Efficient detoxification of nerve agents by oxime-assisted reactivation of acetylcholinesterase mutants.

Efficient detoxification of nerve agents by oxime-assisted reactivation of acetylcholinesterase mutants. Neuropharmacology. 2020 Apr 22;:108111 Authors: Kovarik Z, Hrvat NM Abstract The recent advancements in crystallography and kinetics studies involving reactivation mechanism of acetylcholinesterase (AChE) inhibited by nerve agents have enabled a new paradigm in the search for potent medical countermeasures in case of nerve agents exposure. Poisonings by organophosphorus compounds (OP) that lead to life-threatening toxic manifestations require immediate treatment that combines administration of anticholinergic drugs and an aldoxime as a reactivator of AChE. An alternative approach to reduce the in vivo toxicity of OP centers on the use of bioscavengers against the parent organophosphate. Our recent research showed that site-directed mutagenesis of AChE can enable aldoximes to substantially accelerate the reactivation of OP-enzyme conjugates while dramatically slowing down rates of OP-conjugate dealkylation (aging). Therefore, this review focuses on oxime-assisted catalysis by AChE mutants that provides a potential means for degradation of organophosphates in the plasma before reaching the cellular target site. PMID: 32333945 [PubMed - as supplied by publisher]
Source: Neuropharmacology - Category: Drugs & Pharmacology Authors: Tags: Neuropharmacology Source Type: research