S A R I N

SARIN Brian Buscher [bbuscher@calpoly.edu]
Chemistry 377 - Drugs and Poisons, Spring 2000
Instructor: Dr. Bailey

Please note: The font sizing on this page is designed to change according to the settings of your browser.
I think it looks best on "medium" size or smaller (at 1280x1024). The tables might not look right otherwise.
Of course this will vary with the screen resolution.

[History] [Structure] [Mode of Action] [Symptoms] [Treatment]

A Brief History of Sarin and Other Nerve Agents

Sarin and other nerve agents had their beginnings in Germany in the 1930s. A chemist named Dr. Gerhard Schrader was developing organophosporous insecticides (these compounds were recently discovered to be poisonous). The first of these discovered, tabun, was developed in 1936. The German military immediately saw the potential of this compound and began producing it in a factory in large quantities. The age of the nerve agents had arrived.

Schrader continued his research after the advent of tabun. The German chemists synthesized some 2,000 new organophosphorous compounds during the course of the war and produced a total of 3 new nerve agents-- each given a "G" designation by the Americans-- sarin (GB) in 1938, soman (GD) in 1944, GE and GF (these were not given common names). Tabun was (and still is) referred to as GA.

It is interesting to note that no nerve agents were actually used during the war. Had it been otherwise, the outcome might have been much different.

When the war was over, much research went into ways to protect against the nerve agents. This research led to the discovery of much more deadly compounds (ten times more powerful than sarin) given the designation "V". The most well known of these compounds is VX. Others include VE, VG and VM. These nerve agents are far less volatile than the G agents and will persist in the environment for a much longer time. Obviously, these compounds can be a very deadly threat (or a powerful asset).

While a number of large countries stockpiled the nerve agents in the decades following World War II, the agents have rarely been used in warfare. The only noted exception occurred with Iraq's attack on the Kurds. There have also been allegations that some nerve agents were used during the Iran-Iraq war, but that has not been proven. Sarin was also used in two terrorist attacks in Japan (Matsumoto and Tokyo) in the mid-1990s. [top]

[History] [Structure] [Mode of Action] [Symptoms] [Treatment]

Structure and Properties

Click here to view sarin's molecular structure. You will need Chemscape Chime to view it, which is available at MDL's website.

Sarin (isopropyl methylphosphonofluoridate or methylphosphonofluoridic acid) is the smallest of the organophosphate nerve agents, with a weight of 140.1 g/mol.

Sarin (GB)

Here are the structures of the other important G agents for comparison.

Tabun (GA)


Soman (GD)

Notice the similarities between the three molecules. Each G toxin is a derivative of phosphoric or phosphonic acid and each contains a leaving group (fluorine in the case of sarin) and two alkyl groups. Sarin (and soman) is considerably more difficult to synthesize than tabun, as hydrofluoric acid is required. HF is corrosive to glass so special silver-lined containers were used when first produced in the 1930s. Tabun is much easier to make since HCN is not as hard to work with. It is no coincidence that this is the reason tabun was created first, and is usually the first nerve agent synthesized by countries just entering chemical warfare preparations.

A very real danger concerning sarin is that it is not very difficult to make. Any person with a little knowledge of organic chemistry can synthesize it quite ease. One can use isopropanol, a methylated derivative of phosphoric acid and HF (using caution regarding HF's corrosiveness), and one of the world's most deadly chemicals is formed.

It is possible to combine a nerve agent with a thickening agent to make it persist in the environment longer. This can be done to any of the agents (like sarin), although it is usually done with soman.

Sarin is a colorless liquid that gives off a colorless vapor and has no odor. It is the most volatile of nerve agents, similar to water. It is also very soluble in water (the others are only slightly soluble).

Table 1. Physical Properties of Nerve Agents

Property Tabun Sarin Soman VX

Molecular weight 162.1 140.1 182.2 267.4

Density g/cm³ * 1.073 1.089 1.022 1.008

Boiling-point ^oC 247 147 167 300

Melting-point ^oC -50 -56 -42 -39

Vapor pres. mm Hg * 0.07 2.9 0.3 0.0007

Volatility mg/m³ * 600 17,000 3,900 10

Solubility in water % * 10 oo 2 3 (oo < 9,5 ^oC)

* = at 25 ^oC

Source: OPCW

[top]

[History] [Structure] [Mode of Action] [Symptoms] [Treatment]

Mode of Action

Sarin's primary mode of action is the inhibition of the enzyme acetylcholinesterase (AChE), which destroys acetylcholine (ACh) in the nerve synapse to terminate signal transmission. Sarin phosphorylates a serine hydroxyl group in the AChE and renders it inactive. This will cause a buildup of ACh and the continuous stimulation of the nicotinic and muscarinic receptors. The results of such an action are described in the next section.

Figure 1 shows a pictorial representation of the synapse and the effects of sarin on AChE.

Figure 1. Model of a Cholinergic Synapse

Source: OPCW

As shown in the illustration, the nerve agent binds to acetylcholinesterase (the bumps on the lower portion of the synapse) and makes it unable to break down acetylcholine (the green balls). This results in a compounding excess of ACh that cannot be removed (and hence continuous stimulation of the receptors). [top]

[History] [Structure] [Mode of Action] [Symptoms] [Treatment]

Symptoms

Table 2 shows general effects and symptoms of sarin poisoning.

