Toxicology: Effects: Nerve Agents are the most toxic of the known chemical agents. Liquids or vapors from these agents are hazardous and can cause death within minutes after exposure. Nerve Agents disrupt the function of the nervous system by interfering with the enzyme acetylcholinesterase. The major effects will be on skeletal muscles, certain organs, and the central nervous system. These compounds are similar to, but much more deadly than, agricultural organophosphate pesticides. Pathways: "G" series Nerve Agents are hazardous through inhalation, skin and eye exposure, ingestion, and abraded skin (e.g., breaks in the skin or penetration of skin by debris). /"G" Series Nerve Agents/
To date, treatment of organophosphate (OP) poisoning shows several shortcomings, and OP-victims might suffer from lasting cognitive deficits and sleep-wake disturbances. In the present study, long-term effects of soman poisoning on learning ability, memory and neurogenesis were investigated in rats, treated with the anticholinergic atropine and the oxime HI-6 for reactivation of soman-inhibited acetylcholinesterase. /The authors/ also investigated whether sub-chronic treatment with the reported neurogenesis enhancer olanzapine would stimulate neurogenesis and possibly normalize the anticipated long-term deleterious effects of soman intoxication. Animals were treated with HI-6 (125 mg/kg i.p.), followed after 30 min by soman (200 ug/kg s.c.) and atropine sulphate (16 mg/kg i.m.) 1 min thereafter. Soman poisoning led to an elevation of extracellular acetylcholine levels to 1500% over baseline values as assessed by striatal microdialysis. Brain acetylcholinesterase was inhibited over 95%. This was accompanied by short recurrent seizures lasting for 40 min. Osmotic minipumps releasing olanzapine (7.5 mg/kg/day) or vehicle were subcutaneously implanted 24 hr post-intoxication. After drug delivery for 4 weeks, newborn cells were BrdU labeled. Learning and memory performance were assessed 8 weeks after soman poisoning, followed by analysis of surviving newborn cells (BrdU) and neurogenesis (doublecortin, DCX). Eight weeks after soman-intoxication a significantly impaired learning ability was found that was paralleled by significantly lower numbers of DCX-positive cells but no changes in the number of BrdU-labeled cells. Apparently, the present Olanzapine regime was ineffective. /The authors/ conclude that soman poisoning has long lasting effects on learning ability, a finding that was accompanied by impaired neurogenesis. /They/ confirm a correlation between impaired neurogenesis and cognitive deficits...
Nerve agents irreversibly inhibit acetylcholinesterase (AChE), leading to cholinergic crisis and death at acute exposure levels. The complexity, delayed onset, and persistent nature of nerve agent induced CNS effects need to be elucidated to block their multiple effects. In the present study gene expression and phosphoprotein profile of certain key neuronal proteins were studied after soman exposure. Quantitative real time PCR analysis of c-Fos, Bax, CREB and caspase 3 genes in the hippocampus, cortex and cerebellum showed that only c-Fos and Bax mRNA expression was increased significantly. Western blot analysis also confirmed the induction of c-Fos at early time points both at 0.5 and 1.0 LD(50) dose of soman exposure. Acute soman exposure caused perturbations in the phosphorylation status of ERK, JNK, p38 MAPK, CREB, c-Jun and NF-?B in all the three brain regions. The primary target for soman toxicity, AChE was inhibited in blood and brain up to 90%. Therapeutic treatment comprising of HI-6, atropine and diazepam has completely protected animals from death and reactivated soman inhibited AChE up to 40% in the plasma and RBC. This therapeutic regime also reduced soman induced Bax expression to near control levels, but could not reverse the soman induced changes in c-Fos expression and phosphorylation levels completely. Results suggest that exposure to soman caused persistent changes in these key brain proteins, which could lead to the development of complex neurotoxic effects and there is an urgent need for development of better drugs to stop multiple effects of nerve agents poisoning.
