Usefulness of administration of non-organophosphate cholinesterase inhibitors before acute exposure to organophosphates: Assessment using paraoxon

Georg A. Petroianu, Syed M. Nurulain, Mohamed Shafiullah, Mohamed Y. Hasan, Kamil Kuča, Dietrich E. Lorke

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)894-900
Number of pages7
JournalJournal of Applied Toxicology
Volume33
Issue number9
DOIs
Publication statusPublished - Sep 2013

Keywords

  • Carbamates
  • Cholinesterase
  • Cox analysis
  • Organophosphate
  • Oximes
  • Paraoxon
  • Pre-treatment
  • Rat

ASJC Scopus subject areas

  • Toxicology

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