How do nerve agents work on a biological level?

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I was reading about the [Novichok agent](https://www.reddit.com/r/wallstreetbets/comments/kbyxet/a_little_wordplay/?utm_source=share&utm_medium=web2x&context=3) and I’d like to know more about how it works along with other nerve agents without the complicated science jargon.

In: Biology

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Anonymous 0 Comments

Novichok agents belong to a class of compounds called Organophosphates. In general these contain a phosphorous atom bound to at least one carbon atom and generally 2 oxygen atoms.

Nerve agents are usually classified as being toxins that act on the neurotransmitter acetylcholine. (This includes those in organophosphate class and some other chemistries.)

Acetylcholine is the chief neurotransmitter the motor nerves use to activate muscles. Motor nerves release acetylcholine which binds to gated ion channel proteins in muscles which releases calcium ions. This triggers muscles to contract.

By disrupting the acetylcholine system, these cause difficulty with muscle control, spasms paralysis, particularly breathing muscles, and life threatening heart arrhythmia.

When the nerves stop firing, leftover acetylcholine is broken down and cleared from the junction between nerves and muscles by a group of enzymes called Cholinesterases. These are some of the most rapid acting enzymes known in the body, one of these enzymes can potentially break down several hundred acetylcholine molecules per second.

Novichok agents, along with most nerve agents, can cause a permanent structural change to the folding of the Cholinesterase enzyme, which irreversibly inhibits it. This means it stops it from being able to bind with acetylcholine. One molecule of a Novichok or other nerve agent can deactivate many Cholinesterase proteins. Potentially thousands. This explains their extreme toxicity.

This causes acetylcholine to build up in the the junction and eventually build up in the bloodstream in general, causing muscles to act abnormally. Eventually muscles stop being able to respond to nerve signals completely, resulting in paralysis and many other symptoms.

Aside from chemical weapons, a number of insecticides belong to the organophosphate class. Cholinesterases in insects have a significantly different structure than in vertebrates. Such insecticides have a different chemistry and are far, far more toxic to insects than to vertebrates. But they are still somewhat toxic, and can cause symptoms of nerve agent poisoning in large exposures on humans.

Some of the first chemical weapons were originally developed as pesticides or rodenticides. In the 1800, one of the first pesticides developed was phosphine gas (PH4.) This acts in the same way by irreversibly deactivating Cholinesterase. It was used as a fumigant to kill rodents and insects Luke bedbugs. Because it is is rapidly oxidized in air into phosphoric acid in a matter of an hour or two, its still used sometimes in the present day. Windows and vents in a building are sealed and the phosphine is generated with a chemical reaction. Once the reaction is finished, the phosphine breaks down in air and the building is safe to enter after a few hours.

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