PubMed · 687915
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J M Cushnie, D I Ben-Tovim, P Kopelman. 1978-07-29. Chlormethiazole addiction: unusual presentation.. https://doi.org/10.1136/bmj.2.6133.355
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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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An improved high-performance liquid chromatographic method for the determination of chlormethiazole levels in plasma is described. The drug is extracted from plasma using commercially available reversed-phase extraction columns; recovery values obtained using Sep-Pak C18 and Bond Elut C1, C2, C4, C6, C8, C18 columns are compared. Separation was achieved by reversed-phase chromatography, using a mobile phase consisting of 0.025 M sodium acetate buffer, pH 4.5-acetonitrile (67:33) at a flow-rate of 1.6 ml/min in conjunction with a 15-cm Jones Chromatography Apex ODS column. The analytical column was protected by a Waters Assoc. Guard-Pak module containing a Guard-Pak CN insert. Using ultraviolet detection at 254 nm chlormethiazole levels in the region of 50 ng/ml can be measured with only 500 microliter of plasma.