Safety and Efficacy of New Oximes to Reverse Low Dose Diethyl-Paraoxon-Induced Ventilatory Effects in Rats

新肟类药物逆转大鼠低剂量二乙基对氧磷诱发通气效应的安全性和有效性

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作者:Maya Kayouka, Pascal Houzé, Marc Lejay, Frederic J Baud, Kamil Kuca

Background

Oximes are used in addition to atropine to treat organophosphate poisoning. However, the efficiency of oximes is still a matter of debate. In vitro experiments suggested than new oximes are more potent than the commercial oximes. However, the antidotal activity of new oximes has not been assessed in vivo.

Conclusion

This study showed respiratory safety of new oximes. Regarding, the efficiency, KO-27 revealed to be a rapid acting antidote toward diethylparaoxon-induced respiratory toxicity, meanwhile BI-6 was a late-acting antidote. Simultaneous administration of these two oximes might result in a complete and prolonged antidotal efficiency.

Methods

The aim of this work was to assess the safety and efficiency of new oximes compared to pralidoxime in a rat model of diethyl paraoxon-induced non-lethal respiratory toxicity.

Results

Safety study of oximes showed no adverse effects on ventilation in rats. KO-33, KO-48, KO-74 oximes did not exhibit significant antidotal effect in vivo. In contrast, KO-27 and BI-6 showed evidence of antidotal activity by normalization of respiratory frequency and respiratory times. KO-27 became inefficient only during the last 30 min of the study. In contrast, pralidoxime demonstrated to be inefficient at 30 min post injection. Inversely, the antidotal activity of BI-6 occurred lately, within the last 90 min post injection.

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