Some of the most potent organophosphate nerve agents known are within a family of compounds known as the V-series, and the most well-known compound of this series is known as VX. VX was first synthesized in the early 1950s in the United Kingdom by Dr. Ranajit Ghosh, who was working for Imperial Chemical Industries to look for a new class of pesticides. The chemical name for VX is O-ethyl S-[2(diisopropylamino)ethyl] methylphosphonothioate (quite a mouthful!). Another common agent in this series is known as Russian VX (RVX), which is very similar in term of molecular structure to VX but has a few minor differences, making it roughly half as toxic as VX. 

Molecular structures of VX (top), RVX (middle), and acetylcholine (bottom). 

    VX compounds can be found in either liquid or solid form. VX liquid appears clear or brownish, is odorless, and has an oily consistency. This can make it hard to tell whether or not a person has been exposed to VX until the onset of symptoms. VX does not evaporate very easily, can be adsorbed into surfaces such as wood, plastic, masonry, paint, and fabric, and is not degraded by sunlight. All of these factors make VX very dangerous, because it can remain in areas for a long time after it has been released, leading to a high potential for exposure.

Approximate color and consistency of VX on a dime. 
Exposure to this amount of VX would be lethal in most individuals.

    The toxicity of VX is impressively high. It can cause death within minutes through exposure by inhalation, ingestion, and through the skin. Since VX does not evaporate very easily, skin absorption is the most significant risk posed to people who are exposed to the chemical. Absorption through the skin can result in symptoms occurring as quickly as one minute after exposure, to as long as 18 hours or more after exposure. 

  Because different individuals have different responses to toxins, one way to measure the toxicity of a particular substance is through a measurement known as the LD50. The LD50 (which stands for "Lethal Dose for 50% of the population") of a particular substance indicates the amount of that substance which, if exposed to a group of individuals, will cause 50% of them to die. The LD50 of VX through the skin is 10 miligrams, which is an amount that corresponds roughly to the size of a small grain of rice on the skin (these measurements were not taken for humans, but were extrapolated from animal models). 

Exposure to 10 miligrams of VX is predicted to cause death in 50% of exposed individuals. 
When converted into volume, this corresponds roughly to a sample the size of a small grain of rice.

    The incredible toxicity of VX comes from its ability to act as an inhibitor for the enzyme acetylcholinesterase (AChE). As described in the Acetylcholinesterase section, an inhibitor works by fitting into the active site of the enzyme and preventing the substrate from binding. This inhibition of AChE causes a large buildup of acetylcholine in the body, (as each AChE enzyme breaks down about 5,000 acetylcholine molecules per second).  Inhibiting AChE will cause a buildup of 5,000 acetylcholine molecules per second per AChE enzyme inhibited, causing a massive buildup of acetylcholine in the synaptic cleft. Normally, this process is temporary, and the inhibitor molecule can be released by the enzyme so that the correct substrate can bind again. However, when VX binds to AChE, it can sometimes become permanently stuck through a process known as "aging," where the shape of VX is changed after it binds to AChE, making it impossible to be removed from the active site. This will result in the enzyme being permanently deactivated.

A trained chemical agent handler holds a sample of VX

    When there is a massive buildup of acetylcholine molecules in the synaptic cleft, all of the acetylcholine receptors will be activated over and over, causing continuous stimulation of the muscles, glands, and parts of the brain. Initial symptoms of VX exposure include miosis (pinpointing of the pupils in the eyes), runny nose, sweating, nausea, vomiting, urination/defecation, weakness, and difficulty breathing. Eventually, loss of consciousness, convulsions, paralysis, and respiratory failure will quickly lead to death. The primary cause of death from nerve agent exposure is usually respiratory failure, due to the deactivation of the muscles used to breathe, constriction of the lungs, and secretions released within the lungs.

A mnemonic device that can be used to remember the effects of nerve agents is SLUDGE, 
which stands for salivation, lacrimation (crying), urination, defacation, gastroenteritis 
(inflammation of the stomach and/or intestine), and emesis (vomiting).

    These effects are seen because of continual stimulation of the muscarinic and nicotinic acetylcholine receptors. Muscarinic receptor effects mainly involve the lungs, heart, pupils, and salivary and sweat glands, and nicotinic receptor effects mainly involve muscles, and result in weakness, diarrhea, fast heartbeat, and seizures.  The effects of VX on the brain include giddiness, anxiety, confusion and depression (though it is harder to study the effects of VX on the brain, because all trials must be done using animal models).


VX stored in steel containers at the Newport Chemical Depot, Indiana, United States

    Once VX has been absorbed through the skin, it is able to get into the bloodstream and travel all over the body. Red blood cells, like some neurons, use acetylcholinesterase as well, and VX can interact with this red blood cell acetylcholinesterase (RBC-AChE). Several studies have suggested that inhibition of RBC-AChE is not thought to result in significant harm for individuals, so after VX enters the bloodstream and interacts with RBC-AChE, the end result is a reduction in the amount of VX that can travel to the nerves and cause the large buildup of acetylcholine that was discussed previously. One of the reasons that VX is much more toxic than other organophosphate nerve agents is because it is less able to bind to enzymes that are not in neurons (such as RBC-AChE), so there will be more VX available to inhibit AChE in the neurons compared to other chemicals that interact more strongly with other enzymes within the body.

Diagram showing how VX travels from the skin to the bloodstream, where it interacts with red blood cell 
acetylcholinesterase before being distributed to the brain, periphery, muscles, and glands.

    Recent studies have suggested that another reason that VX is more toxic than other organophosphate nerve agents is because it can inhibit enzymes other than acetylcholinesterase. It has been proposed that VX damages other neurotransmitter systems, including the norepinephrine, dopamine, and GABA pathways (other important neurotransmitters), and research is currently being conducted to support this idea. However, it is generally agreed upon that inhibition of acetylcholinesterase and the massive buildup of acetylcholine that this causes is the main reason for the high level of toxicity of the orgnophosphate nerve agent VX.