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.
: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
cardiac arrest in a few minutes.
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
gastrointestinal pain and
vomiting will be experienced.
Blisters and burning of the eyes and/or lungs may also occur.
 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
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
 Possible effects that can last at least up to 2–3 years after exposure include blurred vision,
tiredness, declined memory, hoarse voice,
sleeplessness, shoulder stiffness and
eye strain. In people exposed to nerve agents,
erythrocyte acetylcholinesterase in the long-term are noticeably lower than normal and tend to be lower the worse the persisting symptoms are.
Mechanism of action
When a normally functioning
motor nerve is stimulated, it releases the
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
Torpedo californica have been solved by X-ray crystallography (PDB codes: 2wfz,
 and 1som).
 The mechanism of action of soman could be seen on example of 2wfz.
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.
 Some synthetic anticholinergics, such as
 may counteract the central symptoms of nerve agent poisoning better than atropine, since they pass the
blood–brain barrier better than atropine. 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
ATNAA), for ease of use in stressful conditions.
Pralidoxime chloride, also known as 2-PAM chloride, is also used as an antidote.
 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.
 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.
Countermeasures in development
Butyrylcholinesterase is a
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.