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What is the mechanism of acetylcholinesterase inhibition?
The simple and widely accepted mechanism of acetyl-cholinesterase inhibition is the law of mass action. Large amounts of acetylcholine at the neuromuscular junction secondary to inhibition of acetylcholinesterase increase the interactions between acetylcholine and its postjunctional receptor. Excess acetylcholine effectively competes with nondepolarizing muscle relaxants for nicotinic receptor binding sites on the postjunctional membrane. Additionally, quaternary amines appear to exert a direct stimulatory action on skeletal muscle. Denervated muscle or muscle whose nerve terminals lack acetylcholine con-tract after exposure to quaternary acetylcholinesterase inhibitors, implying a direct action by these agents. Also, acetylcholinesterase inhibitors can convert a single action potential in a motor nerve into a pattern of repetitive firing. This repetitive firing may spread retrograde up the axon, causing other nerves in the same motor unit to fire. This results in increased muscular contraction.
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