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

Updated: Jan 05, 2016
  • Author: Kermit D Huebner, MD, FACEP; Chief Editor: Duane C Caneva, MD, MSc  more...
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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. GB was discovered next in 1938, followed by GD in 1944 and finally the more obscure GF in 1949. The only other known nerve agent, O-ethyl S-(2-diisopropylaminoethyl) methylphosphonothioate (VX), is 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 and GD smell fruity.

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.

Accordingly, the lethality of these agents varies with the route of exposure. For inhalational exposures to GB, the lethal concentration time product in 50% of the exposed population is 75-100 mg·min/m3. For dermal exposures, the lethal dose in 50% of the exposed population is 1700 mg.



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. [3] 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. [4, 5]

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). [6] 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. [4]

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. [7] 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. [8]

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.




United States

Nerve agent exposure is extremely rare in the US.


Despite international attempts to control the proliferation of chemical weapons, nerve agents reportedly still are stockpiled by the militaries of several countries.

To date, no large-scale military deployment of a nerve agent has occurred during war, although indirect evidence exists that the Iraqi military used GB against Kurdish villagers in 1988 as well as during the Iraq-Iran War. [9]

In 1994, the Japanese terrorist cult, Aum Shinrikyo, synthesized and then deployed GB against civilians at Matsumoto, Japan, killing 8 people. [10] 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. [11]