Nerve Agents: What They Are, How They Work, How to Counter Them

Abstract

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.

Screening for Improved Nerve Agent Simulants and Insights into Organophosphate Hydrolysis Reactions from DFT and QSAR Modeling

“…2019,25,[9217][9218][9219][9220][9221][9222][9223][9224][9225][9226][9227][9228][9229] www.chemeurj.org with an extra electron (N + 1) and the neutral molecule with N electrons [Eq. (7)]: [78]…”

“…This triggers continuous stimulation of muscles and glands, which can lead to asphyxiation and death. Nerve agents can be divided into three classes: G‐series agents, including sarin (GB), soman (GD), tabun (GA), and cyclosarin (GF); V‐series agents, including VX, VR, VE, VG, VS, and VM; and Novichok agents, such as A230, A232, and A234 . Research into methods and materials for the capture and decomposition of these lethal agents has been ongoing since their discovery .…”

“…Nerve agents can be divided into three classes:G -series agents, includings arin (GB), soman (GD), tabun( GA), and cyclosarin (GF); [5] V-series agents, including VX, VR, VE, VG, VS,a nd VM; [6] and Novichok agents, such as A230, A232, and A234. [7] Researchi nto methods and materials for the capture andd ecomposition of these lethala gents has been ongoing since their discovery. [8] Detoxification of nerve agents usually involves hydrolysis, with nucleophilic watero rh ydroxide substituting at the phosphorus atom of the agent,r esulting in elimination of the toxic leaving group( see Scheme 1).…”

Are Imidazoles Versatile or Promiscuous in Reactions With Organophosphates? Insights From the Case of Parathion

“…Albeit the use of chemical warfare seemed to be used only during world wars, they continue to be a prevailing risk since they have been used in terrorist attacks such as at the subway in Tokyo (1995), in the recent Syrian war and even in assassination attempts (Russian spy in 2018 in UK). 4 Hence, the overall development of efficient decontamination / monitoring systems is crucial to protect modern society. All these efforts rely primarily on the concise understanding of the reaction mechanisms involved, since they dictate the favorable pathways and indicate the less-toxic products.…”

Challenges in Fluorescence Detection of Chemical Warfare Agent Vapors Using Solid‐State Films

“…Among the CWAs, nerve agents are a family of highly toxic organophosphorus (OP) compounds . The main routes of exposure to OP compounds are via inhalation or dermal absorption and their mode of action is inhibition of the enzyme acetylcholinesterase (AChE), which is critical for hydrolyzing the neurotransmitter acetylcholine to control its concentration .…”