Optimal Pre-treatment for Acute Exposure to the Organophosphate Dicrotophos.

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.

journal_name

Curr Pharm Des

authors

Lorke DE,Nurulain SM,Hasan MY,Kuca K,Petroianu GA

doi

10.2174/1381612822666161027154303

subject

Has Abstract

pub_date

2017-01-01 00:00:00

pages

3432-3439

issue

23

eissn

1381-6128

issn

1873-4286

pii

CPD-EPUB-79334

journal_volume

23

pub_type

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