title: Reactivation of cyclosarin-inhibited rat brain acetylcholinesterase by pyridinium--oximes.
abstract: Cyclohexyl methylphosphonofluoridate (cyclosarin, cyclosin, GF) is a highly toxic organophosphate, which is resistant to conventional oxime therapy. To gain insight into the reactivation kinetics, rat brain acetylcholinesterase (AChE) was inhibited in vitro by cyclosarin (pH 8.0, 25 degrees C) and reactivated with 22 different pyridiniumoximes. Three compounds were shown to be superior to the other oximes: 4-carbamoyl-4'-[(hydroxyimino)methyl]-1,1'-(oxydimethylene)dipyridin-1-ium dichloride (HS-6), 4'-carbamoyl-2-[(hydroxyimino)methyl]-1,1'-(oxydimethylene)dipyridin-1-ium dichloride (HI-6), and 4'-carbamoyl-2-[(hydroxyimino)-methyl]-1,1'-(but-2-ene-1,4-diyl)dipyridin-1-ium dichloride (BI-6).
authors.affiliation: Department of Toxicology, Military Medical Academy, Trebesská 1575, 500 01 Hradec Kralove, Czech Republic. kucakam@pmfhk.cz
authors.forename: Kamil
authors.initials: K
authors.lastname: Kuca
authors.forename: Jirí
authors.initials: J
authors.lastname: Patocka
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D002801:Cholinesterase Reactivators / Q000737:chemistry / Q000494:pharmacology*; D007700:Kinetics; D009943:Organophosphorus Compounds / Q000737:chemistry / Q000494:pharmacology*; D010091:Oximes / Q000737:chemistry / Q000494:pharmacology*; D011726:Pyridinium Compounds / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D009943:Organophosphorus Compounds; D010091:Oximes; D011726:Pyridinium Compounds; D000110:Acetylcholinesterase; C053914:cyclohexyl methylphosphonofluoridate