title: Substituted monoquaternary oximes as reactivators of cyclosarin--and chlorpyrifos--inhibited acetylcholinesterase.
abstract: This paper describes an in vitro study of three potential acetylcholinesterase (AChE; EC 3.1.1.7) reactivators derived from a monoquaternary reactivator pralidoxime. Compounds used were pyridinium-2-aldoxime-4-carbamoyl-N-methyl iodide (TO231), pyridinium-2-aldoxime-4-ethoxycarbonyl-N-methyl iodide (TO237), and pyridinium-2-aldoxime-5-ethoxycarbonyl-N-methyl iodide (TO238). Pralidoxime and obidoxime were used for comparison. Nerve agent cyclosarin and pesticide chlorpyrifos were used as organophosphorus cholinesterase inhibitors. The source of AChE was rat brain homogenate. None of the tested oximes was able to reactivate cyclosarin-inhibited AChE (at 1.0 mmol L(-1) oxime concentration). In case of chlorpyrifos, TO231 was the most potent AChE reactivator with an 82 % reactivation at 1.0 mmol L(-1) oxime concentration. This reactivating potency equals that of pralidoxime and obidoxime. TO238 was less effective, and TO237 did not reactivate chlorpyrifos-inhibited AChE at all. None of the tested AChE reactivators, reference compounds included, could be considered universal for both chlorpyrifos- and cyclosarin-inhibited AChE.
authors.affiliation: Department of Pharmaceutical Chemistry and Drug Control, Faculty of Pharmacy, Charles University of Prague.
authors.forename: Veronika
authors.initials: V
authors.lastname: Racakova
authors.forename: Martina
authors.initials: M
authors.lastname: Hrabinova
authors.forename: Daniel
authors.initials: D
authors.lastname: Jun
authors.forename: Kamil
authors.initials: K
authors.lastname: Kuca
mesh_terms: D000818:Animals; D000931:Antidotes / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D004390:Chlorpyrifos / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D002801:Cholinesterase Reactivators / Q000494:pharmacology*; D066298:In Vitro Techniques; D009943:Organophosphorus Compounds / Q000378:metabolism*; D010575:Pesticides / Q000378:metabolism* / Q000494:pharmacology; D011220:Pralidoxime Compounds / Q000494:pharmacology*; D051381:Rats
chemical_list: D000931:Antidotes; D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D009943:Organophosphorus Compounds; D010575:Pesticides; D011220:Pralidoxime Compounds; D004390:Chlorpyrifos; C053914:cyclohexyl methylphosphonofluoridate