This study evaluated the anticonvulsant effectiveness of midazolam to stop seizures elicited by the nerve agent soman when midazolam was administered by different routes (intramuscular, intranasal or sublingual) at one of two different times after the onset of seizure activity. Guinea pigs previously prepared with cortical electrodes to record brain electroencephalographic activity were pre-treated with pyridostigmine (0.026 mg/kg, intramuscularly) 30 min. before challenge with a seizure-inducing dose of the nerve agent soman (56 μ g/kg, subcutaneously), and 1 min. later, they were administered 2.0 mg/kg atropine sulfate admixed with 25.0 mg/kg 2-PAM Cl (intramuscularly). Groups of animals were administered differing doses of midazolam by the intramuscular, intranasal or sublingual route at either the onset of seizure activity or 40 min. after the onset of seizure activity that was detected in the electroencephalographic record. When given immediately after seizure onset, the anticonvulsant ED 50 of intramuscular midazolam was significantly lower than that of intranasal midazolam, which in turn was significantly lower than sublingual midazolam at that time. At the 40-min. treatment delay, the anticonvulsant ED 50 s of intramuscular or intranasal midazolam did not differ and both were significantly lower than the sublingual route. Higher doses of midazolam were required to stop seizures at the 40-min. treatment delay time compared to immediate treatment. The speed of seizure control for intramuscular or intranasal midazolam was the same while sublingual midazolam acted significantly slower. Midazolam was effective in treating soman-induced seizures when given by all three routes, but with differences in potency and speed of action.Nerve agent-induced seizures result from over-stimulation of susceptible brain circuits by abnormally high levels of the excitatory neurotransmitter acetylcholine that rapidly builds up after inhibition of the enzyme acetylcholinesterase by nerve agent [1]. These seizures, unless quickly stopped pharmacologically, rapidly progress to status epilepticus, a state of continuous seizure activity or episodes of seizure activity for greater than 30 min. with no recovery of consciousness between episodes. Status epilepticus itself is considered a medical emergency, and the longer seizures persist, the more difficult they are to stop pharmacologically [2]. Status epilepticus clinically responds (n.b. termination of seizures) only to a subset of anticonvulsant or antiepileptic drugs. Benzodiazepines are typically the most effective class of compounds and are used as the first drug of choice in treatment of this condition. Nerve agent-induced status epilepticus also responds to benzodiazepines [3,4], as well as to anticholinergic compounds [5] that have no therapeutic benefit in the treatment of epilepsy or seizures induced by clinical states other than nerve agents.The benzodiazepine diazepam is currently available in auto-injectors as an immediate field treatment to counteract nerve a...

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