title: Acetylcholinesterase prophylaxis against organophosphate poisoning. Quantitative correlation between protection and blood-enzyme level in mice.
abstract: Fetal bovine serum acetylcholinesterase (FBS-AChE, EC 3.1.1.7) was titrated, both in vitro and in vivo, with a highly toxic anti-ChE organophosphate, 7-(methylethoxyphosphinyloxy)-1-methyl-quinolinium iodie (MEPQ). Approximately 1:1 stoichiometry was obtained for the sequestration of MEPQ by FBS-AChE in mice. A quantitative, linear correlation was demonstrated between blood-AChE levels and the protection afforded by exogenously administered AChE in mice when challenged with anti-ChE MEPQ. The results presented in this report demonstrate that such prophylactic measures are indeed sufficient to protect animals against poisoning by as high as an 8 x LD50 dose of organophosphate without the administration of any supportive drug. Despite the relatively large toxic dose, most of the mice that survived the challenge did not show any classical clinical signs of severe anti-ChE poisoning. MEPQ may be considered a suitable model compound for studying the quantitative aspects of the scavenger prophylactic approach described here.
authors.affiliation: Division of Biochemistry, Walter Reed Army Institute of Research, Washington, DC 20307-5100.
authors.forename: L
authors.initials: L
authors.lastname: Raveh
authors.forename: Y
authors.initials: Y
authors.lastname: Ashani
authors.forename: D
authors.initials: D
authors.lastname: Levy
authors.forename: D
authors.initials: D
authors.lastname: De La Hoz
authors.forename: A D
authors.initials: AD
authors.lastname: Wolfe
authors.forename: B P
authors.initials: BP
authors.lastname: Doctor
mesh_terms: D000110:Acetylcholinesterase / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000506:poisoning*; D004355:Drug Stability; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D062025:Organophosphate Poisoning; D011806:Quinolinium Compounds / Q000506:poisoning*; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D014289:Trimedoxime / Q000494:pharmacology
chemical_list: D002800:Cholinesterase Inhibitors; D011806:Quinolinium Compounds; D012710:Serum Albumin, Bovine; D014289:Trimedoxime; C044294:7-((methylethoxyphosphinyl)oxy)-1-methylquinolinium; D000110:Acetylcholinesterase