title: From pyridinium-based to centrally active acetylcholinesterase reactivators.
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.
authors.forename: Jan
authors.initials: J
authors.lastname: Korabecny
authors.forename: Ondrej
authors.initials: O
authors.lastname: Soukup
authors.forename: Rafael
authors.initials: R
authors.lastname: Dolezal
authors.forename: Katarina
authors.initials: K
authors.lastname: Spilovska
authors.forename: Eugenie
authors.initials: E
authors.lastname: Nepovimova
authors.forename: Martin
authors.initials: M
authors.lastname: Andrs
authors.forename: Thuy Duong
authors.initials: TD
authors.lastname: Nguyen
authors.forename: Daniel
authors.initials: D
authors.lastname: Jun
authors.forename: Kamil
authors.initials: K
authors.lastname: Musilek
authors.forename: Marta
authors.initials: M
authors.lastname: Kucerova-Chlupacova
authors.affiliation: University Hospital Hradec Kralove, Sokolska 581, 500 05 Hradec Kralove, Czech Republic. kamil.kuca@fnhk.cz.
authors.forename: Kamil
authors.initials: K
authors.lastname: Kuca
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D002801:Cholinesterase Reactivators / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D055808:Drug Discovery; D006801:Humans; D062025:Organophosphate Poisoning / Q000188:drug therapy; D011726:Pyridinium Compounds / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D002801:Cholinesterase Reactivators; D011726:Pyridinium Compounds; D000110:Acetylcholinesterase