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

Authors

  • Georg A. Petroianu,

    Corresponding author
    1. Department of Cellular Biology & Pharmacology, Florida International University, Miami, FL, USA
    2. Department of Pharmacology & Therapeutics, FMHS, UAE University, Al Ain, United Arab Emirates
    • Correspondence to: G. A. Petroianu, College of Medicine, Florida International University, Department of Cellular Biology & Pharmacology, University Park GL 495 E, 11200 SW 8th St, Miami 33199, FL, USA. E-mail: georg.petroianu@fiu.edu

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  • Syed M. Nurulain,

    1. Department of Pharmacology & Therapeutics, FMHS, UAE University, Al Ain, United Arab Emirates
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  • Mohamed Shafiullah,

    1. Department of Pharmacology & Therapeutics, FMHS, UAE University, Al Ain, United Arab Emirates
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  • Mohamed Y. Hasan,

    1. Department of Pharmacology & Therapeutics, FMHS, UAE University, Al Ain, United Arab Emirates
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  • Kamil Kuča,

    1. University of Defense Faculty of Military Health Sciences, Hradec Kralove, Czech Republic
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  • Dietrich E. Lorke

    1. Department of Cellular Biology & Pharmacology, Florida International University, Miami, FL, USA
    2. Department of Anatomy, FMHS, UAE University, Al Ain, United Arab Emirates
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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. Copyright © 2012 John Wiley & Sons, Ltd.

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