Review article: new receptor targets for medical therapy in irritable bowel syndrome
Article first published online: 24 SEP 2009
© 2010 Blackwell Publishing Ltd
Alimentary Pharmacology & Therapeutics
Volume 31, Issue 1, pages 35–46, January 2010
How to Cite
CAMILLERI, M. (2010), Review article: new receptor targets for medical therapy in irritable bowel syndrome. Alimentary Pharmacology & Therapeutics, 31: 35–46. doi: 10.1111/j.1365-2036.2009.04153.x
- Issue published online: 2 DEC 2009
- Article first published online: 24 SEP 2009
- Publication data Submitted 30 June 2009 First decision 27 July 2009 Resubmitted 17 September 2009 Accepted 18 September 2009 Epub Accepted Article 24 September 2009
Background Despite setbacks to the approval of new medications for the treatment of irritable bowel syndrome, interim guidelines on endpoints for irritable bowel syndrome (IBS) trials have enhanced interest as new targets for medical therapy are proposed based on novel mechanisms or chemical entities.
Aims To review the approved lubiprostone, two targets that are not meeting expectations (tachykinins and corticotrophin-releasing hormone), the efficacy and safety of new 5-HT4 agonists, intestinal secretagogues (chloride channel activators, and guanylate cyclase-C agonists), bile acid modulation, anti-inflammatory agents and visceral analgesics.
Methods Review of selected articles based on PubMed search and clinically relevant information on mechanism of action, safety, pharmacodynamics and efficacy.
Results The spectrum of peripheral targets of medical therapy addresses chiefly the bowel dysfunction of IBS and these effects are associated with pain relief. The pivotal mechanisms responsible for the abdominal pain or visceral sensation in IBS are unknown. The new 5-HT4 agonists are more specific than older agents and show cardiovascular safety to date. Secretory agents have high specificity, low bioavailability and high efficacy. The potential risks of agents ‘borrowed’ from other indications (such as hyperlipidaemia, inflammatory bowel disease or somatic pain) deserve further study.
Conclusions There is reason for optimism in medical treatment of IBS with a spectrum of agents to treat bowel dysfunction. However, visceral analgesic treatments are still suboptimal.