Efficacy of Several Oximes on Organophosphorus Poisoning

Abstract

Various organophosphorus compounds, particularly those with low acute toxicity levels, such as Fenitrothion (common name; Sumithion), Fenthion (common name; Baycid) and Pyridaphenthion (common name; Ofunack), are widely used as insecticides around the world. PAM (2-Pyridinum aldoxime methiodide), the specific antidote against Parathion, is not very effective against poisoning by these organophosphates.
This paper reports on the efficacy of PAM and other oximes (Pro-PAM, Toxogonin, TMB-4, and PAD) on toxic symptoms and inhibition of ChE (Cholinesterase) by organophosphates (Dichlorvos, Fenthion, Fenitrothion and Pyridaphenthion). The results were as follows.
1. PAD, a high lipid soluble oxime, was not suitable as an antidote against organophosphorus poisoning because it caused irritation and had its own high toxicity.
2. TMB-4 reactivated blood ChE inhibited by organophosphates to the same level as PAM. But the oxime is no practical use as an antagonist because of high toxicity.
3. Pro-PAM, the prodrug of PAM, and Toxogonin, which has been used practically in Germany, could lighten the toxic symptoms of organophosphorus poisoning to the same level as PAM. The efficacy of these oximes was maintained for 2-3hrs.
4. Pro-PAM, Toxogonin and PAM were able to reactivate blood ChE inhibited by Pyridaphenthion and Fenitrothion, but these oximes couldn't reactivate ChE in brain and other tissues.
5. There was no difference in the antidotal action of PAM, Pro-PAM and Toxogonin because of the same reactivation level of blood ChE and the same recovery pattern of serum ChE isoenzyme.
Therefore, it became clear that Pro-PAM and Toxogonin were not more effective against organophosphorus poisoning than PAM. It seemed that a continuous dose of PAM was more effective, and furthermore, that the antidotal effect of PAM should be potentiated by atropine and other therapy.