Related Experiment Video
Updated: Oct 17, 2025

Study of the Functions and Activities of Neuronal K-Cl Co-Transporter KCC2 Using Western Blotting
Published on: December 9, 2022
Pharmacological tools to target NKCC1 in brain disorders
Annalisa Savardi1, Marco Borgogno2, Marco De Vivo2
1Brain Development and Disease Laboratory, Istituto Italiano di Tecnologia, via Morego, 30, 16163 Genoa, Italy; Dulbecco Telethon Institute, 00185 Rome, Italy; Molecular Modeling and Drug Discovery Laboratory, Istituto Italiano di Tecnologia, via Morego, 30, 16163 Genoa, Italy.
Abstract:
The chloride importer NKCC1 and the chloride exporter KCC2 are key regulators of neuronal chloride concentration. A defective NKCC1/KCC2 expression ratio is associated with several brain disorders. Preclinical/clinical studies have shown that NKCC1 inhibition by the United States FDA-approved diuretic bumetanide is a potential therapeutic strategy in preclinical/clinical studies of multiple neurological conditions. However, bumetanide has poor brain penetration and causes unwanted diuresis by inhibiting NKCC2 in the kidney. To overcome these issues, a growing number of studies have reported more brain-penetrating and/or selective bumetanide prodrugs, analogs, and new molecular entities. Here, we review the evidence for NKCC1 pharmacological inhibition as an effective strategy to manage neurological disorders. We also discuss the advantages and limitations of bumetanide repurposing and the benefits and risks of new NKCC1 inhibitors as therapeutic agents for brain disorders.
Related Concept Videos
Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists
Cognitive Enhancers: Cholinesterase Inhibitors and NMDA Receptor Antagonists
Non-gated Ion Channels
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism....
Drugs Affecting Neurotransmitter Release or Uptake
Ligand-Gated Ion Channel Receptor: Gating Mechanism
Antiepileptic Drugs: Glutamate Antagonists

