Irritable Bowel Syndrome (cont.)

The future of IBS depends on our increasing knowledge of the processes (mechanisms) that cause IBS. Acquiring this knowledge, in turn, depends on research funding. Because of the difficulties in conducting research in IBS, this knowledge will not come quickly. Until we have an understanding of the mechanisms of IBS, newer treatments will be based on our developing understanding of the normal control of gastrointestinal function, which is proceeding more rapidly. Specifically, there is intense interest in intestinal neurotransmitters, which are chemicals that the nerves of the intestine use to communicate with each other. The interactions of these neurotransmitters are responsible for adjusting (modulating) the functions of the intestines, such as contraction of muscles and secretion of fluid and mucus.

5-hydroxytriptamine (5-HT or serotonin) is a neurotransmitter that stimulates several different receptors on nerves in the intestine, including one called the 5-HT4 receptor. Stimulation of these receptors by 5-HT increases muscle contractions in the colon. An example of an experimental drug that affects intestinal neurotransmission is tegaserod. This drug mimics the effect of 5-HT on the 5-HT4 receptor. Thus, because it increases intestinal muscle contractions, tegaserod is being tested for effectiveness in treating constipation-predominant IBS as well as constipation in general.

Another drug that affects neurotransmission is ondansetron. This drug blocks a different receptor, the 5-HT3 receptor, and thereby reduces colonic contractions. Thus, ondansetron (Zofran) has been effective in treating diarrhea-predominant IBS in initial studies. There are drugs that stimulate another receptor, the 5-HT1 receptor. Examples of this type of drug are sumatriptan (Imitrex) and buspirone (Buspar). These drugs are believed to reduce the responsiveness (sensitivity) of the sensory nerves to what's happening in the intestine. The 5-HT1 receptor stimulators, however, have not yet been tested for effectiveness in IBS. In preliminary studies, fedotozine has been shown to improve functional gastrointestinal symptoms. The mechanism of action of fedotozine is not known, but it also may act by reducing the sensitivity of the sensory nerves.

Finally, there is the issue of a relationship between IBS and intestinal bacteria. Over the next few years, much information will accumulate on this potential relationship.

REFERENCE:

Drossman, D. A. et al. AGA technical review on irritable bowel syndrome. Gastroenterology 2002;123:2108-2131

Pimentel et al. Rifaximin Therapy for Patients with Irritable Bowel Syndrome without Constipation. N Engl J Med 2011;364:22-32.

Previous contributing editors: Leslie J. Schoenfield, MD, PhD and Dennis Lee, MD

Source: MedicineNet.com
http://www.medicinenet.com/irritable_bowel_syndrome/article.htm