Prophylactic administration of non-organophosphate cholinesterase inhibitors before acute exposure to organophosphates: assessment using terbufos sulfone

Authors

  • Dietrich E. Lorke,

    1. Department of Cellular Biology & Pharmacology, Florida International University, Miami, Florida, USA
    2. Department of Anatomy, FMHS, UAE University, Al Ain, United Arab Emirates
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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 Y. Hasan,

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

    1. Biomedical Research Center, University Hospital, Hradec Kralove, Czech Republic
    2. Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Czech Republic
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  • Georg A. Petroianu

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

      Email: georg.petroianu@fiu.edu

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ABSTRACT

Poisoning with organophosphorus compounds (OPCs) poses a serious threat worldwide. OPC-induced mortality can be significantly reduced by prophylactic administration of reversible acetylcholinesterase (AChE) inhibitors. The only American Food and Drug Administration (FDA)-approved substance for such pre-treatment (to soman exposure) is presently pyridostigmine, although its efficacy is controversial. In search for more efficacious and broad-spectrum alternatives, we have assessed in vivo the mortality-reducing efficacy of a group of five compounds with known AChE inhibitory activity (pyridostigmine, physostigmine, ranitidine, tacrine and K-27), when given in equitoxic dosage (25% of LD01) 30 min before exposure to the OPC terbufos sulfone. Protection was quantified in rats by determining the relative risk of death (RR) using Cox analysis, with RR = 1 for animals given only terbufos sulfone, but no pre-treatment. All tested AChE inhibitors reduced terbufos sulfone-induced mortality significantly (p ≤ 0.05) as compared with the non-treatment group (RR = 1: terbufos sulfone only). Best in vivo protection from terbufos sulfone-induced mortality was achieved, when K-27 was given before terbufos sulfone exposure (RR = 0.06), which was significantly (P ≤ 0.05) superior to the pre-treatment with all other tested compounds, for example tacrine (RR = 0.21), pyridostigmine (RR = 0.28), physostigmine (RR = 0.29) and ranitidine (RR = 0.33). The differences in efficacy between tacrine, pyridostigmine, physostigmine and ranitidine were not statistically significant. Prophylactic administration of an oxime (such as K-27) in case of imminent OPC exposure may be a viable option. Copyright © 2013 John Wiley & Sons, Ltd.

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