Comparative effects of diazepam and midazolam on paraoxon toxicity in rats

The present study was undertaken to compare the effectiveness of a new water-soluble benzodiazepine, midazolam, to diazepam, both administered im for protection against diethyl-p-nitrophenyl phosphate (paraoxon) toxicity. Adult male Sprague-Dawley rats were pretreated with midazolam or diazepam (0.32-32.0 mg/kg) alone or in combination with atropine (10.0 mg/kg). Twenty minutes later 2 X LD50 of paraoxon was injected sc and the incidence of seizures and death were recorded for 24 hr. In another series of experiments, the LD50 of paraoxon was evaluated in the rats pretreated im with atropine (10.0 mg/kg) and midazolam or diazepam (10.0 mg/kg). Pretreatment with atropine alone did not prevent paraoxon-induced seizures but did reduce mortality. Both benzodiazepines were very effective alone or when combined with atropine in reducing the incidence of paraoxon-induced seizures. When given alone, neither benzodiazepine protected against paraoxon-induced mortality. However, when combined with atropine both benzodiazepines dramatically decreased the lethality of 2 X LD50 of paraoxon. In equal doses given im, midazolam proved to be more potent than diazepam.