Send to

Choose Destination
Curr Opin Investig Drugs. 2007 Jan;8(1):66-70.

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

Author information

Mayo Clinic Scottsdale, Division of Gastroenterology and Hepatology, 13400 East Shea Blvd, Scottsdale, AZ 85259, USA.


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.

[Indexed for MEDLINE]

Supplemental Content

Loading ...
Support Center