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

Article Details

Citation

Crowell MD, Harris LA, DiBaise JK, Olden KW

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

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

PubMed ID
17263187 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Drugs
Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
LubiprostoneChloride channel protein 2ProteinHumans
Yes
Inducer
Details