Optimal Pre-treatment for Acute Exposure to the Organophosphate Dicrotophos

Title:Optimal Pre-treatment for Acute Exposure to the Organophosphate Dicrotophos

Volume: 23 Issue: 23

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

Affiliation:

• Department of Cellular Biology & Pharmacology, Herbert Wertheim College of Medicine, Florida International University, University Park GL 495 D, 11200 SW 8th St, Miami 33199, Florida,United States

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

Abstract: 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.

Cite this article as:

Lorke E. Dietrich*, Nurulain M. Syed, Hasan Y. Mohamed, Kuca Kamil and Petroianu A. Georg, Optimal Pre-treatment for Acute Exposure to the Organophosphate Dicrotophos, Current Pharmaceutical Design 2017; 23 (23) . https://dx.doi.org/10.2174/1381612822666161027154303