The purpose of this study was to compare the efficacy of
diazepam and the
pro-diazepam avizafone in preventing the severity of
soman-induced pathology in guinea pig. Survival, respiration and
seizures of experimental animals were investigated with on-line monitoring of respiratory and EEG parameters. Guinea pigs were pretreated with
pyridostigmine (0.1mg/kg i.m.) and 30 min later challenged with 1 or 2 LD50
soman. One minute after intoxication they were treated with
atropine (3 or 33.8 mg/kg),
pralidoxime chloride (32 mg/kg) and either
diazepam (2 mg/kg),
avizafone (3.5 mg/kg) or
saline solution. The highest dose of
atropine (33.8 mg/kg) gave a protective effect in groups treated without
anticonvulsants by reducing the severity of clinical signs and death within 24 h but also by decreasing seizure occurrence and
brain injuries. When injected at the similar molar dose of 7 micromoles/kg, the protection of
anticonvulsants against
soman neurotoxicity was higher with the
atropine/
pralidoxime/
avizafone combination than with
atropine/
pralidoxime/
diazepam. Indeed, when
atropine was used at the lowest dose,
avizafone was found to prevent early mortality and
seizures occurrence with better efficacy than
diazepam. On the other hand, when added to the
therapy, the both
anticonvulsants did not prevent the moderate EEG depression (reduction of amplitude by 30-52%) observed under 2 LD50
soman. Moreover, the number of animals suffering from respiratory distress (defined as a decrease of minute ventilation of more than 20% from the baseline value) was enhanced when
diazepam or
avizafone were used in the
therapy. This effect was dependent on the
atropine dose and the nature of the
anticonvulsant. The beneficial effects of the different
therapeutics tested were assessed and compared to the previous data obtained with the same
therapies against
sarin and from the pharmacokinetics properties of the
atropine/
diazepam mixture.