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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).
In biochemistry, a cholinesterase or choline esterase is a family of esterases that lyses choline-based esters, several of which serve as neurotransmitters. Thus, it is either of two enzymes that catalyze the hydrolysis of these cholinergic neurotransmitters, such as breaking acetylcholine into choline and acetic acid. These reactions are necessary to allow a cholinergic neuron to return to its resting state after activation. For example, in muscle contraction, acetylcholine at a neuromuscular junction triggers a contraction; but for the muscle to relax afterward, rather than remaining locked in a tense state, the acetylcholine must be broken down by a choline esterase. The main type for that purpose is acetylcholinesterase ; it is found mainly in chemical synapses and red blood cell membranes. The other type is butyrylcholinesterase ; it is found mainly in the blood plasma.
Edrophonium is a readily reversible acetylcholinesterase inhibitor. It prevents breakdown of the neurotransmitter acetylcholine and acts by competitively inhibiting the enzyme acetylcholinesterase, mainly at the neuromuscular junction. It is sold under the trade names Tensilon and Enlon.
A parasympathomimetic drug, sometimes called a cholinomimetic drug or cholinergic receptor stimulating agent, is a substance that stimulates the parasympathetic nervous system (PSNS). These chemicals are also called cholinergic drugs because acetylcholine (ACh) is the neurotransmitter used by the PSNS. Chemicals in this family can act either directly by stimulating the nicotinic or muscarinic receptors, or indirectly by inhibiting cholinesterase, promoting acetylcholine release, or other mechanisms.
Pyridostigmine is a medication used to treat myasthenia gravis. It is also used together with atropine to end the effects of neuromuscular blocking medication of the non-depolarizing type. It is typically given by mouth but can also be used by injection. The effects generally begin within 45 minutes and last up to 6 hours.
Galantamine is used for the treatment of cognitive decline in mild to moderate Alzheimer's disease and various other memory impairments. It is an alkaloid that has been isolated from the bulbs and flowers of Galanthus nivalis, Galanthus caucasicus, Galanthus woronowii, and some other members of the family Amaryllidaceae, such as Narcissus (daffodil), Leucojum aestivum (snowflake), and Lycoris including Lycoris radiata. It can also be produced synthetically.
Obidoxime is a member of the oxime family used to treat nerve gas poisoning. Oximes are drugs known for their ability to reverse the binding of organophosphorus compounds to the enzyme acetylcholinesterase (AChE).
In biochemistry, suicide inhibition, also known as suicide inactivation or mechanism-based inhibition, is an irreversible form of enzyme inhibition that occurs when an enzyme binds a substrate analog and forms an irreversible complex with it through a covalent bond during the normal catalysis reaction. The inhibitor binds to the active site where it is modified by the enzyme to produce a reactive group that reacts irreversibly to form a stable inhibitor-enzyme complex. This usually uses a prosthetic group or a coenzyme, forming electrophilic alpha and beta unsaturated carbonyl compounds and imines.
Diisopropyl fluorophosphate (DFP) or Isoflurophate is an oily, colorless liquid with the chemical formula C6H14FO3P. It is used in medicine and as an organophosphorus insecticide. It is stable, but undergoes hydrolysis when subjected to moisture.
An enzyme inhibitor is a molecule that binds to an enzyme and decreases its activity. By binding to enzymes' active sites, inhibitors reduce the compatibility of substrate and enzyme and this leads to the inhibition of Enzyme-Substrate complexes' formation, preventing the catalysis of reactions and decreasing the amount of product produced by a reaction. It can be said that as the concentration of enzyme inhibitors increases, the rate of enzyme activity decreases, and thus, the amount of product produced is inversely proportional to the concentration of inhibitor molecules. Since blocking an enzyme's activity can kill a pathogen or correct a metabolic imbalance, many drugs are enzyme inhibitors. They are also used in pesticides. Not all molecules that bind to enzymes are inhibitors; enzyme activators bind to enzymes and increase their enzymatic activity, while enzyme substrates bind and are converted to products in the normal catalytic cycle of the enzyme.
Azinphos-methyl (Guthion) is a broad spectrum organophosphate insecticide manufactured by Bayer CropScience, Gowan Co., and Makhteshim Agan. Like other pesticides in this class, it owes its insecticidal properties to the fact that it is an acetylcholinesterase inhibitor. It is classified as an extremely hazardous substance in the United States as defined in Section 302 of the U.S. Emergency Planning and Community Right-to-Know Act, and is subject to strict reporting requirements by facilities which produce, store, or use it in significant quantities.
Ambenonium is a cholinesterase inhibitor used in the management of myasthenia gravis.
Acetylcholinesterase, also known as AChE or acetylhydrolase, is the primary cholinesterase in the body. It is an enzyme that catalyzes the breakdown of acetylcholine and of some other choline esters that function as neurotransmitters. AChE is found at mainly neuromuscular junctions and in chemical synapses of the cholinergic type, where its activity serves to terminate synaptic transmission. It belongs to carboxylesterase family of enzymes. It is the primary target of inhibition by organophosphorus compounds such as nerve agents and pesticides.
Chlorethoxyfos is an organophosphate acetylcholinesterase inhibitor used as an insecticide. It is registered for the control of corn rootworms, wireworms, cutworms, seed corn maggot, white grubs and symphylans on corn. The insecticide is sold under the trade name Fortress by E.I. du Pont de Nemours & Company.
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.
Ethoprophos (or ethoprop) is an organophosphate ester with the formula C8H19O2PS2. It is a clear yellow to colourless liquid that has a characteristic mercaptan-like odour. It is used as an insecticide and nematicide and it is an acetylcholinesterase inhibitor.
Methanesulfonyl fluoride (MSF) has long been known to be a potent inhibitor of acetylcholinesterase (AChE), the enzyme that regulates acetylcholine, an important neurotransmitter in both the central and peripheral nervous systems.
Terbufos is a chemical compound used in insecticides and nematicides. Terbufos is part of the chemical family of organophosphates. It is a clear, colourless to pale yellow or reddish-brown liquid and sold commercially as granulate.
IDFP is an organophosphorus compound related to the nerve agent sarin.
Chelidonine is an isolate of Papaveraceae with acetylcholinesterase and butyrylcholinesterase inhibitory activity.
References
- ↑ Millary, CB; Kryger, G (199). "Crystal structures of aged phosphorylated acetylcholinesterase: nerve agent reaction products at the atomic level". Biochemistry. Weizmann Institute of Science. 38 (22): 7032–7039. doi:10.1021/bi982678l. PMID 10353814.
- ↑ Julien, Robert (2008). A Primer of Drug Action (Eleventh ed.). Worth Publishers. p. 50. ISBN 978-1-4292-0679-2.