Estimate of the Lowest Dose of Diazepam Required to Treat Soman-Induced Convulsions in Rhesus Monkeys Pretreated with Pyridostigmine and Treated with Atropine, Pralidoxime Chloride and Diazepam

The purpose of this study was to estimate the minimal dose of intramuscularly administered diazepam to limit soman-induced convulsions in rhesus monkeys pretreated with pyridostigmine and treated with atropine and 2-PAM. Eleven rhesus monkeys were pretreated with four oral doses of pyridostigmine administered at eight-hour intervals before intramuscular administration of 5 LD50 of soman. All of the animals were-treated with atropine and 2-PAM chloride one minute following exposure to soman. Nine of the eleven animals were also treated with varying intramuscular doses of diazepam immediately following the injection of PAM-C1. The clinical course of recovery of soman intoxication was monitored to identify the presence or absence of tonic-clonic convulsive movements. Two soman-exposed animals that received no diazepam convulsed severely and ultimately lapsed into a prolonged coma. In the two animals treated with 50 ug/kg diazepam, convulsions were prevented in one animal but not the other. When four animals were exposed to soman and treated with atropine, 2-PAM and 100 ug/kg of diazepam, brief convulsions occurred in only one of the four animals. A dose of either 150 or 250 ug/kg of diazepam prevented soman induced convulsions in each of the animals tested at this dose. This study confirmed the ability of diazepam to decrease the severity of convulsive movements in pyridostigmine pretreated primates which had been intoxicated with 5 LD50 of soman and treated with atropine, 2-PAM and various doses of diazepam. Within the limitations of the numbers of animals employed, 100 ug/kg is a minimal dose of dizaepam which will prevent tonic-clonic convulsive movements in most pyridsotigmine pretreated, soman exposed, atropine, 2-PAM and diazepam treated rhesus monkeys.