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, an enzyme that catalyzes the breakdown of acetylcholine, a neurotransmitter.Speer, who was strongly opposed to the introduction of tabun, flew Otto Ambros, I.G.'s authority on poison gas as well as synthetic rubber, to the meeting. Hitler asked Ambros, 'What is the other side doing about poison gas?' Ambros explained that the enemy, because of its greater access to ethylene, probably had a greater capacity to produce mustard gas than Germany did. Hitler interrupted to explain that he was not referring to traditional poison gases: 'I understand that the countries with petroleum are in a position to make more , but Germany has a special gas, tabun. In this we have a monopoly in Germany.' He specifically wanted to know whether the enemy had access to such a gas and what it was doing in this area. To Hitler's disappointment Ambros replied, 'I have justified reasons to assume that tabun, too, is known abroad. I know that tabun was publicized as early as 1902, that Sarin was patented and that these substances appeared in patents. ' (...)Ambros was informing Hitler of an extraordinary fact about one of Germany's most secret weapons. The essential nature of tabun and sarin had already been disclosed in the technical journals as far back as 1902 and I.G. had patented both products in 1937 and 1938. Ambros then warned Hitler that if Germany used tabun, it must face the possibility that the Allies could produce this gas in much larger quantities. Upon receiving this discouraging report, Hitler abruptly left the meeting. The nerve gases would not be used, for the time being at least, although they would continue to be produced and tested. 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, an enzyme that catalyzes the breakdown of acetylcholine, a neurotransmitter. 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 to amber-colored, 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. 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 muscle contraction. If the agent cannot be broken down, muscles are prevented from relaxing and they are effectively paralyzed.:131–139 This includes the heart and the muscles used for breathing. Because of this, the first symptoms usually appear within seconds of exposure and death can occur via asphyxiation or cardiac arrest in a few minutes. 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 suffer 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. 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.