Referenced in: none

Automatically associated channels: ClC2 , ClC4

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

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

Journal, date & volume: , 2007 Jan , 8, 66-70

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/17263187

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.