Dose Dependent Prophylactic Efficacy of 6-Chlorotacrine in Soman-Poisoned Mice

Acta Medica (Hradec Kralove). 2017;60(4):140-145. doi: 10.14712/18059694.2018.9.

Abstract

Aim: The influence of the dose on the ability of promising newly prepared reversible inhibitor of acetylcholinesterase (6-chlorotacrine) to increase the resistance of mice against soman and the efficacy of antidotal treatment of soman-poisoned mice was evaluated.

Methods: The evaluation of the effect of pharmacological pretreatment is based on the identification of changes of soman-induced toxicity that was evaluated by the assessment of its LD50 value and its 95% confidence limit using probit-logarithmical analysis of death occurring within 24 hrs after administration of soman.

Results: The dose of 6-chlorotacrine significantly influences the prophylactic efficacy of 6-chlorotacrine. Its highest dose was only able to significantly protect mice against acute toxicity of soman and increase the efficacy of antidotal treatment (atropine in combination with the oxime HI-6) of soman-poisoned mice. In addition, the highest dose of 6-chlorotacrine was significantly more effective to protect mice from soman poisoning than its lowest dose.

Conclusion: These findings demonstrate the important influence of the dose of 6-chlorotacine on its prophylactic efficacy in the case of pharmacological pretreatment of soman poisoning in mice.

Keywords: 6-chlorotacrine; HI‑6; atropine; mice; pharmacological pretreatment; soman.

MeSH terms

  • Animals
  • Antidotes / pharmacology
  • Chemically-Induced Disorders / prevention & control*
  • Cholinesterase Inhibitors / poisoning
  • Cholinesterase Reactivators / pharmacology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Mice
  • Pre-Exposure Prophylaxis / methods*
  • Soman / poisoning*
  • Tacrine / analogs & derivatives*
  • Tacrine / pharmacology

Substances

  • 6-chlorotacrine
  • Antidotes
  • Cholinesterase Inhibitors
  • Cholinesterase Reactivators
  • Tacrine
  • Soman