nerve agent nerve agent 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 acetylcholinesterase inhibitors used as poison. part of a series onchemical agents lethal agents blood cyanogen chloride (ck) hydrogen cyanide (ac) arsine (sa) blister ethyldichloroarsine (ed) methyldichloroarsine (md) phenyldichloroarsine (pd) lewisite (l) mustard gas(hd h ht hl hq) nitrogen mustardhn1hn2hn3 nerve g-agents tabun (ga) sarin (gb) chlorosarin (gc) soman (gd) ethylsarin (ge) cyclosarin (gf) gv v-agents ea-3148 v-sub x/gd-7, ve vg vm vp vr vs vx novichok agents a-230 a-232 a-234 a-242 a-262 c01-a035 c01-a039 c01-a042 nettle phosgene oxime (cx) c01-a035 c01-a039 pulmonary/choking chlorine chloropicrin (ps) phosgene (cg) diphosgene (dp) disulfur decafluoride vomiting adamsite chloropicrin diphenylchlorarsine diphenylcyanoarsine diphenylamincyanoarsine incapacitating agents agent 15 (bz) dimethylheptylpyran (dmhp) ea-3167 kolokol-1 pava spray sleeping gas riot-control (rcas) xylyl bromide pepper spray (oc) cs cn (mace) cr list of chemical warfare agents poisoning by a nerve agent leads to constriction 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, 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. biological effects nerve agents attack the nervous system. all such agents function the same way resulting in cholinergic crisis: they inhibit the enzyme acetylcholinesterase, which is responsible for the breakdown of acetylcholine (ach) in the synapses between nerves that control whether muscle tissues are to relax or contract. if the agent cannot be broken down, muscles are prevented from receiving 'relax' signals and they are effectively paralyzed.: 131–139 it is the compounding of this paralysis throughout the body that quickly leads to more severe complications, including the heart and the muscles used for breathing. because of this, the first symptoms usually appear within 30 seconds of exposure and death can occur via asphyxiation or cardiac arrest in a few minutes, depending upon the dose received and the agent used. 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. 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.: 147–149 the effects of nerve agents are long lasting and increase with continued exposure. survivors of nerve agent poisoning almost invariably develop chronic neurological damage and related psychiatric effects. 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. 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 reaction product of the most important nerve agents, including soman, sarin, tabun and vx, with acetylcholinesterase were solved by the u.s. army using x-ray crystallography in the 1990s. the reaction products have been confirmed subsequently using different sources of acetylcholinesterase and the closely related target enzyme, butyrylcholinesterase. the x-ray structures clarify important aspects of the reaction mechanism (e.g., stereochemical inversion) at atomic resolution and provide a key tool for antidote development. treatment standard treatment for nerve agent poisoning is a combination of an anticholinergic to manage the symptoms, and an oxime as an antidote. anticholinergics treat the symptoms by reducing the effects of acetylcholine, while oximes displaces phosphate molecules from the active site of the cholinesterase enzymes, allowing the breakdown of acetylcholine. military personnel are issued the combination in an autoinjector (e.g. atnaa), for ease of use in stressful conditions. atropine is the standard anticholinergic drug used to manage the symptoms of nerve agent poisoning. it acts as an antagonist to muscarinic acetylcholine receptors, blocking the effects of excess acetylcholine. some synthetic anticholinergics, such as biperiden, may counteract the central symptoms of nerve agent poisoning more effectively 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. pralidoxime chloride (also known as 2-pamcl) is the standard oxime used to treat nerve agent poisoning. 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, counteracting the nerve agent itself. revival of acetylcholinesterase with pralidoxime chloride works more effectively on nicotinic receptors while blocking acetylcholine receptors with atropine is more effective on muscarinic receptors. anticonvulsants, such as diazepam, may be administered to manage seizures, improving long term prognosis and reducing risk of brain damage. this is not usually self-administered as its use is for actively seizing patients. countermeasures pyridostigmine bromide was used by the us military in the first gulf war as a pretreatment for soman as it increased the median lethal dose. it is only effective if taken prior to exposure and in conjunction with atropine and pralidoxime, issued in the mark i naak autoinjector, and is ineffective against other nerve agents. while it reduces fatality rates, there is an increased risk of brain damage; this can be mitigated by administration of an anticonvulsant. evidence suggests that the use of pyridostigmine may be responsible for some of the symptoms of gulf war syndrome. butyrylcholinesterase is under development by the u.s. department of defense