/G-agents/ are ... readily absorbable through not only the lung and eyes but also the skin and intestinal tract without producing any irritation or other sensation on the part of the exposed individual. /G-agents, SRP: such as soman/
Blood levels of the four stereoisomers of the nerve agent C(+/-)P(+/-)-soman were analyzed gas chromatographically in anesthetized, artificially respirated and atropinized rats, guinea pigs and marmosets at iv doses of C(+/-)P(+/-)-soman corresponding with 1-6 LD50. The relatively nontoxic C(+/-)P(+/-)-isomers disappear within a few minutes from the blood stream of all three species, whereas the levels of the highly toxic C(+/-)P(-)-isomers remain toxicologically relevant for periods of 50-100 min in three species of doses of 2-3 LD50. Elimination pathways were quantified using carbon-14 labeled soman stereoisomers. Whereas the C(+/-)P(+)-isomers are largely eliminated by way of enzymatic hydrolysis, the major elimination pathway for the C(+/-)P(-)-isomers is binding to various proteins, in competition with binding to target acetylcholinesterase. Intraspecies nonlinearity with dose in the toxicokinetics of the C(+/-)P(-)-isomers is related to heterogeneous reactivity of the binding sites. Interspecies nonlinearity is probably due to decreasing amounts of binding sites in the order rats greater than guinea pigs greater than primates, leading to increasing "toxico-availability" in the reversed order.
Incubation of both sarin and soman with human plasma has shown that binding occurs to a tyrosine residue. Similar binding occurs when sarin and soman are incubated with human serum albumin. This binding may provide an important biological marker, which retains full structural information concerning the identity of the agent, in cases of allegations of chemical warfare use.
COMPOSITIONS AND METHODS FOR DETECTING NERVE AGENTS
申请人：Corcoran Robert C.
公开号：US20100130757A1
公开（公告）日：2010-05-27
The present invention provides methods and compositions for detecting, identifying and measuring the abundance of chemical nerve agents. Methods and compositions of the present invention are capable of providing selective detection of phosphorous based nerve agents, such as nerve agents that are esters of methyl phosphonic acid derivatives incorporating a moderately good leaving group at the phosphorus. Selectivity in the present invention is provided by a sensor composition having an alpha (α) effect nucleophile group that undergoes specific nucleophilic substitution and rearrangement reactions with phosphorus based nerve agents having a tetrahederal phosphorous bound to oxygen. The present invention includes embodiments employing a sensor composition further comprising a reporter group covalently linked to the alpha effect nucleophile group allowing rapid optical readout of nerve agent detection events, including direct visual readout and optical readout via spectroscopic analysis.
Visible-light C–heteroatom bond cleavage and detoxification of chemical warfare agents using titania-supported gold nanoparticles as photocatalyst
作者：Ştefan Neaţu、Bogdan Cojocaru、Vasile I. Pârvulescu、Vasile Şomoghi、Mercedes Alvaro、Hermenegildo Garcia
DOI：10.1039/c0jm00345j
日期：——
Gold nanoparticles supported on TiO2 effect the detoxification of soman and VX nerve gases and yperite vesicant agent at room temperature upon visible light illumination.
A dual-function all-inorganic intercluster salt comprising the polycation ε-[Al<sub>13</sub>O<sub>4</sub>(OH)<sub>24</sub>(H<sub>2</sub>O)<sub>12</sub>]<sup>7+</sup> and polyanion α-[PMo<sub>10</sub>V<sub>2</sub>O<sub>40</sub>]<sup>5−</sup> for detoxifying sulfur mustard and soman
作者：Jialin Yu、Qi Gao、Lijuan Zhang、Yunshan Zhou、Yuxu Zhong、Jianbo Yin、Yuanyuan Zhou、Fangsheng Tao、Yong'an Wang
DOI：10.1039/d0dt01307b
日期：——
The specially designed intercluster compound can catalytically decontaminate both HD and GD at ambient conditions with high efficiency.
这种特别设计的簇间化合物可以在常温下高效催化去污剂HD和GD。
COMPOUNDS AND METHODS TO TREAT ORGANOPHOSPHORUS POISONING
申请人：University of Iowa Research Foundation
公开号：US20140323473A1
公开（公告）日：2014-10-30
Organophosphate (OP) nerve agents and pesticides are potent inhibitors of acetylcholinesterase (AChE). Though oxime nucleophiles can reactivate an AChE-phosphyl adduct, the adduct can undergo a reaction called aging, leading to an aged-AChE adduct. The invention provides compounds and methods that can be used to reactivate an aged-AChE adduct. Such compounds and methods are useful to counteract organophosphorus poisoning.
CARBALDEHYDE OXIMES AS BUTYRYLCHOLINESTERASE REACTIVATORS
申请人：Etat Français représenté par la Direction Centrale
Du Service de Santé des Armées
公开号：EP3945092A1
公开（公告）日：2022-02-02
The present invention relates to compounds for their use in the reactivation of butyrylcholinesterase. Such compounds are useful in the treatment or prevention of the intoxication with at least one organophosphorus nerve agent. The invention also relates to pharmaceutical compositions and kits comprising said compounds, and compounds per se.
