Cholinesterases, a Target of Pharmacology and Toxicology

Abstract

Background. Cholinesterases are a group of serine hydrolases that split the neurotransmitter acetylcholine (ACh) and terminate its action. Of the two types, butyrylcholinesterase and acetylcholinesterase (AChE), AChE plays the key role in ending cholinergic neurotransmission. Cholinesterase inhibitors are substances, either natural or man-made that interfere with the break-down of ACh and prolong its action. Hence their relevance to toxicology and pharmacology.Methods and Results. The present review summarizes current knowledge of the cholinesterases and their inhibition. Particular attention is paid to the toxicology and pharmacology of cholinesterase-related inhibitors such as nerve agents (e.g. sarin, soman, tabun, VX), pesticides (e.g. paraoxon, parathion, malathion, malaoxon, carbofuran), selected plants and fungal secondary metabolites (e.g. aflatoxins), drugs for Alzheimer's disease (e.g. huperzine, metrifonate, tacrine, donepezil) and Myasthenia gravis (e.g. pyridostigmine) treatment and other compounds (propidium, ethidium, decamethonium).Conclusions. The crucial role of the cholinesterases in neural transmission makes them a primary target of a large number of cholinesterase-inhibiting drugs and toxins. In pharmacology, this has relevance to the treatment of neurodegenerative disorders.

Valores de referencia basados en el contexto genético de la actividad enzimática colinesterasa en una población colombiana: un paso hacia el diagnóstico personalizado

“…This process is important to prevent an overstimulation of muscles due to the buildup of acetylcholine in the neuromuscular junction and thus muscle spasms that can lead to death. Cholinesterases are divided into two classes based on differences in their substrate specificity, susceptibility to various kinds of inhibitors and tissue distribution: acetylcholinesterase (AChE; EC 3.1.1.7) and butyrylcholinesterase (BChE; EC 3.1.1.8) (1).…”

Malathion Neurotoxic Effects on Dopaminergic System in Mice: Role of Inflammation

“…acute toxicity, which involves acute cholinergic crisis due to accumulation of acetyl choline as a result of inhibition of cholinesterase (ChE) enzyme [5]. On the other hand, many reports stated that OPs neurotoxicity (especially in case of chronic exposure) may occur in the absence of ChE inhibition [6][7][8].…”

Butyrylcholinesterase as a biochemical marker

“…However, it is not correct as evidence of some signifi cant mechanisms related to BChE has been established. The understanding of the role of BChE in the body is complicated by the fact that unlike AChE, BChE has no unique physiological substrate (1). The evidence of BChE was expected to be found once butyrylcholinesterase knockout animals were prepared.…”

“…A part of central and peripheral nervous system based on cholinergic neurotransmission is called the cholinergic system, and AChE is an invincible part of the system. The system plays the key role in processes such as memory, immunity regulation, and vegetative organs regulation (1). Some pathological processes are linked to the cholinergic system.…”

“…E.g. Alzheimer´s disease, myasthenia gravis, schizophrenia and infl ammation can be treated by drugs affecting the cholinergic system (1)(2)(3).…”