From Pyridinium-based to Centrally Active Acetylcholinesterase Reactivators

Title:From Pyridinium-based to Centrally Active Acetylcholinesterase Reactivators

Volume: 14 Issue: 3

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

Affiliation:

Keywords: Acetylcholinesterase, HI-6, organophosphorus compounds, pyridinium oximes, pralidoxime, reactivator, trimedoxime, uncharged reactivator.

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.

Cite this article as:

Korabecny Jan, Soukup Ondrej, Dolezal Rafael, Spilovska Katarina, Nepovimova Eugenie, Andrs Martin, Nguyen Duong Thuy, Jun Daniel, Musilek Kamil, Kucerova-Chlupacova Marta and Kuca Kamil, From Pyridinium-based to Centrally Active Acetylcholinesterase Reactivators, Mini-Reviews in Medicinal Chemistry 2014; 14 (3) . https://dx.doi.org/10.2174/1389557514666140219103138