title: Comparison of the intramuscular, intranasal or sublingual routes of midazolam administration for the control of soman-induced seizures.
abstract: 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 microg/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 ED50 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 ED50s 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.
authors.affiliation: Pharmacology Branch, Research Division, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD, USA. john.mcdonough1@us.army.mil
authors.forename: John H
authors.initials: JH
authors.lastname: McDonough
authors.forename: Kerry E
authors.initials: KE
authors.lastname: Van Shura
authors.forename: John C
authors.initials: JC
authors.lastname: LaMont
authors.forename: Joseph D
authors.initials: JD
authors.lastname: McMonagle
authors.forename: Tsung-Ming
authors.initials: TM
authors.lastname: Shih
mesh_terms: D000281:Administration, Intranasal; D000286:Administration, Sublingual; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000627:therapeutic use; D002619:Chemical Warfare Agents / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D007273:Injections, Intramuscular; D008297:Male; D008874:Midazolam / Q000008:administration & dosage* / Q000627:therapeutic use; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*; D012999:Soman / Q000633:toxicity*
chemical_list: D000927:Anticonvulsants; D002619:Chemical Warfare Agents; D012999:Soman; D008874:Midazolam