Chloride channels as drug targets

Nat Rev Drug Discov. 2009 Feb;8(2):153-71. doi: 10.1038/nrd2780. Epub 2008 Jan 19.


Chloride channels represent a relatively under-explored target class for drug discovery as elucidation of their identity and physiological roles has lagged behind that of many other drug targets. Chloride channels are involved in a wide range of biological functions, including epithelial fluid secretion, cell-volume regulation, neuroexcitation, smooth-muscle contraction and acidification of intracellular organelles. Mutations in several chloride channels cause human diseases, including cystic fibrosis, macular degeneration, myotonia, kidney stones, renal salt wasting and hyperekplexia. Chloride-channel modulators have potential applications in the treatment of some of these disorders, as well as in secretory diarrhoeas, polycystic kidney disease, osteoporosis and hypertension. Modulators of GABA(A) (gamma-aminobutyric acid A) receptor chloride channels are in clinical use and several small-molecule chloride-channel modulators are in preclinical development and clinical trials. Here, we discuss the broad opportunities that remain in chloride-channel-based drug discovery.

Publication types

  • Review

MeSH terms

  • Chloride Channels / antagonists & inhibitors
  • Chloride Channels / classification
  • Chloride Channels / drug effects
  • Chloride Channels / physiology*
  • Chlorides* / metabolism
  • Chlorides* / physiology
  • Cystic Fibrosis / drug therapy
  • Cystic Fibrosis / metabolism
  • Cystic Fibrosis Transmembrane Conductance Regulator / antagonists & inhibitors*
  • Cystic Fibrosis Transmembrane Conductance Regulator / physiology
  • Drug Delivery Systems / methods*
  • Humans
  • Ion Channel Gating / drug effects
  • Ion Channel Gating / physiology*


  • CFTR protein, human
  • CLCA1 protein, human
  • Chloride Channels
  • Chlorides
  • Cystic Fibrosis Transmembrane Conductance Regulator