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

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.