Nerve agent

Nerve agents 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, an enzyme that catalyzes the breakdown of acetylcholine, a neurotransmitter.

Poisoning by a nerve agent leads to contraction of pupils, profuse salivation, convulsions, and involuntary urination and defecation, with the first symptoms appearing in seconds after exposure. Death by asphyxiation or cardiac arrest may follow in minutes due to the loss of the body's control over respiratory and other muscles. Some nerve agents are readily vaporized or aerosolized, and the primary portal of entry into the body is the respiratory system. Nerve agents can also be absorbed through the skin, requiring that those likely to be subjected to such agents wear a full body suit in addition to a respirator.

Nerve agents are generally colorless to amber-colored, tasteless liquids that may evaporate to a gas. Agents sarin and VX are odorless; tabun has a slightly fruity odor and soman has a slight camphor odor. [1]

Biological effects

Nerve agents attack the nervous system of the human body. All such agents function the same way: by inhibiting the enzyme acetylcholinesterase, which is responsible for the breakdown of acetylcholine (ACh) in the synapse. ACh gives the signal for muscles to contract. Thus, if it cannot be broken down, muscles are prevented from relaxing and they are effectively paralyzed. [2]:131–139 This includes the heart and the muscles used for breathing. Because of this, the first symptoms usually appear within seconds of exposure and death can occur via asphyxiation or cardiac arrest in a few minutes. [1]

Initial symptoms following exposure to nerve agents (like sarin) are a runny nose, tightness in the chest, and constriction of the pupils. Soon after, the victim will have difficulty breathing and will experience nausea and salivation. As the victim continues to lose control of bodily functions, involuntary salivation, lacrimation, urination, defecation, gastrointestinal pain and vomiting will be experienced. Blisters and burning of the eyes and/or lungs may also occur. [3] [4] This phase is followed by initially myoclonic jerks (muscle jerks) followed by status epilepticus -type epileptic seizure. Death then comes via complete respiratory depression, most likely via the excessive peripheral activity at the neuromuscular junction of the diaphragm. [2]:147–149

The effects of nerve agents are long lasting and increase with continued exposure. Survivors of nerve agent poisoning almost invariably suffer chronic neurological damage and related psychiatric effects. [5] Possible effects that can last at least up to 2–3 years after exposure include blurred vision, tiredness, declined memory, hoarse voice, palpitations, sleeplessness, shoulder stiffness and eye strain. In people exposed to nerve agents, serum and erythrocyte acetylcholinesterase in the long-term are noticeably lower than normal and tend to be lower the worse the persisting symptoms are. [6] [7]

Mechanism of action

When a normally functioning motor nerve is stimulated, it releases the neurotransmitter acetylcholine, which transmits the impulse to a muscle or organ. Once the impulse is sent, the enzyme acetylcholinesterase immediately breaks down the acetylcholine in order to allow the muscle or organ to relax.

Nerve agents disrupt the nervous system by inhibiting the function of the enzyme acetylcholinesterase by forming a covalent bond with its active site, where acetylcholine would normally be broken down (undergo hydrolysis). Acetylcholine thus builds up and continues to act so that any nerve impulses are continually transmitted and muscle contractions do not stop. This same action also occurs at the gland and organ levels, resulting in uncontrolled drooling, tearing of the eyes (lacrimation) and excess production of mucus from the nose (rhinorrhea).

The structures of the complexes of soman (one of the most toxic nerve agents) with acetylcholinesterase from Torpedo californica have been solved by X-ray crystallography (PDB codes: 2wfz, [8] 2wg0, [9] 2wg1, [10] and 1som). [11] The mechanism of action of soman could be seen on example of 2wfz. [8]


Atropine and related anticholinergic drugs act as antidotes to nerve agent poisoning because they block acetylcholine receptors, but they are poisonous in their own right. [12] Some synthetic anticholinergics, such as biperiden, [13] may counteract the central symptoms of nerve agent poisoning better than atropine, since they pass the blood–brain barrier better than atropine.[ citation needed] While these drugs will save the life of a person affected by nerve agents, that person may be incapacitated briefly or for an extended period, depending on the extent of exposure. The endpoint of atropine administration is the clearing of bronchial secretions. Atropine for field use by military personnel is often loaded in an autoinjector (e.g. ATNAA), for ease of use in stressful conditions. [12]

Pralidoxime chloride, also known as 2-PAM chloride, is also used as an antidote. [12] Rather than counteracting the initial effects of the nerve agent on the nervous system as does atropine, pralidoxime chloride reactivates the poisoned enzyme (acetylcholinesterase) by scavenging the phosphoryl group attached on the functional hydroxyl group of the enzyme. [14] Though safer to use than atropine, it takes longer to act.

Revival of acetylcholinesterase with pralidoxime chloride works more effectively on nicotinic receptors while blocking acetylcholine receptors with atropine is more effective on muscarinic receptors. Often, severe cases of poisoning are treated with both drugs. [12]

Countermeasures in development

Butyrylcholinesterase is a prophylactic countermeasure against organophosphate nerve agents. It binds nerve agent in the bloodstream before it can exert effects in the nervous system. Because it is a biological scavenger (and universal target), it is currently the only therapeutic agent effective in providing complete stoichiometric protection against the entire spectrum of organophosphate nerve agents. [15]

Other Languages
español: Gas nervioso
Esperanto: Nerva gaso
français: Agent innervant
Gaeilge: Néarghás
italiano: Gas nervino
עברית: גז עצבים
македонски: Нервен гас
Bahasa Melayu: Agen saraf
Nederlands: Zenuwgas
日本語: 神経ガス
norsk: Nervegass
português: Agente nervoso
română: Gaz iritant
Simple English: Nerve agent
slovenščina: Živčni strup
српски / srpski: Nervni agens
suomi: Hermokaasu
svenska: Stridsgas
Türkçe: Sinir gazı