Abstract
AbstractBenzodiazepines (BZDs) such as Zolpidem can produce a temporary revival of patients who have been akinetic and apathic for years. The mechanisms underlying this “awakening” reaction are suggested globally to be related to an activation of gamma-aminobutyric acid (GABA) inhibitory systems. However, brain trauma or cerebro-vascular infarcts, like many other pathological insults, are associated with a shift of the polarity of GABA from inhibition to excitation consequently to an increase of intracellular chloride concentration ([Cl−]i) levels. Experimental and clinical observations suggest that BZDs generate paradoxical reactions in these conditions, hence the transient “awakening”. The NKCC1 (Na-K-2Cl co-transporter isoform 1) chloride importer antagonist Bumetanide restores low [Cl−]i levels and an efficient inhibitory drive. It is therefore suggested that the administration of Bumetanide might provide a persistent “awakening” by shifting GABAergic actions from excitation to inhibition and attenuating the mechanism underlying the apathic/akinetic state.
Publisher
Springer Science and Business Media LLC
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