The therapeutic efficacy of oxime treatment in cyclosarin-poisoned mice pretreated with a combination of pyridostigmine benactyzine and trihexyphenidyl

The present study was performed to assess and compare the therapeutic efficacy of various oximes (methoxime, BI-6, HI-6) combined with benactyzine (BNZ) in cyclosarin (GF-agent)-poisoned mice and to evaluate the influence of pretreatment with PANPAL (pyridostigmine, benactyzine and trihexyphenidyl) on the effect of antidotal treatment in mice poisoned with the GF-agent. In the first part of our experiment, methoxime, BI-6 or HI-6 in combination with benactyzine were used for the treatment of GF-poisoned mice. In the second part of the experiment the animals were pretreated with PANPAL 60 min before the GF-agent challenge and then the oxime therapy was applied in the same time scheme as before. All the therapeutic regimens showed a protective ratio higher than 2 and significantly increased the LD50 of GF-agent. The most efficacious oxime in decreasing of GF-agent toxicity was HI-6. PANPAL increased the protective ratios of all therapeutic regimens in comparison with administration of the oxime and BNZ alone. From the results obtained, the combination of pretreatment with PANPAL and following therapy with BNZ and HI-6 seems to be the most efficacious therapeutic regimen for treatment of GF-agent-poisoned mice.