title: Potency of five structurally different acetylcholinesterase reactivators to reactivate human brain cholinesterases inhibited by cyclosarin.
abstract: Acetylcholinesterase (AChE; EC 3.1.1.7) reactivators are used as a part of the antidotal therapy of organophosphorus pesticide and nerve agent intoxications. Cyclosarin is one member of the nerve agent family. In this article, we compared the reactivation potency of five structurally different AChE reactivators (pralidoxime, trimedoxime, methoxime, HS-6, and BI-6) to reactivate cyclosarin-inhibited cholinesterases of human brain. The results demonstrate that the bisquaternary monooxime reactivator BI-6 seems to be the most potent reactivator of cyclosarin-inhibited cholinesterases. Moreover, according to the results, we can describe basic structural requirements, which are necessary for the efficacious reactivation process.
authors.affiliation: Department of Toxicology, Faculty of Military Health Sciences, University of Defense, Hradec Kralove.,Czech Republic. kucakam@pmfhk.cz
authors.forename: Kamil
authors.initials: K
authors.lastname: Kuca
authors.forename: Jiri
authors.initials: J
authors.lastname: Cabal
authors.forename: Daniel
authors.initials: D
authors.lastname: Jun
authors.forename: Martina
authors.initials: M
authors.lastname: Hrabinova
mesh_terms: D000368:Aged; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D002801:Cholinesterase Reactivators / Q000494:pharmacology*; D002802:Cholinesterases / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009943:Organophosphorus Compounds / Q000494:pharmacology; D010091:Oximes / Q000494:pharmacology*; D011220:Pralidoxime Compounds / Q000494:pharmacology*; D011726:Pyridinium Compounds / Q000494:pharmacology*; D014289:Trimedoxime / Q000494:pharmacology
chemical_list: C118647:BI 6; D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D009943:Organophosphorus Compounds; D010091:Oximes; D011220:Pralidoxime Compounds; D011726:Pyridinium Compounds; C003027:HS 6; D014289:Trimedoxime; C005514:N,N'-monomethylenebis(pyridiniumaldoxime); D002802:Cholinesterases; C028797:pralidoxime; C053914:cyclohexyl methylphosphonofluoridate