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. 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. 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.

中文翻译：

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新型肟逆转低剂量二乙基对氧磷诱导的大鼠通气效应的安全性和有效性

背景：肟与阿托品一起用于治疗有机磷中毒。然而，肟的效率仍然是一个有争议的问题。体外实验表明，新的肟比商业肟更有效。然而，尚未在体内评估新肟的解毒活性。方法：这项工作的目的是在二乙基对氧磷诱导的非致死性呼吸毒性大鼠模型中评估新肟与解磷定相比的安全性和有效性。结果：肟的安全性研究显示对大鼠通气无不良影响。KO-33、KO-48、KO-74 肟在体内没有表现出显着的解毒作用。相比之下，KO-27 和 BI-6 通过呼吸频率和呼吸时间的正常化显示出解毒活性的证据。KO-27 仅在研究的最后 30 分钟内变得效率低下。相比之下，解磷定在注射后 30 分钟时被证明是低效的。相反，BI-6 的解毒活性最近发生在注射后的最后 90 分钟内。结论：这项研究显示了新肟的呼吸安全性。就效率而言，KO-27 显示出是对二乙基对氧磷引起的呼吸毒性的快速解毒剂，而 BI-6 是后效解毒剂。同时给药这两种肟可能会产生完全和延长的解毒效果。就效率而言，KO-27 显示出是对二乙基对氧磷引起的呼吸毒性的快速解毒剂，而 BI-6 是一种迟发性解毒剂。同时给药这两种肟可能会产生完全和延长的解毒效果。就效率而言，KO-27 显示出是对二乙基对氧磷引起的呼吸毒性的快速解毒剂，而 BI-6 是一种迟发性解毒剂。同时给药这两种肟可能会产生完全和延长的解毒效果。