为大分子预处理选择的生物清除剂。这些努力在许多不同的方向上都取得了良好的进展，希望这将降低目标易感性，从而降低神经毒剂作为化学武器的吸引力。
