Emerging pharmacologic therapies for irritable bowel syndrome.
New therapies are being developed for irritable bowel syndrome (IBS). These advances are based on understanding pathophysiology or the development of medications with greater selectivity in classes of agents with known efficacy. Prucalopride, the newest European Medicines Agency-approved 5-hydroxytryptamine receptor 4 (5-HT(4)) agonist, is effective in the treatment of chronic constipation with improved cardiovascular safety relative to older 5-HT(4) drugs; similarly, ramosetron, the 5-hydroxytryptamine receptor 3 (5-HT(3)) antagonist, appears efficacious in diarrhea-predominant IBS. Secretagogues with different mechanisms of action target apical domains in enterocytes that are involved in chloride secretion, such as chloride channels, the cystic fibrosis transmembrane regulator, and guanylate cyclase C. As a class, such secretagogues have high efficacy and safety for constipation. With more data obtained from phase 2 and 3 trials, we expect other classes of medications, including bile acid modulators, anti-inflammatory agents, visceral analgesics, and newer centrally acting agents to be efficacious and enter the armamentarium for the treatment of IBS in the future.
Manabe
Noriaki
N
Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Mayo Clinic, Charlton 8-110, 200 First Street SW, Rochester, MN 55905, USA.
Rao
Archana S
AS
Wong
Banny S
BS
Camilleri
Michael
M
D000527:Alprostadil / Q000031:analogs & derivatives / Q000494:pharmacology; D000700:Analgesics / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001569:Benzodiazepines / Q000627:therapeutic use; D001647:Bile Acids and Salts / Q000627:therapeutic use; D018118:Chloride Channels / Q000187:drug effects; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000037:antagonists & inhibitors; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D006801:Humans; D007419:Intestinal Secretions / Q000187:drug effects; D043183:Irritable Bowel Syndrome / Q000188:drug therapy*; D000068238:Lubiprostone; D010455:Peptides / Q000494:pharmacology; D044945:Proanthocyanidins / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000627:therapeutic use; D017366:Serotonin Receptor Agonists / Q000627:therapeutic use
D000700:Analgesics; D000893:Anti-Inflammatory Agents; D001647:Bile Acids and Salts; D018118:Chloride Channels; D005765:Gastrointestinal Agents; D010455:Peptides; D044945:Proanthocyanidins; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D001569:Benzodiazepines; D000068238:Lubiprostone; D000527:Alprostadil; C523483:linaclotide; C546704:crofelemer; C012582:tofisopam