Optimal Pre-treatment for Acute Exposure to the Organophosphate Dicrotophos

Author(s): Dietrich E. Lorke*, Syed M. Nurulain, Mohamed Y. Hasan, Kamil Kuca, Georg A. Petroianu

Journal Name: Current Pharmaceutical Design

Volume 23 , Issue 23 , 2017

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Background: Reversible cholinesterase inhibitors, when given prophylactically before exposure to organophosphates, are able to decrease organophosphate-induced mortality. However, the efficacy of pyridostigmine, the only pre-treatment substance approved by the US Federal Drug Administration, is unsatisfactory.

Methods: In search of a better prophylactic compound, we determined in vivo the protection conferred by five cholinesterase inhibitors (ranitidine, physostigmine, tacrine, K-27 and pyridostigmine), which were administered in equitoxic dosage (1/4 of LD01) 30 minutes before exposure to the organophosphate dicrotophos. Efficacy was measured in rats by Cox analysis calculating the relative risk of death (RR), RR being 1 for the reference group which received dicrotophos and no prophylaxis.

Results: K-27 (RR=0.06), physostigmine (RR=0.15), pyridostigmine (RR=0.22) and tacrine (RR=0.28) significantly (p ≤ 0.05) reduced dicrotophos-induced mortality in comparison to the reference group (dicrotophos without pre-treatment), whereas ranitidine (RR=0.86) had no significant influence. The experimental oxime K-27, when given before dicrotophos exposure, conferred the best in vivo protection. This was significantly (p ≤ 0.05) more efficacious than pre-treatment with any other tested compound. The differences in efficacy between the second best compound, physostigmine, and the less efficacious substances (tacrine and pyridostigmine) were also statistically significant.

Conclusion: These data indicate that K-27 can be considered a very efficacious prophylactic agent for organophosphate exposure.

Keywords: Carbamates, cholinesterase, cox analysis, dicrotophos, organophosphate, prophylaxis, rat.

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Article Details

Year: 2017
Published on: 27 September, 2017
Page: [3432 - 3439]
Pages: 8
DOI: 10.2174/1381612822666161027154303
Price: $65

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