Acetylcholinesterase (AChE) inhibitors act on the enzyme AChE, which deactivates acetylcholine at the neuromuscular junction. The system also includes butyrylcholinesterase (BChE), which inactivates butyrylcholine in plasma. For purposes of this chapter, AChE and BChE are considered together and referred to as AChE (2).

Acetylcholine transmits electrochemical impulses across neuronal synapses and neuromuscular junctions and is hydrolyzed by the action of the enzyme acetylcholinesterase. The toxic effects of CM and OP agents result from their ability to inhibit the catalytic activity of AChE in the nervous system by forming covalent bonds to acetylcholine receptors and preventing hydrolysis of acetylcholine by the enzyme (2,3).

The complexes formed between these poisons and the enzymes are hydrolyzed slowly in the case of the carbamoylated enzymes (deactivated by carbamates) or not at all with some phosphorylated enzymes (deactivated by organophosphates), thereby prolonging the action of acetylcholine. Enzyme activity returns only after a period of days or weeks, when new AChE molecules are synthesized.

Acetylcholinesterase activity depression is dose dependent, and there are differences in rates of inactivation and recovery between the plasma and red blood cell (RBC) enzymes (2).

Genetic influences not related to gender, race, or age account for a 23% variation in AChE activity levels among humans. Two types of AChE receptors exist: nicotinic, which are excitatory, and muscarinic, which produce either an excitatory or inhibitory postsynaptic potential.

The 23% variation of AChE activity levels among humans mandates that a baseline be obtained before OP or CM exposure and ongoing AChE testing. AChE activity levels can also be affected by cocaine, pharmaceuticals, and illness (2-4).

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