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The primary mechanism of the toxic action of organophosphorus (OP) nerve agents and pesticides is inhibition of carboxyl ester hydrolase enzymes, of which acetylcholinesterase (AChE) is the most toxicologically important. AChE (EC, also known as true cholinesterase, is a serine protease enzyme that catalyses the hydrolysis of the neurotransmitter acetylcholine (ACh) to choline and acetic acid. AChE is found in the central nervous system (CNS) and peripheral nervous system, neuromuscular junctions (NMJs) and red blood cells (RBCs). Organophosphates inactivate AChE by phosphorylating the serine hydroxyl group located at the active site of the enzyme.

The natural substrate for AChE, ACh, is a neurotransmitter that mediates chemical synaptic transmission at the NMJ, in the peripheral autonomic nervous system and in the CNS. The acute life-threatening toxicity of nerve agents arises from the uncontrolled accumulation of ACh at peripheral and central cholinergic synapses, giving rise to the so-called cholinergic syndrome. This is characterised by peripheral effects [increased secretions, miosis, abdominal cramps, involuntary defecation and urination, changes in heart rate, pallor, muscular weakness, fasciculations (localised muscle contraction), muscular paralysis, tachycardia (increased heart rate) and hypertension] and central effects (giddiness, anxiety, headache, impaired memory and alertness, tremor, convulsions, seizures, and respiratory depression).1,2  Lethality is generally believed to be caused by respiratory paralysis resulting from disruption of the respiratory centres in the brain or from transmission failure at NMJs.3,4 

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