Non-oxime reactivators of organophosphate-inhibited cholinesterases

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00179906%3A_____%2F25%3A10499748" target="_blank" >RIV/00179906:_____/25:10499748 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/62690094:18470/25:50022381

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=Kx6-pSCfUA" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=Kx6-pSCfUA</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s00204-025-04070-8" target="_blank" >10.1007/s00204-025-04070-8</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Non-oxime reactivators of organophosphate-inhibited cholinesterases

Popis výsledku v původním jazyce

Organophosphorus compounds, including pesticides and nerve agents, irreversibly inhibit acetylcholinesterase, leading to an accumulation of acetylcholine that can cause a cholinergic crisis. Standard treatment of organophosphate poisoning relies on oxime-based reactivators, such as pralidoxime, obidoxime, or asoxime. However, these compounds have several limitations, including poor penetration through the blood-brain barrier and limited efficacy across a broad spectrum of organophosphorus compounds. For this reason, non-oxime reactivators were introduced as potential alternatives. The most promising non-oxime reactivators contain Mannich phenol moiety, imidazole group or combination of both. Some of the non-oxime derivatives demonstrated better efficacy than standard oximes during in vitro evaluation. Nevertheless, these structures have significant drawbacks such as high intrinsic acetylcholinesterase inhibition or high toxicity profile which make them unsuitable for further in vivo tests. In this review, the current progress in the development of non-oxime reactivators is summarized and their bioactivity as well as their limitations are critically discussed.

Název v anglickém jazyce

Non-oxime reactivators of organophosphate-inhibited cholinesterases

Popis výsledku anglicky

Organophosphorus compounds, including pesticides and nerve agents, irreversibly inhibit acetylcholinesterase, leading to an accumulation of acetylcholine that can cause a cholinergic crisis. Standard treatment of organophosphate poisoning relies on oxime-based reactivators, such as pralidoxime, obidoxime, or asoxime. However, these compounds have several limitations, including poor penetration through the blood-brain barrier and limited efficacy across a broad spectrum of organophosphorus compounds. For this reason, non-oxime reactivators were introduced as potential alternatives. The most promising non-oxime reactivators contain Mannich phenol moiety, imidazole group or combination of both. Some of the non-oxime derivatives demonstrated better efficacy than standard oximes during in vitro evaluation. Nevertheless, these structures have significant drawbacks such as high intrinsic acetylcholinesterase inhibition or high toxicity profile which make them unsuitable for further in vivo tests. In this review, the current progress in the development of non-oxime reactivators is summarized and their bioactivity as well as their limitations are critically discussed.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

<a href="/cs/project/GA25-15339S" target="_blank" >GA25-15339S: Enkapsulace biskvarterních oximů do pevných lipidových nanočástic pro zvýšení reaktivace cholinesteras v CNS</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Archives of Toxicology

ISSN

0340-5761

e-ISSN

1432-0738

Svazek periodika

99

Číslo periodika v rámci svazku

8

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

16

Strana od-do

3315-3330

Kód UT WoS článku

001480441300001

EID výsledku v databázi Scopus

2-s2.0-105004192313