NKCC1 chloride importer antagonists attenuate many neurological and psychiatric disorders
Yehezkel Ben-Ari, Review Trends in Neurosciences August 2017
High levels of chloride are found in many neurological and psychiatric disorders leading to reduced efficacy of neuronal inhibition. Hence the idea to reduce these levels with specific drugs. The diuretic bumetanide that efficiently reduces chloride has shown efficacy in both experimental and clinical conditions. This review summarizes the promises of bumetanide to treat many disorders.
Abstract
In physiological conditions, adult neurons have low intracellular Cl2 [(Cl2)I] levels underlying the g-aminobutyric acid (GABA)ergic inhibitory drive. In contrast, neurons have high (Cl2)I levels and excitatory GABA actions in a wide range of pathological conditions including spinal cord lesions, chronic pain, brain trauma, cerebrovascular infarcts, autism, Rett and Down syndrome, various types of epilepsies, and other genetic or environmental insults. The diuretic highly specific NKCC1 chloride importer antagonist bumetanide (PubChem CID: 2461) efficiently restores low (Cl2)I levels and attenuates many disorders in experimental conditions and in some clinical trials. Here, I review the mechanisms of action, therapeutic effects, promises, and pitfalls of bumetanide.
