A Comparison of the Neuroprotective and Reactivating Efficacy of a Novel Bispyridinium Oxime K870 with Commonly Used Pralidoxime and the Oxime HI-6 in Tabun-Poisoned Rats

Acta Medica (Hradec Kralove). 2021;64(3):145-152. doi: 10.14712/18059694.2021.25.

Abstract

Aim: The comparison of neuroprotective and central reactivating effects of the oxime K870 in combination with atropine with the efficacy of standard antidotal treatment in tabun-poisoned rats.

Methods: The neuroprotective effects of antidotal treatment were determined in rats poisoned with tabun at a sublethal dose using a functional observational battery 2 h and 24 h after tabun administration, the tabun-induced brain damage was investigated by the histopathological evaluation and central reactivating effects of oximes was evaluated by the determination of acetylcholinesterase activity in the brain using a standard spectrophotometric method.

Results: The central reactivating efficacy of a newly developed oxime K870 roughly corresponds to the central reactivating efficacy of pralidoxime while the ability of the oxime HI-6 to reactivate tabun-inhibited acetylcholinesterase in the brain was negligible. The ability of the oxime K870 to decrease tabun-induced acute neurotoxicity was slightly higher than that of pralidoxime and similar to the oxime HI-6. These results roughly correspond to the histopathological evaluation of tabun-induced brain damage.

Conclusion: The newly synthesized oxime K870 is not a suitable replacement for commonly used oximes in the antidotal treatment of acute tabun poisonings because its neuroprotective efficacy is only slightly higher or similar compared to studied currently used oximes.

Keywords: acetylcholinesterase; functional observational battery; histopathology; neurotoxicity; oximes; rats; tabun.

MeSH terms

  • Acetylcholinesterase
  • Animals
  • Antidotes / pharmacology
  • Chemical Warfare Agents* / toxicity
  • Cholinesterase Inhibitors / pharmacology
  • Cholinesterase Reactivators* / pharmacology
  • Organophosphates*
  • Oximes* / pharmacology
  • Poisons*
  • Pralidoxime Compounds
  • Pyridinium Compounds* / pharmacology
  • Rats
  • Rats, Wistar

Substances

  • Antidotes
  • Chemical Warfare Agents
  • Cholinesterase Inhibitors
  • Cholinesterase Reactivators
  • Organophosphates
  • Oximes
  • Poisons
  • Pralidoxime Compounds
  • Pyridinium Compounds
  • Acetylcholinesterase
  • asoxime chloride
  • pralidoxime
  • tabun