Neuroprotective agents inhibit reactions in the brain ischaemic injury cascade which lead to neuronal death. Gamma-aminobutyric acid (GABA) is a naturally occurring inhibitory neurotransmitter that increases chloride influx into the neuron and counteracts the toxic effects of glutamate. Clomethiazole is a GABA(A) agonist, which causes membrane hyperpolarization, counteracting depolarization and the subsequent cascade of biochemical events that result in neuronal death. Promising results in animal models resulted in clinical trials conducted in humans. However, large randomized placebo controlled trials in Europe, Canada and North America did not show the superiority of clomethiazole over placebo that was seen in animal models.
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