Pyridinium oximes: rationale for their selection as causal antidotes against organophosphate poisonings and current solutions for auto-injectors

Arh Hig Rada Toksikol. 2006 Dec;57(4):435-43.

Abstract

During the last five decades, five pyridinium oximes were found to be worthy of use as antidotes against nerve agents in humans: pralidoxime, in a form of chloride or PAM-2 Cl and mesylate or P2S (against sarin, cyclosarin and VX), trimedoxime or TMB-4 and obidoxime or LüH-6 (both against tabun, sarin and VX), HI-6 (against sarin, soman, cyclosarin and VX) and HLö-7 (against all the five nerve agents). In order to provide the auto-injector with the best and most potent acetylcholinesterase reactivator, the Defence Research and Development Canada (DRDC) received in the 1990s a core funding from the federal government's CBRN research and Technology Initiative (CRTI). Its ultimate result should be three products: (1) 3-in-1 auto-injector (atropine, HI-6 dimethanesulphonate and avizafone, as anticonvulsant), (2) 2-in-1 auto-injector (atropine and HI-6 dimethanesulphonate) and (3) HI-6 dimethanesulphonate in a vial for administration by the medically trained personnel. Previous experimental and clinical experience suggests that, among the oximes mentioned, only trimedoxime and obidoxime can be used for acetylcholinesterase reactivation and antidotal protection against most of the organophosphorus insecticides. The search for an "omnipotent" oxime, effective in reactivation of AChE inhibited with both nerve agents and organophosphorus insecticides, is still ongoing.

Publication types

  • Review

MeSH terms

  • Antidotes / therapeutic use*
  • Chemical Warfare Agents / poisoning*
  • Cholinesterase Reactivators / therapeutic use*
  • Humans
  • Injections
  • Organophosphate Poisoning*
  • Oximes / therapeutic use*
  • Pyridinium Compounds / therapeutic use*

Substances

  • Antidotes
  • Chemical Warfare Agents
  • Cholinesterase Reactivators
  • Oximes
  • Pyridinium Compounds