Reactivation of cyclosarin-inhibited rat brain acetylcholinesterase by pyridinium--oximes.
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).
Kuca
Kamil
K
Department of Toxicology, Military Medical Academy, Trebesská 1575, 500 01 Hradec Kralove, Czech Republic. kucakam@pmfhk.cz
Patocka
Jirí
J
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
D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D009943:Organophosphorus Compounds; D010091:Oximes; D011726:Pyridinium Compounds; D000110:Acetylcholinesterase; C053914:cyclohexyl methylphosphonofluoridate