Novichok agents: a historical, current, and toxicological perspective

@article{Chai2018NovichokAA,
  title={Novichok agents: a historical, current, and toxicological perspective},
  author={Peter Ray Chai and Bryan D Hayes and Timothy B. Erickson and Edward W. Boyer},
  journal={Toxicology communications},
  year={2018},
  volume={2},
  pages={45 - 48}
}
Abstract The Novichok, or “newcomer” class of nerve agents are lesser characterized, weaponized organophosphate agents. The use of known Novichok agents in warfare is banned under the Chemical Weapons Convention of 1997. Novichok agents are considered more potent than VX gas and can be applied in unitary and binary forms. Like other nerve agents, Novichok agents irreversibly bind acetylcholinesterase and produce a cholinergic toxidrome. Uniquely, these agents are thought to also target neurons… 

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References

SHOWING 1-10 OF 51 REFERENCES

Toxicity of organophosphate nerve agents and related phosphonylated oximes compared to their anticholinesterase activity in neuron cultures.

Comparative studies of O,O-dialkyl-O-chloromethylchloroformimino phosphates: interaction with neuropathy target esterase and acetylcholinesterase.

A quantitative structure-activity relationships (QSAR) analysis indicated that NTE and AChE have different structural and electronic requirements for their respective OP inhibitors, and extrapolation from in vitro to in vivo data now seems justifiable to predict risk of OPIDN.

SYNTHESIS AND STRUCTURE OF SOME PHOSPHONYLATED OXIMES RELATED TO ORGANOPHOSPHATE NERVE AGENTS

Abstract Oximes, and in particular oximate salts, can be useful nucleophiles for the treatment of organophosphate nerve agent poisoning and decontamination of chemical warfare agents. In this paper,

Toxic chemical weapons of assassination and warfare: nerve agents VX and sarin

Healthcare providers should recognize symptoms of nerve agent exposure, understand regional and international notification procedures for potential attacks, as well as the indications for and available supply of antidotal therapy.

Diphenhydramine as a protective agent in a rat model of acute, lethal organophosphate poisoning.

Dichlorvos exposure resulted in profound fasciculations within 2 minutes of injection in all cohorts, and diphenhydramine chloride significantly reduced mortality in rats with acute, severe dichlorVos exposure.

Handbook of Toxicology of Chemical Warfare Agents

QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS PREDICT THE DELAYED NEUROTOXICITY POTENTIAL OF A SERIES OF O-ALKYL-O-METHYLCHLOROFORMIMINO PHENYLPHOSPHONATES

Examination of in vivo and in vitro predictions of neuropathic potential indicate that valid predictive QSAR models may be based on the in vitro approach, and adoption of this system would result in reducing experimental animal use, lowering costs, accelerating data production, and enabling standardization of a biochemically based risk assessment of the neuropathy potential of OP compounds.

Formation of models of the interaction between organophosphate compound structure and their ability to inhibit cholinesterase

Computer modelling of relationships between structure of organophosphorous compounds and their anticholinesterase activity revealed some functional peculiarities of these compounds and allowed for rationalisation of search of effective compounds with anticholinergic activity.

[Formation of models of the interaction between organophosphate compound structure and their ability to inhibit cholinesterase].

This study revealed some functional peculiarities of organophosphorous compounds and allowed for rationalisation of search of effective compounds with anticholinesterase activity.
...