CBRNE - Nerve Agents, G-series - Tabun, Sarin, Soman

Updated: Oct 02, 2021
  • Author: Kermit D Huebner, MD, FACEP; Chief Editor: Duane C Caneva, MD, MSc  more...
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Practice Essentials

The organophosphate nerve agents tabun (GA), sarin (GB), soman (GD), and cyclosarin (GF) are among the most toxic chemical warfare agents known. [1, 2]  Together they comprise the G-series nerve agents, thus named because German scientists first synthesized them, beginning with GA in 1936. The more highly toxic V-series agents ("V" stands for venomous)—principally, O-ethyl S-(2-diisopropylaminoethyl) methylphosphonothioate (VX)—are discussed in a separate Medscape article (see CBRNE - Nerve Agents, V-series - Ve, Vg, Vm, Vx).

G-series nerve agents share a number of common physical and chemical properties. At room temperature, the G-series nerve agents are volatile liquids, making them a serious risk for exposure from dermal contact with liquid nerve agent or inhalation of nerve agent vapor. GB is the most volatile of these agents and evaporates at the same rate as water; GD is the next most volatile. Dispersal devices or an explosive blast also can aerosolize nerve agents. Nerve agent vapors are denser than air, making them particularly hazardous for persons in low areas or underground shelters. GB and GD are colorless, while GA ranges from colorless to brown. GB is odorless, while GA has a slightly fruity odor and GD has a slight camphor-like odor.

Nerve agent exposure may occur as a result of any of the following [3] :

  • Industrial accident involving nerve agent production
  • Accidental release from a military stockpile
  • Chemical warfare
  • Chemical terrorism

Because nerve agents are soluble in fat and water, they are absorbed readily through the eyes, respiratory tract, and skin. Vapor agents penetrate the eyes first, producing localized effects, then pass into the respiratory tract, with more generalized effects when the exposure is greater. Liquid agents penetrate the skin at the point of contact, producing localized effects followed by deeper penetration and generalized effects if the dose is large enough. Vapors are not absorbed through the skin except at very high concentrations. Ocular effects may result from both direct contact and systemic absorption.

Accordingly, the lethality of these agents varies with the route of exposure. The lethal concentration-time product in 50% of the exposed population is 400 mg-min/m3 for GA. For dermal exposures, 1 to 10 mL of GA, GB, or GD can be fatal. [4]




Nerve agents act by first binding and then irreversibly inactivating acetylcholinesterase (AChE), producing a toxic accumulation of acetylcholine (ACh) at muscarinic, nicotinic, and CNS synapses. [5] Excessive ACh at these cholinergic receptors may account for the spectrum of clinical effects observed in nerve agent exposure.

At muscarinic receptors, nerve agents cause miosis, glandular hypersecretion (salivary, bronchial, lacrimal), bronchoconstriction, vomiting, diarrhea, urinary and fecal incontinence, and bradycardia. At nicotinic receptors in skin, nerve agents cause sweating, and on skeletal muscle, they cause initial defasciculation followed by weakness and flaccid paralysis. At CNS cholinergic receptors, nerve agents produce irritability, giddiness, fatigue, lethargy, amnesia, ataxia, seizures, coma, and respiratory depression. [6, 7]

Nerve agents also cause tachycardia and hypertension via stimulation of the adrenal medulla. They also appear to bind nicotinic, cardiac muscarinic, and glutamate N -methyl-d-aspartate (NMDA) receptors directly, suggesting that they may have additional mechanisms of action yet to be defined. Nerve agents also antagonize gamma-aminobutyric acid (GABA) neurotransmission, which in part may mediate seizures and CNS neuropathology.

Clinical effects of nerve agents depend on the route and amount of exposure. The effect of inhalational exposure to nerve agent vapor in turn depends on the vapor concentration and the time of exposure. Exposure to low concentrations of nerve agent vapor produces immediate ocular symptoms, rhinorrhea, and in some patients, dyspnea. These ocular effects are secondary to the localized absorption of GB vapor across the outermost layers of the eye, causing lacrimal gland stimulation (tearing), pupillary sphincter contraction (miosis), and ciliary body spasm (ocular pain). [8] As the exposure increases, dyspnea and gastrointestinal symptoms ensue.

