Cholinesterase reactivator

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Cholinesterase reactivators are drugs that reverse the inhibition of cholinesterase by organophosphates or sulfonates. [1] They are used as antidote for treating organophosphate insecticide and nerve agent poisoning. [2]

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Nerve agents, sometimes also called nerve gases, are a class of organic chemicals that disrupt the mechanisms by which nerves transfer messages to organs. The disruption is caused by the blocking of acetylcholinesterase (AChE), an enzyme that catalyzes the breakdown of acetylcholine, a neurotransmitter. Nerve agents are irreversible acetylcholinesterase inhibitors used as poison.

<span class="mw-page-title-main">Soman</span> Chemical compound (nerve agent)

Soman is an extremely toxic chemical substance. It is a nerve agent, interfering with normal functioning of the mammalian nervous system by inhibiting the enzyme cholinesterase. It is an inhibitor of both acetylcholinesterase and butyrylcholinesterase. As a chemical weapon, it is classified as a weapon of mass destruction by the United Nations according to UN Resolution 687. Its production is strictly controlled, and stockpiling is outlawed by the Chemical Weapons Convention of 1993 where it is classified as a Schedule 1 substance. Soman was the third of the so-called G-series nerve agents to be discovered along with GA (tabun), GB (sarin), and GF (cyclosarin).

<span class="mw-page-title-main">VX (nerve agent)</span> Chemical compound and chemical warfare nerve agent

VX is an extremely toxic synthetic chemical compound in the organophosphorus class, specifically, a thiophosphonate. In the class of nerve agents, it was developed for military use in chemical warfare after translation of earlier discoveries of organophosphate toxicity in pesticide research. In its pure form, VX is an oily, relatively non-volatile liquid that is amber-like in colour. Because of its low volatility, VX persists in environments where it is dispersed.

<span class="mw-page-title-main">Cholinesterase</span> Esterase that lyses choline-based esters

The enzyme cholinesterase (EC 3.1.1.8, choline esterase; systematic name acylcholine acylhydrolase) catalyses the hydrolysis of choline-based esters:

<span class="mw-page-title-main">Chlorfenvinphos</span> Chemical compound

Chlorfenvinphos is an organophosphorus compound that was widely used as an insecticide and an acaricide. The molecule itself can be described as an enol ester derived from dichloroacetophenone and diethylphosphonic acid. Chlorfenvinphos has been included in many products since its first use in 1963. However, because of its toxic effect as a cholinesterase inhibitor it has been banned in several countries, including the United States and the European Union. Its use in the United States was discontinued in 1991.

<span class="mw-page-title-main">VG (nerve agent)</span> Chemical compound

VG is a "V-series" nerve agent chemically similar to the better-known VX nerve agent. Tetram is the common Russian name for the substance. Amiton was the trade name for the substance when it was marketed as an insecticide by ICI in the mid-1950s.

Obidoxime is a member of the oxime family used to treat organophosphate poisoning. Oximes are drugs known for their ability to reverse the binding of organophosphorus compounds to the enzyme acetylcholinesterase (AChE).

Novichok is a family of nerve agents, some of which are binary chemical weapons. The agents were developed at the GosNIIOKhT state chemical research institute by the Soviet Union and Russia between 1971 and 1993. Some Novichok agents are solids at standard temperature and pressure, while others are liquids. Dispersal of solid form agents is thought possible if in ultrafine powder state.

A cholinergic crisis is an over-stimulation at a neuromuscular junction due to an excess of acetylcholine (ACh), as a result of the inactivity of the AChE enzyme, which normally breaks down acetylcholine.

<span class="mw-page-title-main">Pralidoxime</span> Chemical compound as an antidote

Pralidoxime or 2-PAM, usually as the chloride or iodide salts, belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase. It is used to treat organophosphate poisoning in conjunction with atropine and either diazepam or midazolam. It is a white solid.

<span class="mw-page-title-main">Dioxathion</span> Chemical compound

Dioxathion, systematically known as p-dioxane-2,3-diyl ethyl phosphorodithioate, is an organophosphate pesticide. It is used as an insecticide on livestock and as an acaricide on citrus fruits, deciduous fruits and nuts.

<span class="mw-page-title-main">Organophosphate poisoning</span> Toxic effect of pesticides

Organophosphate poisoning is poisoning due to organophosphates (OPs). Organophosphates are used as insecticides, medications, and nerve agents. Symptoms include increased saliva and tear production, diarrhea, vomiting, small pupils, sweating, muscle tremors, and confusion. While onset of symptoms is often within minutes to hours, some symptoms can take weeks to appear. Symptoms can last for days to weeks.

