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

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.