Combination anticonvulsant treatment of soman-induced seizures

Journal of Applied Toxicology : JAT
I KoplovitzJ H McDonough

Abstract

These studies investigated the effectiveness of combination treatment with a benzodiazepine and an anticholinergic drug against soman-induced seizures. The anticholinergic drugs considered were biperiden, scopolamine, trihexaphenidyl, and procyclidine; the benzodiazepines were diazepam and midazolam. Male guinea pigs were implanted surgically with cortical screw electrodes. Electrocorticograms were displayed continually and recorded on a computerized electroencephalographic system. Pyridostigmine (0.026 mg x kg(-1), i.m.) was injected as a pretreatment to inhibit red blood cell acetylcholinesterase by 30-40%. Thirty minutes after pyridostigmine, 2 x LD50 (56 microg x kg(-1)) of soman was injected s.c., followed 1 min later by i.m. treatment with atropine (2 mg x kg(-1)) + 2-PAM (25 mg x kg(-1)). Electrographic seizures occurred in all animals. Anticonvulsant treatment combinations were administered i.m. at 5 or 40 min after seizure onset. Treatment consisted of diazepam or midazolam plus one of the above-mentioned anticholinergic drugs. All doses of the treatment compounds exhibited little or no antiseizure efficacy when given individually. The combination of a benzodiazepine and an anticholinergic drug was effective in termina...Continue Reading

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Citations

Aug 6, 2008·Toxicology and Applied Pharmacology·Ben Avi Weissman, Lily Raveh
Aug 24, 2011·Journal of Applied Toxicology : JAT·Yossi RosmanYael Mardor
Apr 23, 2013·CNS Neuroscience & Therapeutics·Frederic DorandeuGuy Testylier
Apr 22, 2003·Annual Review of Biomedical Engineering·Alan J RussellRichard R Koepsel
Jun 4, 2016·Annals of the New York Academy of Sciences·Hilary S McCarren, John H McDonough
Jan 12, 2007·The Neurologist·Jonathan Newmark
Feb 25, 2019·Neurobiology of Disease·Vassiliki Aroniadou-AnderjaskaMaria F Braga

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