as a prophylactic countermeasure against organophosphate nerve agents. it binds nerve agent in the bloodstream before the poison can exert effects in the nervous system. both purified acetylcholinesterase and butyrylcholinesterase have demonstrated success in animal studies as "biological scavengers" (and universal targets) to provide stoichiometric protection against the entire spectrum of organophosphate nerve agents. butyrylcholinesterase currently is the preferred enzyme for development as a pharmaceutical drug primarily because it is a naturally circulating human plasma protein (superior pharmacokinetics) and its larger active site compared with acetylcholinesterase may permit greater flexibility for future design and improvement of butyrylcholinesterase to act as a nerve agent scavenger. classes there are two main classes of nerve agents. the members of the two classes share similar properties and are given both a common name (such as sarin) and a two-character nato identifier (such as gb). g-series chemical form of the nerve agent tabun, the first ever synthesized. the g series of nerve agents. the g-series is thus named because german scientists first synthesized them. g series agents are known as non-persistent, meaning that they evaporate shortly after release, and do not remain active in the dispersal area for very long. all of the compounds in this class were discovered and synthesized during or prior to world war ii, led by gerhard schrader (later under the employment of ig farben). this series is the first and oldest family of nerve agents. the first nerve agent ever synthesized was ga (tabun) in 1936. gb (sarin) was discovered next in 1939, followed by gd (soman) in 1944, and finally the more obscure gf (cyclosarin) in 1949. gb was the only g agent that was fielded by the us as a munition, in rockets, aerial bombs, and artillery shells. v-series chemical form of the nerve agent vx. the v series of nerve agents. the v-series is the second family of nerve agents and contains five well known members: ve, vg, vm, vr, and vx, along with several more obscure analogues. the most studied agent in this family, vx (it is thought that the 'x' in its name comes from its overlapping isopropyl radicals), was invented in the 1950s at porton down in the united kingdom. ranajit ghosh, a chemist at the plant protection laboratories of imperial chemical industries (ici) was investigating a class of organophosphate compounds (organophosphate esters of substituted aminoethanethiols). like schrader, ghosh found that they were quite effective pesticides. in 1954, ici put one of them on the market under the trade name amiton. it was subsequently withdrawn, as it was too toxic for safe use. the toxicity did not escape military notice and some of the more toxic materials had been sent to the british armed forces research facility at porton down for evaluation. after the evaluation was complete, several members of this class of compounds became a new group of nerve agents, the v agents (depending on the source, the v stands for victory, venomous, or viscous). the best known of these is probably vx, with vr ("russian v-gas") coming a close second (amiton is largely forgotten as vg, with g probably coming from "g"hosh). all of the v-agents are persistent agents, meaning that these agents do not degrade or wash away easily and can therefore remain on clothes and other surfaces for long periods. in use, this allows the v-agents to be used to blanket terrain to guide or curtail the movement of enemy ground forces. the consistency of these agents is similar to oil; as a result, the contact hazard for v-agents is primarily – but not exclusively – dermal. vx was the only v-series agent that was fielded by the us as a munition, in rockets, artillery shells, airplane spray tanks, and landmines. analyzing the structure of thirteen v agents, the standard composition, which makes a compound enter this group, is the absence of halides. it is clear that many agricultural pesticides can be considered as v agents if they are notoriously toxic. the agent is not required to be a phosphonate and presents a dialkylaminoethyl group. the toxicity requirement is waived as the vt agent and its salts (vt-1 and vt-2) are "non-toxic". replacing the sulfur atom with selenium increases the toxicity of the agent by orders of magnitude. novichok agents main article: novichok agent the novichok (russian: новичо́к, "newcomer") agents, a series of organophosphate compounds, were developed in the soviet union and in russia from the mid-1960s to the 1990s. the novichok program aimed to develop and manufacture highly deadly chemical weapons that were unknown to the west. the new agents were designed to be undetectable by standard nato chemical-detection equipment and overcome contemporary chemical-protective equipment. in addition to the newly developed "third generation" weapons, binary versions of several soviet agents were developed and were designated as "novichok" agents. carbamates contrary to some claims, not all nerve agents are organophosphates. the starting compound studied by the usa was the carbamate ea-1464, of notorious