title: Oxime-induced reactivation of acetylcholinesterase inhibited by phosphoramidates.
abstract: The reaction of human erythrocyte acetylcholinesterase (AChE) with a set of structurally related phosphoramidates was studied in order to investigate the properties of phosphorylated enzyme and the effects of 4 oximes PAM-2, TMB-4, HI-6 and BDB-106 on the reactivation of inhibited AChE. Second-order rate constant of the phosphorylation reaction of the compounds towards the active site of AChE range between 5.0 x 10(2) and 4.9 x 10(6) M-1min-1 and their inhibitory power (I50) was from 7.3 x 10(-5) to 5.7 x 10(-9) M for 20 min incubation at 37 degrees C. The oximes used were weak reactivators of inhibited AChE except for (C4H9O)(NH2)P(O)DCP (DCP, -O-2,5-dichlorphenyl group) and (C6H13O)(NH2)P(O)SCH3 where we have obtained good reactivation. Imidazole oxime BDB-106 proved to be a potent reactivator of tabun-inhibited AChE.
authors.affiliation: Faculty of Pharmacy, Department of Toxicology, Belgrade, Yugoslavia.
authors.forename: M
authors.initials: M
authors.lastname: Jokanović
authors.forename: M
authors.initials: M
authors.lastname: Maksimović
authors.forename: V
authors.initials: V
authors.lastname: Kilibarda
authors.forename: D
authors.initials: D
authors.lastname: Jovanović
authors.forename: D
authors.initials: D
authors.lastname: Savić
mesh_terms: D000110:Acetylcholinesterase / Q000097:blood / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D002801:Cholinesterase Reactivators / Q000737:chemistry / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D007700:Kinetics; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D010091:Oximes / Q000737:chemistry / Q000494:pharmacology*; D011726:Pyridinium Compounds / Q000494:pharmacology; D014289:Trimedoxime / Q000494:pharmacology
chemical_list: D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D009943:Organophosphorus Compounds; D010091:Oximes; D011726:Pyridinium Compounds; D014289:Trimedoxime; D000110:Acetylcholinesterase; C022870:asoxime chloride