Table 2. Effects of Sarin at Various Sites of the Body

Receptor

Target organ

Symptoms and signs

Central

Central nervous system

Giddiness, anxiety, restlessness, headache, tremor, confusion, failure to concentrate, convulsions, respiratory depression

Muscarinic

Glands Nasal mucosa Bronchial mucosa Sweat Lacrimal Salivary Smooth muscle Iris Ciliary muscle Gut Bladder Heart

Rhinorrhea Bronchorrhea Sweating Lacrimation Salivation Miosis Failure of accommodation Abdominal cramp, diarrhea Frequency, involuntary micturition Bradycardia

Nicotinic

Autonomic ganglia Skeletal muscle

Sympathetic effects, pallor, tachycardia, hypertension Weakness, fasciculation

Source: Marrs, pg 91

The route of exposure determines the levels of observable effects. Exposure to sarin vapor will result in immediate results, beginning with tightness of the chest, rhinorrhea and salivation. Next the pupils will constrict, causing dimming of vision, eye pain, and headache. Abdominal pain, vomiting, involunatry defecation (sound like fun...), weakness, fasciculation and convulsion may also occur at higher exposure levels. The cause of death in this case is respiratory failure (a very unpleasant form of suffocation).

If sarin comes into contact with the skin, sweating and local fascication is observed. These symptoms may spread and eventually the whole body will react in ways similar to that of vapor contact (albeit in a much longer time period).

If ingested, sarin will cause colicky pain, nausea, vomiting, diarrhea and involuntary defecation. [top]

[History] [Structure] [Mode of Action] [Symptoms] [Treatment]

Treatment

Treatment will have to commence immediately after sarin poisoning (within one minute). Typically the drugs used are atropine, pyridinium oximes and central nervous depressants.

Atropine is a muscarinic cholinergic antagonist, blocking the effects of acetylcholine at muscarinic sites. It will bind to the muscarinic receptors and thus prevent acetylcholine from binding. It does nothing to stop the acetylcholinesterase inhibition so it treats only the symptoms and not the cause. Atropine is administered in 2 mg (and sometimes up to 6 mg) doses intravenously (preferred) or intramuscularly if necessary. This is repeated every ten to fifteen minutes until the victim's heartbeat is over 90 beats a minute and breathing has been eased. Since atropine does not affect the nicotinic receptors, a victim will continue to twitch and fasciculate after treatment.

Pyridinium oximes are usually given with atropine to treat sarin poisoning as it provides a synergistic benefit. Oximes reactivate acetylcholinesterase so it can break down the acetylcholine that is building up. 2-PAMCl (pralidoxime chloride; Protopam chloride) is the drug of choice in the US. Other countries prefer different drugs. For example, P₂S (pralidoxime methanesulfonate) is used in the UK. The recommended dose of 2-PAMCl is 15-25 mg/kg. Autoinjectors may contain up to 600 mg to deliver the recommended dose (see picture below).

An autoinjector that delivers both atropine and a pyridinium oxime.
Source: OPCW,

CNS depressants such as diazepam can help a victim by reducing apprehension, agitation, muscular fasciculation and stopping convulsions. 5 mg is given intravenously (some militaries use tablets) every 15 minutes up to 15 mg maximum. Some autoinjectors now include a dose of diazepam with the atropine and oxime. This limits the possiblility of further sarin exposure, since troops previously had to lift their gasmasks to administer the tablets (when used).

Some research has gone into the possiblility of prohylactically treating sarin poisoning. Generally a diazepam tablet is given to strengthen the effects of antidotes. It also protects against permanent brain damage from heavy exposures to nerve agents. Carbamate pretreatment is also used. It inhibits acetylcholinesterase and keeps it from the inhibitory effects of nerve agents (inhibits about 25% of the nerve agent). Although effective, the prophylactic use of some carbamates have come under scrutiny lately. There are those that believe there may be connections between the use of pyridostigmine bromine tablets (a type of carbamate) during the Gulf War and Gulf War syndrome (An article on that can be read here). In addition to the tablets, some countries also supply a cream that can be applied to the skin to limit poisoning.

Depending on the exposure, a victim may be well enough to resume daily activities withing a week or two, although sometimes several months of treatment is necessary. A patient's mental and visual capabilites need to be evaluated before they are released.

Being a very volatile liquid, sarin is not very difficult to clean up in the environment. It is rapidly hydrolyzed into basic solutions by chemicals such as bleach, DS2 (2% NaOH, 70% diethylenetriamine, 28% ethylene glycol monomethyl ether), and with towelettes moistened with NaOH dissolved in water, phenol, ethanol, and ammonia. Personal decontamination includes removing contaminated clothing and putting a liquid or powder on the skin that absorbs the sarin and breaks it down. Some release chlorine which effectively destroys the sarin. This also is quite hard on the skin, but it sure is better than the sarin! [top]

References and Links

"Does post-traumatic stress disorder explain Gulf War syndrome?" American Chemical Society. http://pubs.acs.org/hotartcl/cenear/980525/syn.html.

Garrett, Reginald and Grisham, Charles. Biochemistry. Second Edition. Saunders College Publishing. 1999.

Marrs, Timothy C. Chemical Warfare Agents: Toxicology and Treatment. John Wiley & Sons Ltd, England. 1996.

"Nerve Agents." Organization for the Prohibition of Chemical Weapons (OPCW). http://www.opcw.nl/chemhaz/nerve.htm.

"Potential Exposure to Sarin..." http://www.gulflink.osd.mil/dugway/low_lv_chem.htm

"Sarin Nerve Gas." http://www.geocities.com/CapeCanaveral/Lab/7050/

Somani, Satu M. Chemical Warfare Agents. Academic Press, Inc. San Diego. 1992.

This page is made by hand exclusively in Windows Notepad. I cannot guarantee complete cross-platform compatibility.
If there are any problems with viewing this site, please email myself or Dr. Bailey (links at top of page).