Exposure to high concentrations of nerve agent vapor causes immediate loss of consciousness, followed shortly by convulsions, flaccid paralysis, and respiratory failure. These generalized effects are caused by the rapid absorption of nerve agent vapor across the respiratory tract, producing maximal inhibition of AChE within seconds to minutes of exposure. Nerve agent vapor is expected to have had its full effect by the time victims present to the emergency care system. [6]

The effect of dermal exposure to liquid nerve agent depends on the anatomic site exposed, ambient temperature, and dose of nerve agent. Percutaneous absorption of nerve agent typically results in localized sweating caused by direct nicotinic effect on the skin, followed by muscular fasciculations and weakness as the agent penetrates deeper and a nicotinic effect is exerted on underlying muscle. In moderate dermal exposures, vomiting and/or diarrhea occur. Vomiting and/or diarrhea soon after exposure are ominous signs. With further absorption, full-blown systemic or remote effects occur.

Because percutaneous absorption takes time, the onset of symptoms in dermal exposures usually is delayed. Even with thorough decontamination, symptoms may not occur until several hours have elapsed if some agent was absorbed prior to decontamination. A small droplet of GB liquid on the skin may not produce any clinical effects for as long as 18 hours postexposure. A large droplet of GB liquid rapidly causes loss of consciousness, seizures, paralysis, and apnea but only after a brief asymptomatic period typically lasting 10-30 minutes.

Miosis cannot be used as a marker for the severity of nerve agent exposure, because it depends on the route and time course of exposure. In inhalational exposures, miosis occurs early and frequently. In such exposures, normal pupil size is predictive of nontoxicity. [9] However, in dermal exposures at sites distinct from the eye, miosis occurs later in the progression of toxicity and depends on whether significant systemic absorption has occurred.

Nerve agents cause death via respiratory failure, which in turn is caused by increased airway resistance (bronchorrhea, bronchoconstriction), respiratory muscle paralysis, and most importantly, loss of central respiratory drive. [10]

Two chemical properties of nerve agents also provide the rationale for effective measures against them. First, nerve agents are hydrolyzed readily by alkaline solutions, which explains why soap and water or hypochlorite solutions are effective skin decontaminants. Second, the bond between the nerve agent and AChE takes time to chemically mature and become a stable covalent bond. During the period immediately after nerve agent binding to enzyme, the bond is vulnerable to disruption by agents called oximes. This aging phenomenon forms the pharmacologic basis for the effective use of the antidote, pralidoxime, during this early window of opportunity before the bond becomes permanent.



Nerve agent exposure is extremely rare in the United States. Despite international attempts to control the proliferation of chemical weapons, nerve agents reportedly still are stockpiled by the militaries of several countries.

Sarin gas has been documented as the chemical wapon used in the attacks by the Syrian goverment on Eastern Ghouta and Aleppo in 2013, and Khan Sheikhoun in 2017, [11]  resulting in over 1500 fatalities. [12]

In 1994, the Japanese terrorist cult, Aum Shinrikyo, synthesized and then deployed GB against civilians at Matsumoto, Japan, killing 8 people. [13]  The following year, the same terrorist group released GB again in the infamous Tokyo Subway sarin attack, killing 13 and sending 5500 persons to local hospitals. [14]

Indirect evidence exists that the Iraqi military used GB against Kurdish villagers in 1988 as well as during the Iraq-Iran War. [15]  In 2004, Iraqi insurgents exploded a device improvised from an artillery shell that contained degraded sarin. The attack failed to inflict casualties, but two U.S. service members were treated for minor symptoms usually associated with the agent. [16]  





Incapacitating effects and fatal effects can occur within 1 to 10 minutes for GA, GB, and GD. [4]  CNS effects such as fatigue, irritability, nervousness and impairment of memory may persist for as long as 6 weeks after recovery from acute effects. [17]   

After a severe exposure with prolonged seizures, permanent damage to the central nervous system is possible. [4]   Few data are available describing long-term effects of nerve agent exposure.  Structural brain damage in animals has been attributed to nerve agent–induced seizures. A consensus panel of experts concluded that structural brain damage does not occur until seizures have lasted longer than 45 minutes. [18]

A study by Chao et al examined long-term effects of sarin exposure on brain function in 40 soldiers with suspected exposure. [19]   No long-term cognitive effects were noted.

Miosis-related visual problems in dim light and mental lapses have been reported as long as 6-8 months after nerve agent exposure.

In long-term studies of victims of the Tokyo subway GB attack, postural imbalance has been reported 8 months after exposure to GB. [20] Fatigue, asthenia, nausea, shoulder stiffness, and blurred vision have been reported 3 years after exposure to GB. [21]


Patient Education

Counsel patients who are discharged home with miosis to avoid driving at night. For patient education information, see the First Aid and Injuries Center, as well as Chemical Warfare and Personal Protective Equipment