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Why do benzodiazepines work less well the longer a seizure goes on? A seizure lasting 5 minutes or more should be treated with a benzodiazepine, such as diazepam or midazolam. The timing has a mechanism underneath it. GABA is the brain's main inhibitory neurotransmitter. It acts on GABA-A receptors, opening a chloride channel that moves the neuron further from its firing threshold. Benzodiazepines bind a separate site on the same receptor and increase how often the channel opens, strengthening G
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