<span class="mw-page-title-main">Paraoxon</span> Chemical compound

Paraoxon is a parasympathomimetic drug which acts as an cholinesterase inhibitor. It is an organophosphate oxon, and the active metabolite of the insecticide parathion. It is also used as an ophthalmological drug against glaucoma. Paraoxon is one of the most potent acetylcholinesterase-inhibiting insecticides available, around 70% as potent as the nerve agent sarin, and so is now rarely used as an insecticide due to the risk of poisoning to humans and other animals. Paraoxon has been used by scientists to study acute and chronic effects of organophosphate intoxication. It is easily absorbed through skin, and was allegedly used as an assassination weapon by the apartheid-era South African chemical weapons program Project Coast.

An ATNAA is any of a variety of autoinjectors in use with the US Armed Forces. An autoinjector is a medical device designed to deliver a single dose of a particular drug.

<span class="mw-page-title-main">Acetylcholinesterase inhibitor</span> Drugs that inhibit acetylcholinesterase

Acetylcholinesterase inhibitors (AChEIs) also often called cholinesterase inhibitors, inhibit the enzyme acetylcholinesterase from breaking down the neurotransmitter acetylcholine into choline and acetate, thereby increasing both the level and duration of action of acetylcholine in the central nervous system, autonomic ganglia and neuromuscular junctions, which are rich in acetylcholine receptors. Acetylcholinesterase inhibitors are one of two types of cholinesterase inhibitors; the other being butyryl-cholinesterase inhibitors. Acetylcholinesterase is the primary member of the cholinesterase enzyme family.

<span class="mw-page-title-main">Demeton</span> Chemical compound

Demeton, sold as an amber oily liquid with a sulphur like odour under the name Systox, is an organophosphate derivative causing irritability and shortness of breath to individuals repeatedly exposed. It was used as a phosphorothioate insecticide and acaricide and has the chemical formula C8H19O3PS2. Although it was previously used as an insecticide, it is now largely obsolete due to its relatively high toxicity to humans. Demeton consists of two components, demeton-S and demeton-O in a ratio of approximately 2:1 respectively. The chemical structure of demeton is closely related to military nerve agents such as VX and a derivative with one of the ethoxy groups replaced by methyl was investigated by both the US and Soviet chemical-weapons programs under the names V-sub x and GD-7.

V-sub x, also known as GD-7, is an organophosphate nerve agent of the V-series, the phosphonate analog of the organophosphate insecticide demeton. EA-5478 is the pinacolyl analogue.

<span class="mw-page-title-main">Crotylsarin</span> Chemical compound

Crotylsarin (CRS) is an extremely toxic organophosphate nerve agent of the G-series. Like other nerve agents, CRS irreversibly inhibits acetylcholinesterase. However, since the inhibited enzyme ages so rapidly, it can't be reactivated by cholinesterase reactivators.

<span class="mw-page-title-main">Methylfluorophosphonylcholine</span> Chemical compound

Methylfluorophosphonylcholine (MFPCh) is an extremely toxic chemical compound related to the G-series nerve agents. It is an extremely potent acetylcholinesterase inhibitor which is around 100 times more potent than sarin at inhibiting acetylcholinesterase in vitro, and around 10 times more potent in vivo, depending on route of administration and animal species tested. MFPCh is resistant to oxime reactivators, meaning the acetylcholinesterase inhibited by MFPCh can't be reactivated by cholinesterase reactivators. MFPCh also acts directly on the acetylcholine receptors. MFPCh is a relatively unstable compound and degrades rapidly in storage, so despite its enhanced toxicity it was not deemed suitable to be weaponised for military use.

<span class="mw-page-title-main">Selenophos</span> Chemical compound

Selenophos is an extremely potent organophosphate acetylcholinesterase inhibitor. It is the selenium analog of the VE nerve agent.

References

  1. "Cholinesterase Reactivators - MeSH - NCBI". www.ncbi.nlm.nih.gov.
  2. Antonijevic, B.; Stojiljkovic, M. P. (1 March 2007). "Unequal Efficacy of Pyridinium Oximes in Acute Organophosphate Poisoning". Clinical Medicine & Research. 5 (1): 71–82. doi:10.3121/cmr.2007.701. PMC   1855336 . PMID   17456837.