title: In vitro reactivation of trichlorfon-inhibited butyrylcholinesterase using HI-6, obidoxime, pralidoxime and K048.
abstract: Trichlorfon is a specific inhibitor of cholinesterases. It was typically used as an insecticide; however, trichlorfon was described as useful for symptomatic treatment of Alzheimer's disease some years ago. The presented study is aimed at reactivation of trichlorfon-inhibited butyrylcholinesterase since this enzyme play an important role in Alzheimer's disease as deputy for acetylcholinesterase and furthermore it could be applied as a scavenger in case of overdosing. We used in vitro reactivation test for considering only reactivation efficacy of butyrylcholinesterase that is inhibited by trichlorfon and not reactivation of butyrylcholinesterase inhibited by trichlorfon metabolic products. Four reactivators were used: HI-6, pralidoxime, obidoxime, and K048. Although all of the reactivators seem to be effective at 1 mM concentration, a lower concentration was not able ensure sufficient reactivation. There was also an observed lowering of reactivation efficacy when butyrylcholinesterase was exposed to trichlorfon for a longer time interval.
authors.affiliation: Faculty of Military Health Sciences, Center of Advanced Studies, University of Defence, Hradec Kralove, Czech Republic.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Pohanka
authors.forename: Daniel
authors.initials: D
authors.lastname: Jun
authors.forename: Kamil
authors.initials: K
authors.lastname: Kuca
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D002091:Butyrylcholinesterase / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D002801:Cholinesterase Reactivators / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D009768:Obidoxime Chloride / Q000494:pharmacology*; D010091:Oximes / Q000494:pharmacology*; D011220:Pralidoxime Compounds / Q000494:pharmacology*; D011726:Pyridinium Compounds / Q000494:pharmacology*; D014236:Trichlorfon / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: C488676:1-(4-hydroxyiminomethylpyridinium)-4-(4-carbamoylpyridinium)butane; D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D010091:Oximes; D011220:Pralidoxime Compounds; D011726:Pyridinium Compounds; D009768:Obidoxime Chloride; D014236:Trichlorfon; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; C022870:asoxime chloride; C028797:pralidoxime