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Mini-Reviews in Medicinal Chemistry
ISSN (Print): 1389-5575
ISSN (Online): 1875-5607
VOLUME: 14
ISSUE: 3
DOI: 10.2174/1389557514666140219103138      Price:  $58









From Pyridinium-based to Centrally Active Acetylcholinesterase Reactivators

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Author(s): Jan Korabecny, Ondrej Soukup, Rafael Dolezal, Katarina Spilovska, Eugenie Nepovimova, Martin Andrs, Thuy Duong Nguyen, Daniel Jun, Kamil Musilek, Marta Kucerova-Chlupacova and Kamil Kuca
Pages 215-221 (7)
Abstract:
Organophosphates are used as pesticides or misused as warfare nerve agents. Exposure to them can be fatal and death is usually caused by respiratory arrest. For almost six decades, pyridinium oximes represent a therapeutic tool used for the management of poisoning with organophosphorus (OP) compounds. However, these compounds possess several drawbacks. Firstly, they are inefficient in the restoration of brain acetylcholinesterase (AChE) activity due to a hard blood-brain barrier penetration. Secondly, there is no broad-spectrum AChE reactivator. Lastly, none of the oximes can reactivate “aged” AChE. In this context, uncharged reactivators represent a new hope in a way of increased bioavailability in the central compartment and better therapeutic management of the OP poisoning.
Keywords:
Acetylcholinesterase, HI-6, organophosphorus compounds, pyridinium oximes, pralidoxime, reactivator, trimedoxime, uncharged reactivator.
Affiliation:
University Hospital Hradec Kralove, Sokolska 581, 500 05 Hradec Kralove, Czech Republic.