Validating a model of benzodiazepine refractory nerve agent-induced status epilepticus by evaluating the anticonvulsant and neuroprotective effects of scopolamine, memantine, and phenobarbital.

Journal of Pharmacological and Toxicological Methods
Cecelia JacksonHilary S McCarren

Abstract

Organophosphorus nerve agents (OPNAs) irreversibly block acetylcholinesterase activity, resulting in accumulation of excess acetylcholine at neural synapses, which can lead to a state of prolonged seizures known as status epilepticus (SE). Benzodiazepines, the current standard of care for SE, become less effective as latency to treatment increases. In a mass civilian OPNA exposure, concurrent trauma and limited resources would likely cause a delay in first response time. To address this issue, we have developed a rat model to test novel anticonvulsant/ neuroprotectant adjuncts at delayed time points. For model development, adult male rats with cortical electroencephalographic (EEG) electrodes were exposed to soman and administered saline along with atropine, 2-PAM, and midazolam 5, 20, or 40 min after SE onset. We validated our model using three drugs: scopolamine, memantine, and phenobarbital. Using the same procedure outlined above, rats were given atropine, 2-PAM, midazolam and test treatment 20 min after SE onset. Using gamma power, delta power, and spike rate to quantify EEG activity, we found that scopolamine was effective, memantine was minimally effective, and phenobarbital had a delayed effect on terminating SE. Fluoro...Continue Reading

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Citations

Sep 3, 2020·The Journal of Pharmacology and Experimental Therapeutics·Jay SpampanatoF Edward Dudek
Apr 1, 2021·Toxicology and Applied Pharmacology·E WigenstamL Thors
Apr 9, 2021·Chemico-biological Interactions·Miloš P StojiljkovićMatej Maksimović
Jul 18, 2021·Toxicology and Applied Pharmacology·Alex S CornelissenMarloes J A Joosen

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