Acta Med. 2017, 60: 37-43
The Evaluation of Benefit of Newly Prepared Reversible Inhibitors of Acetylcholinesterase and Commonly Used Pyridostigmine as Pharmacological Pretreatment of Soman-Poisoned Mice
Aim: The ability of four newly prepared reversible inhibitors of acetylcholinesterase (6-chlorotacrine, 7-phenoxytacrine, compounds 1 and 2) and currently used carbamate pyridostigmine 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 probitlogarithmical analysis of death occurring within 24 h after administration of soman. Results: 6-chlorotacrine was only able to markedly protect mice against acute toxicity of soman. In addition, the pharmacological pretreatment with 6-chlorotacrine or compound 2 was able to increase the efficacy of antidotal treatment (the oxime HI-6 in combination with atropine) of soman-poisoned mice. The other newly prepared reversible inhibitors of acetylcholinesterase (7-phenoxytacrine, compound 1) as well as commonly used pyridostigmine did not influence the efficacy of antidotal treatment. Conclusion: These findings demonstrate that pharmacological pretreatment of somanpoisoned mice can be promising and useful in the case of administration of 6-chlorotacrine and partly compound 2.
Keywords
soman, reversible inhibitors of acetylcholinesterase, antidotes, pharmacological pretreatment, mice.
Funding
The study was funded by the grant of Ministry of Defense of the Czech Republic – “Long-term organization development plan Medical Aspects of Weapons of Mass Destruction of the Faculty of Military Health Sciences, University of Defence”.
References
Copyright
This is an open-access article distributed under the terms of the Creative Commons Attribution License.
