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.

Bioactive Molecules Research Laboratory Faculty of Sciences Section 2 Lebanese University Beirut Lebanon

Département d'Anesthésie Réanimation SAMU de Paris Hôpital Universitaire Necker Enfants Malades 75015 Paris France

Department of Chemistry Faculty of Science University of Hradec Kralove Hradec Kralove 50003 Czech Republic

EA 7323 Pharmacologie et évaluations thérapeutiques chez l'enfant et la femme enceinte Université de Paris F 75006 Paris France

Laboratoire de Toxicologie Biologique GH Lariboisière St Louis F Widal Assistance Publique Hôpitaux de Paris 75010 Paris France

Unité de Technologies Chimiques et Biologiques pour la Santé CNRS UMR8258 U1022 Faculté de Pharmacie Paris Descartes Université de Paris 75006 Paris France

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Experimental and Established Oximes as Pretreatment before Acute Exposure to Azinphos-Methyl