NKCC1 Chloride Importer Antagonists Attenuate Many Neurological and Psychiatric Disorders

Trends Neurosci. 2017 Sep;40(9):536-554. doi: 10.1016/j.tins.2017.07.001. Epub 2017 Aug 14.

Abstract

In physiological conditions, adult neurons have low intracellular Cl- [(Cl-)I] levels underlying the γ-aminobutyric acid (GABA)ergic inhibitory drive. In contrast, neurons have high (Cl-)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 (Cl-)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.

Keywords: GABA; NKCC1 chloride importer; bumetanide; neurological disorders; psychiatric disorders.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bumetanide / adverse effects
  • Bumetanide / pharmacology*
  • Bumetanide / therapeutic use*
  • Humans
  • Mental Disorders / drug therapy*
  • Mental Disorders / metabolism
  • Nervous System Diseases / drug therapy*
  • Nervous System Diseases / metabolism
  • Sodium Potassium Chloride Symporter Inhibitors / adverse effects
  • Sodium Potassium Chloride Symporter Inhibitors / pharmacology*
  • Sodium Potassium Chloride Symporter Inhibitors / therapeutic use*
  • Solute Carrier Family 12, Member 2 / metabolism

Substances

  • Sodium Potassium Chloride Symporter Inhibitors
  • Solute Carrier Family 12, Member 2
  • Bumetanide