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).
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylcholinesterase / metabolism
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Animals
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Brain / drug effects*
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Brain / enzymology
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Cholinesterase Inhibitors / chemistry
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Cholinesterase Inhibitors / pharmacology*
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Cholinesterase Reactivators / chemistry
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Cholinesterase Reactivators / pharmacology*
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Kinetics
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Organophosphorus Compounds / chemistry
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Organophosphorus Compounds / pharmacology*
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Oximes / chemistry
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Oximes / pharmacology*
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Pyridinium Compounds / chemistry
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Pyridinium Compounds / pharmacology*
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Rats
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Structure-Activity Relationship
Substances
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Cholinesterase Inhibitors
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Cholinesterase Reactivators
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Organophosphorus Compounds
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Oximes
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Pyridinium Compounds
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Acetylcholinesterase
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cyclohexyl methylphosphonofluoridate