Organophosphate nerve agents

Young, Robert A.; Watson, A.P.

doi:10.1016/b978-0-12-819090-6.00008-8

Cited by 8 publications

(4 citation statements)

References 107 publications

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“…Knowledge of these values allows an initial rough estimation of the potential in vivo toxicity. However, the actual in vivo toxicity is determined by multiple interconnected factors including volatility, chemical and biological stability, lipophilicity and finally the route of exposure (Rice 2016;Young and Watson 2020).…”

Section: The Threatmentioning

confidence: 99%

Organophosphorus compounds and oximes: a critical review

Worek¹,

2020

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Organophosphorus (OP) pesticides and nerve agents still pose a threat to the population. Treatment of OP poisoning is an ongoing challenge and burden for medical services. Standard drug treatment consists of atropine and an oxime as reactivator of OP-inhibited acetylcholinesterase and is virtually unchanged since more than six decades. Established oximes, i.e. pralidoxime, obidoxime, TMB-4, HI-6 and MMB-4, are of insufficient effectiveness in some poisonings and often cover only a limited spectrum of the different nerve agents and pesticides. Moreover, the value of oximes in human OP pesticide poisoning is still disputed. Long-lasting research efforts resulted in the preparation of countless experimental oximes, and more recently non-oxime reactivators, intended to replace or supplement the established and licensed oximes. The progress of this development is slow and none of the novel compounds appears to be suitable for transfer into advanced development or into clinical use. This situation calls for a critical analysis of the value of oximes as mainstay of treatment as well as the potential and limitations of established and novel reactivators. Requirements for a straightforward identification of superior reactivators and their development to licensed drugs need to be addressed as well as options for interim solutions as a chance to improve the therapy of OP poisoning in a foreseeable time frame.

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Section: The Threatmentioning

confidence: 99%

Organophosphorus compounds and oximes: a critical review

Worek¹,

2020

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“…Organophosphorus chemicals (OPs) are highly toxic compounds inhibiting cholinesterase enzymes from the central nervous system and causing severe poisoning in humans [ 1 , 2 ]. They have been developed as organophosphorus nerve agents (OPNAs) for military purposes but have also been considered for use in agriculture and constitute the first class of insecticides worldwide responsible for severe acute and chronic intoxications [ 3 , 4 , 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Enzymatic Decontamination of G-Type, V-Type and Novichok Nerve Agents

Jacquet

Rémy

Bross³

et al. 2021

IJMS

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Organophosphorus nerve agents (OPNAs) are highly toxic compounds inhibiting cholinergic enzymes in the central and autonomic nervous systems and neuromuscular junctions, causing severe intoxications in humans. Medical countermeasures and efficient decontamination solutions are needed to counteract the toxicity of a wide spectrum of harmful OPNAs including G, V and Novichok agents. Here, we describe the use of engineered OPNA-degrading enzymes for the degradation of various toxic agents including insecticides, a series of OPNA surrogates, as well as real chemical warfare agents (cyclosarin, sarin, soman, tabun, VX, A230, A232, A234). We demonstrate that only two enzymes can degrade most of these molecules at high concentrations (25 mM) in less than 5 minutes. Using surface assays adapted from NATO AEP-65 guidelines, we further show that enzyme-based solutions can decontaminate 97.6% and 99.4% of 10 g∙m−² of soman- and VX-contaminated surfaces, respectively. Finally, we demonstrate that these enzymes can degrade ethyl-paraoxon down to sub-inhibitory concentrations of acetylcholinesterase, confirming their efficacy from high to micromolar doses.

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“…These agents can rapidly lead to clinical effects or death which depends on the agent, the route of exposure, and the absorbed amount of the agent . They are potent acetylcholinesterase-active agents and highlight a steep dose–response curve. , They may have various and different effects on the peripheral and central nervous systems with ocular, respiratory, gastrointestinal, systemic, or muscarinic effects. , Organophosphorous agents (OPs) can be classified into four types: (i) “G” agents (G stands for German agents), mostly represented by tabun, sarin, and soman, (ii) “V” agents (V stands for venomous), where the most known agents are VE, VG, VX, and Chinese VX, (iii) “GV” agents, which have the combined properties of both G and V agents, and (iv) Novichok agents. ,, Despite the existence of the Organization for the Prohibition of Chemical Weapons (OPCW), these toxic agents have been used not only on the battlefield in Iraq in 1984 but also more recently on civilians over the past 3 years. , …”

Section: Introductionmentioning

confidence: 99%

3D Core–Shell TiO₂@MnO₂ Nanorod Arrays on Microcantilevers for Enhancing the Detection Sensitivity of Chemical Warfare Agents

Thomas

Spitzer

2021

ACS Appl. Mater. Interfaces

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Nanostructured microcantilevers have shown promise for sensing application of molecules in the vapor phase. Nanostructures have improved the molecule capture ability of microcantilevers by highly enhancing the surface of capture. Here, to improve the sensitivity and selectivity of a commercial microcantilever without functionalization, we developed 3D core–shell titanium dioxide@manganese dioxide (TiO2@MnO2) nanorod arrays on a microcantilever, which exhibited a high enhancement in the sensing performance beyond that of 1D nanostructures for the detection of dimethyl methylphosphonate, a simulant of sarin.

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Organophosphate nerve agents

Cited by 8 publications

References 107 publications

Organophosphorus compounds and oximes: a critical review

Organophosphorus compounds and oximes: a critical review

Enzymatic Decontamination of G-Type, V-Type and Novichok Nerve Agents

3D Core–Shell TiO₂@MnO₂ Nanorod Arrays on Microcantilevers for Enhancing the Detection Sensitivity of Chemical Warfare Agents

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Organophosphate nerve agents

Cited by 8 publications

References 107 publications

Organophosphorus compounds and oximes: a critical review

Organophosphorus compounds and oximes: a critical review

Enzymatic Decontamination of G-Type, V-Type and Novichok Nerve Agents

3D Core–Shell TiO2@MnO2 Nanorod Arrays on Microcantilevers for Enhancing the Detection Sensitivity of Chemical Warfare Agents

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Product

Resources

About

3D Core–Shell TiO₂@MnO₂ Nanorod Arrays on Microcantilevers for Enhancing the Detection Sensitivity of Chemical Warfare Agents