Reversible cholinesterase inhibitors as pretreatment for exposure to organophosphates. A review

Journal of Applied Toxicology : JAT
D E Lorke, G A Petroianu

Abstract

Organophosphorus compounds (OPCs), inhibitors of acetylcholinesterase (AChE), are useful agents as pesticides, but also represent a serious health hazard. Standard therapy with atropine and established oxime-type enzyme reactivators (pralidoxime, obidoxime) is unsatisfactory. Better therapeutic results are obtained, when reversible AChE inhibitors are administered before OPC exposure. This review summarizes the history of such a pretreatment approach and sums up a set of experiments undertaken in search of compounds that are efficacious when given before a broad range of OPCs. The prophylactic efficacy of 10 known AChE inhibitors, either already used clinically for different indications (physostigmine, pyridostigmine, ranitidine, tiapride, tacrine, amiloride, metoclopramide, methylene blue) or developed for possible therapeutic use in the future (7-methoxytacrine, K-27) was compared, when administered before exposure to six chemically diverse OPCs in the same experimental setting: ethyl-paraoxon, methyl-paraoxon, diisopropylfluorophosphate, terbufos sulfone, azinphos-methyl and dicrotophos. The experimental oxime K-27 was the most efficacious compound, affording best protection, when administered before terbufos sulfone, azinph...Continue Reading

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Citations

Apr 2, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Dietrich E LorkeGeorg A Petroianu
Jul 16, 2020·Journal of Applied Toxicology : JAT·Eniko Manek, Georg A Petroianu
Jul 3, 2019·Journal of Applied Toxicology : JAT·Dietrich E LorkeGeorg A Petroianu
Nov 14, 2020·Critical Reviews in Toxicology·Maria Alozi, Mutasem Rawas-Qalaji
Apr 4, 2021·International Journal of Molecular Sciences·Dietrich E LorkeGeorg A Petroianu
May 11, 2021·Environmental Science and Pollution Research International·José Francisco Herrera-MorenoAurora Elizabeth Rojas-García
Dec 19, 2020·Current Drug Metabolism·Steven X HuKenneth L Feenstra

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