The risk associated with organophosphorus nerve agents: from their discovery to their unavoidable threat, current medical countermeasures and perspectives.

Chem Biol Interact

Ecole de Chimie Polymère et Matériaux ECPM, Université de Strasbourg, ICPEES UMR CNRS 7515, 25 rue Becquerel, F-67087, Strasbourg, France; OPGS Pharmaceuticals, Paris BioTech Santé, 24 rue du Faubourg Saint-Jacques, F-75014, Paris, France. Electronic address:

Published: May 2024

AI Article Synopsis

  • * These nerve agents are highly lethal, targeting the nervous system by blocking an enzyme (AChE) that helps with neurotransmission, leading to severe health issues or death if not treated quickly.
  • * Research is focusing on developing better antidotes, such as modified reactivators that can cross the blood-brain barrier, to improve treatment for victims exposed to these toxic agents.

Article Abstract

The first organophosphorus nerve agent was discovered accidently during the development of pesticides, shortly after the first use of chemical weapons (chlorine, phosgene) on the battlefield during World War I. Despite the Chemical Weapons Convention banning these substances, they have still been employed in wars, terrorist attacks or political assassinations. Characterised by their high lethality, they target the nervous system by inhibiting the acetylcholinesterase (AChE) enzyme, preventing neurotransmission, which, if not treated rapidly, inevitably leads to serious injury or the death of the person intoxicated. The limited efficacy of current antidotes, known as AChE reactivators, pushes research towards new treatments. Numerous paths have been explored, from modifying the original pyridinium oximes to developing hybrid reactivators seeking a better affinity for the inhibited AChE. Another crucial approach resides in molecules more prone to cross the blood-brain barrier: uncharged compounds, bio-conjugated reactivators or innovative formulations. Our aim is to raise awareness on the threat and toxicity of organophosphorus nerve agents and to present the main synthetic efforts deployed since the first AChE reactivator, to tackle the task of efficiently treating victims of these chemical warfare agents.

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Source
http://dx.doi.org/10.1016/j.cbi.2024.110973DOI Listing

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