Acetylcholine esterase inhibitors AChE

Autopsy studies on Alzheimer-afflicted brains some 40 years later showed a similar huge drop in neurotransmitter levels, but this time it was acetylcholine (ACh) in the hippocampus —which is associated with memory. Choline-esterase inhibitors, which stop the breakdown of ACh, were introduced and are presently the only symptom treatment available (Aricept, Excelon, Reminyl, Cognex). Recently, in 2004, memantine was approved as the first treatment to slow progression of Alzheimer s in mild to moderate cases. Work is ongoing to define acetylcholine-like muscarinic M-1 agonists and M-2 agonists that act on acetylcholine receptors directly. 

In the CNS, acetylcholine esterase (AChE) plays a fundamental role in the regulation of neuronal activity by hydrolyzing the neurotransmitter acetyl-chohne after its release in the intersynaptic space. The AChE enzyme was first targeted by nerve gases and pesticides, but therapeutic appHcations have also been explored, and several reversible AChE inhibitors have... 

Metabolites that are less reactive than suicide inhibitors may impact more distant enzymes, within the same cell, adjacent cells, or even in other tissues and organs, far removed from the original site of primary metabolism. For example, organopho-sphates (OPs), an ingredient in many pesticides, are metabolized by hepatic CYPs to intermediates, which, when transported to the nervous system, inhibit esterases that are critical for neural function. Acetylcholinesterase (AChE) catalyzes the hydrolysis of the ester bond in the neurotransmitter, acetylcholine, allowing choline to be recycled by the presynaptic neurons. If AChE is not effectively hydrolyzed by AChE in this manner, it builds up in the synapse and causes hyperexcitation of the postsynaptic receptors. The metabolites of certain insecticides, such as the phos-phorothionates (e.g., parathion and malathion) inhibit AChE-mediated hydrolysis. Phosphorothionates contain a sulfur atom that is double-bonded to the central phosphorus. However, in a CYP-catalyzed desulfuration reaction, the S atom is... 

The wide use of cholinesterase inhibitors in various spheres of human activities and the risk of acute and chronic intoxications associated with this process prompted investigation of the role of acetylcholinesterase (AChE) and nonspecific esterases in the immunotropic effects of these chemicals. They irreversibly bind to AChE that normally catalyzes the hydrolysis of acetylcholine (ACh) at the... 

Potentiometric devices have a relatively high sensitivity and selectivity and abroad response range. They are also simple, rehable, and inexpensive and use commonly available instrumentation. Potentiometric enzyme-based biosensor systems have been recently reviewed. The most general approach for the determination of OP compounds (OPCs) is based on their inhibition of the activity of choline esterase enzymes. The presence of low concentrations of inhibitors strongly and specifically affects the enzyme activity. Therefore, by measuring the enzyme activity, the concentration of the OPCs can be assayed. Different enzymes, such as acetylcholine (ACh), BuCh, and, most often, pH sensors, were used as transducers in potentiometric biosensors. 

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