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Pralidoxime – the gold standard of acetylcholinesterase reactivators – reac­tivation in vitro efficacy

Journal article
Authors Kamil Kuca
M Hrabinova
Ondrej Soukup
Gunnar Tobin
Jana Zdarova Karasova
Miroslav Pohanka
Published in Bratislava Medical Journal
Volume 111
Issue 9
Pages 502-504
ISSN 0006-9248
Publication year 2010
Published at Institute of Neuroscience and Physiology, Department of Pharmacology
Pages 502-504
Language en
Links www.bmj.sk/2010/11109-07.pdf
Keywords cholinesterase, reactivator, oxime, inhibitor, pralidoxime
Subject categories Pharmacology

Abstract

Objective: In this work, we aim to summarize the universality of this compound, its reactivation potential when different cholinesterase inhibitors are used. Background: Pralidoxime is considered as a gold standard of acetylcholinesterase reactivators - antidotes used in case of nerve agent poisonings. It has been commercially available for many years. However, several studies deem this oxime an old-fashion antidote. Methods: Pralidoxime was synthesized at our department. The reactivating efficacy was tested on 10 % (w/v) rat brain homogenate that had been incubated with appropriate inhibitor for 30 minutes to reach 96 % inhibition of AChE. Then, pralidoxime was added for 10 minutes. Measurements were performed at 25 °C, pH 8, and 10-3and 10-5M concentrations of AChE reactivators. The activities of brain AChE were measured by a potentio-static method. Results: No sufficient reactivation was achieved at the concentration of 10-5 M, which is a concentration that can be reached after administration of therapeutic doses. At a higher dose (10-3 M), pralidoxime reactivated AChE inhibited by paraoxon, chlorpyrifos, Russian VX, VX and sarin. Conclusion: From the obtained results, it is clear that pralidoxime seems to be a poor reactivator of AChE inhibited by organophosphorous AChE inhibitors and thus cannot be labeled as a universal reactivator.

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