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

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.

Keywords: Nerve agents; acetylcholinesterase; cholinergic transmission; development and deployment; drug development; treatment options.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acetylcholinesterase / pharmacology*
  • Animals
  • Chemical Warfare Agents / pharmacology*
  • Cholinesterase Inhibitors / pharmacology
  • Drug Development*
  • Humans
  • Nerve Agents / pharmacology*
  • Receptors, Nicotinic / drug effects*


  • Chemical Warfare Agents
  • Cholinesterase Inhibitors
  • Nerve Agents
  • Receptors, Nicotinic
  • Acetylcholinesterase