Sarin An AchE Inhibitor

German scientists discovered Sarin gas in 1938. They quickly understood the significance of the compound as a potent acetylcholinesterase ( AchE) inhibitor. Inhibiting AchE may cause one of the worst deaths imaginable. The government of Nazi Germany manufactured Sarin gas as a chemical weapon on an industrial scale. The eve of World War One was still the forethought of contemporary 1930s culture. Chemical weapons were used extensively during that war. Chemical Weapons such as mustard gas, phosgene, and chlorine resulted in approximately 100,000 deaths and over 1,000,000 casualties during the war. Nazi Germany assembled a stockpile of Sarin large enough to kill every human on earth. Adolf Hitler, in command of the German Military, did not use morally opposed to its effects. 

Sarin Gas inhibits acetylcholinesterase (AchE). AchE is an inhibitor of acetylcholine (Ach). The significance is due to using Ach as a neurotransmitter in the central nervous system (CNS) and peripheral nervous system (PNS). This paper will focus on its effects on the PNS, specifically the cholinergic system. The cholinergic system is a series of Ach receptors that govern muscle movement. The nicotinic cholinergic system is Ach receptors found in skeletal muscles. The muscarinic cholinergic system comprises Ach receptors in smooth muscle tissue. Ach is used as a chemical signal or neurotransmitter to relay the action potential from nervous tissue to muscle tissue in the cholinergic system. 

The significance of Ach happens at the neuromuscular junction. It is the synaptic connection of the motor nerve to the muscle tissue. Ach receptors are found in skeletal, smooth, and cardiac muscle tissue. A motor nerve undergoes demyelination into 100 – 200 nerve endings. These nerve endings are also called nerve terminals. 

The nerve terminal’s Action potential or electrical signal causes an influx of Calcium ions. As calcium increases, this causes exocytosis of Ach from the presynaptic membrane (the nerve ending). The synaptic cleft is a space of about 50 nm. Ach is released and travels the synaptic cleft. It interacts with the Ach receptors of the postsynaptic membrane, the motor end plate. The motor end plate is a raised platform of folds on the sarcolemma of the muscle cell. This is where the Ach, the chemical signal, is converted into an electrical signal or action potential. The potential at the post synaptic cleft changes from 90 mV to -45 mV. 

The action potential then spreads across and over the surface of the muscle membrane. The action potential releases calcium. Calcium causes actin and myosin to form cross bridges. This is muscle contraction. Acetylcholinesterase inhibits Ach at the postsynaptic receptor, preventing sustained muscle contraction. Sarin Gas prevents the disinhibition of Ach. Ach will accumulate in the neuromuscular junction of every skeletal, smooth, and cardiac cell of the body. As Ach accumulates, every muscle tissue will begin to contract. As this happens, death will soon occur. 

The death of Sarin is violent.

Muscarinic cholinergic toxicity will occur. As your smooth muscles begin to contract, you will defecate, urinate, and vomit. The lining of your respiratory system will contract. Airways, nasal passages, and throat will become constricted. The stomach, bladder, and uterus will contract, violently spasming. The ducts of the eyes will constrict, and tears will form. 

Nicotinic cholinergic toxicity will also occur. As your skeletal muscles begin to contract, the tissue will appear to be rippling. Muscle cramps will form in every muscle in the body. No longer will the diaphragm be able to pull air into the lungs. Death will come from suffocation. As your cardiac cells begin to contract irregularly, tachycardia will become present. With such irregular heartbeats, blood pressure will drop, and lightheadedness will occur. 

Death will present itself as every muscle of the body begins to tear from the point of origin and insertion. No longer does homeostasis occur. The body is now at the extremes: the brink of death.

Treatment must be rapid. Treatment must focus on every avenue of approach. Medical personnel must don personal protective equipment or PPE. Atropine must be administered, and it is a competitive antagonist of Ach. Forcing Ach out of its receptor as atropine has a stronger affinity to the same. Pralidoxime must also be administered. Pralidoxime will release the sarin molecule from AchE, reactivating the enzyme. Therefore, both Atropine and Pralidoxime, as they are administered together, will reverse the effects of the nerve agent.

If seizures are present, Ativan must be administered. Ativan is a benzodiazepine, a depressant and anti-convulsant. If respiratory arrest occurs, mechanical ventilation must also be established. Cardiac dysrhythmia medications may also be administered to control heartbeat and prevent tachycardia. The acute cholinergic toxicity has now passed. 

Sarin was a compound that Adolf Hitler refused to use as the 3rd Reich crumbled into a two-front war. The chemical weapons of World War One did not compare to Sarin. Every muscle of the body will constrict until death occurs. The horrors of Sarin alone did not prevent studying the compound and pharmaceutical propagation of such a dangerous substance. Today, modern pesticides, such as DDT, are derived from Sarin. As of 2022, 300,000 deaths a year occur from pesticides derived from Sarin. Any compound that is directly involved with the process of muscle contraction should be treated with respect, caution, and extreme care.