title: Usefulness of administration of non-organophosphate cholinesterase inhibitors before acute exposure to organophosphates: assessment using paraoxon.
abstract: Reversible acetylcholinesterase (AChE) inhibitors can protect against the lethal effects of irreversible organophosphorus AChE inhibitors (OPCs), when administered before OPC exposure. We have assessed in vivo the mortality-reducing efficacy of a group of known AChE inhibitors, when given in equitoxic dosage before exposure to the OPC paraoxon. Protection was quantified in rats by determining the relative risk (RR) of death. Best in vivo protection from paraoxon-induced mortality was observed after prophylactic administration of physostigmine (RR = 0.30) or the oxime K-27 (RR = 0.34); both treatments were significantly superior to the pre-treatment with all other tested compounds, including the established substance pyridostigmine. Tacrine (RR = 0.67), ranitidine (RR = 0.72), pyridostigmine (RR = 0.76), tiapride (RR = 0.80) and 7-MEOTA (RR = 0.86) also significantly reduced the relative risk of paraoxon-induced death, but to a lesser degree. Methylene blue, amiloride and metoclopramide had an unfavorable effect (RR ≥ 1), significantly increasing mortality. When CNS penetration by prophylactic is undesirable K-27 is a promising alternative to pyridostigmine.
authors.affiliation: Department of Cellular Biology & Pharmacology, Florida International University, Miami, FL 33199, USA. georg.petroianu@fiu.edu
authors.forename: Georg A
authors.initials: GA
authors.lastname: Petroianu
authors.forename: Syed M
authors.initials: SM
authors.lastname: Nurulain
authors.forename: Mohamed
authors.initials: M
authors.lastname: Shafiullah
authors.forename: Mohamed Y
authors.initials: MY
authors.lastname: Hasan
authors.forename: Kamil
authors.initials: K
authors.lastname: Kuča
authors.forename: Dietrich E
authors.initials: DE
authors.lastname: Lorke
mesh_terms: D000818:Animals; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D007928:Lethal Dose 50; D008297:Male; D062025:Organophosphate Poisoning / Q000517:prevention & control*; D010091:Oximes / Q000008:administration & dosage; D010261:Paraoxon / Q000008:administration & dosage* / Q000633:toxicity; D010830:Physostigmine / Q000008:administration & dosage; D011729:Pyridostigmine Bromide / Q000008:administration & dosage; D011899:Ranitidine / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D013619:Tacrine / Q000008:administration & dosage; D063325:Tiapride Hydrochloride / Q000008:administration & dosage
chemical_list: D002800:Cholinesterase Inhibitors; D010091:Oximes; D013619:Tacrine; D063325:Tiapride Hydrochloride; D011899:Ranitidine; D010830:Physostigmine; D011729:Pyridostigmine Bromide; D010261:Paraoxon