Chloride channels as drug targets

Alan S. Verkman, Luis J V Galietta

Research output: Contribution to journalArticle

Abstract

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 GABAA (γ-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.

Original languageEnglish
Pages (from-to)153-171
Number of pages19
JournalNature Reviews Drug Discovery
Volume8
Issue number2
DOIs
Publication statusPublished - 2009

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology

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    Verkman, A. S., & Galietta, L. J. V. (2009). Chloride channels as drug targets. Nature Reviews Drug Discovery, 8(2), 153-171. https://doi.org/10.1038/nrd2780