Cholinergic system Acetylcholinesterase inhibition

Organophosphate Ester Hydraulic Fluid. The most widely examined target of organophosphate ester hydraulic fluids is the nervous system. Two types of neurological effects have been observed following exposure to certain organophosphate ester hydraulic fluids cholinergic symptoms associated with acetylcholinesterase inhibition and delayed neuropathy (OPIDN). 

Tsukada H, Nishiyama S, Fukumoto D, Ohba H, Sato K, Kakiuchi T (2004) Effects of acute acetylcholinesterase inhibition on the cerebral cholinergic neuronal system and cognitive function functional imaging of the conscious monkey brain using animal PET in combination with microdialysis. Synapse 52 1-10. 

There are two t)y)es of ChEs, acetylcholinesterase (AChE EC 3.1.1.7) and butyrylcholinesterase (BChE EC.3.1.1.8). AChE plays a major role in the cholinergic system terminating the action of the neurotransmitter acetylcholine (ACh). Inhibition of AChE leads to accumulation of ACh in synapses and blockade of cholinergic... 

Perhaps the most prominent and well-studied class of synthetic poisons are so-called cholinesterase inhibitors. Cholinesterases are important enzymes that act on compounds involved in nerve impulse transmission - the neurotransmitters (see the later section on neurotoxicity for more details). A compound called acetylcholine is one such neurotransmitter, and its concentration at certain junctions in the nervous system, and between the nervous system and the muscles, is controlled by the enzyme acetylcholinesterase the enzyme causes its conversion, by hydrolysis, to inactive products. Any chemical that can interact with acetylcholinesterase and inhibit its enzymatic activity can cause the level of acetylcholine at these critical junctions to increase, and lead to excessive neurological stimulation at these cholinergic junctions. Typical early symptoms of cholinergic poisoning are bradycardia (slowing of heart rate), diarrhea, excessive urination, lacrimation, and salivation (all symptoms of an effect on the parasympathetic nervous system). When overstimulation occurs at the so-called neuromuscular junctions the results are tremors and, at sufficiently high doses, paralysis and death. 

Comparative Toxicokinetics. Diazinon, an anticholinesterase organophosphate, inhibits acetylcholinesterase in the central and peripheral nervous system resulting in cholinergic symptoms, in some... 

Unlike the systemic direct-acting cholinergic stimulants (e.g., bethanechol), cholinesterase inhibitors display a relative lack of specificity regarding which cholinergic synapses they stimulate. These drugs tend to inhibit the acetylcholinesterase found at... 

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