Activation of type-2 chloride channels: A novel therapeutic target for the treatment of chronic constipation

Michael D. Crowell, Lucinda A. Harris, John K. DiBaise, Kevin W. Olden

Research output: Contribution to journalReview article

26 Scopus citations

Abstract

Chronic constipation affects up to 27% of the population and negatively impacts health-related quality-of-life. Prescription medications targeting chronic constipation currently include polyethylene glycol, lactulose and tegaserod, a serotonin type 4 receptor partial agonist. The most recent addition is lubiprostone (Amitiza), a type-2 chloride channel (ClC-2) activator which is a member of a new class of compounds known as prostones. Lubiprostone is a bicyclic fatty acid that acts locally on ClC-2 channels located in the apical membrane of intestinal epithelial cells. This stimulation of chloride secretion induces the passive movement of sodium and water into the intestinal lumen, yielding a net increase in isotonic fluid, which results in improved bowel function. In double-blind, placebo-controlled clinical trials, lubiprostone increased the number of spontaneous bowel movements compared with placebo and was generally well tolerated. The predominant adverse effects were nausea and diarrhea. Lubiprostone represents a new therapeutic class of compounds for the treatment of chronic constipation and will be the focus of this review.

Original languageEnglish (US)
Pages (from-to)66-70
Number of pages5
JournalCurrent Opinion in Investigational Drugs
Volume8
Issue number1
StatePublished - Jan 1 2007

Keywords

  • Chloride channel
  • Clinical trial
  • Constipation
  • Lubiprostone
  • Type-2 chloride channel

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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