Irritable bowel syndrome (IBS) is a functional disease with persisting gastrointestinal symptoms that has been classified into four subtypes.
Serotonin (
5-hydroxytryptamine [5-HT]) plays important physiological roles in the contraction and relaxation of smooth muscle. Intraluminal distension of the intestine is known to stimulate the release of endogenous
5-HT from enterochromaffin cells, activating 5-HT3 receptors located on primary afferent neurons and leading to increases in intestinal secretions and peristaltic activity.
Ramosetron, a potent and selective 5-HT3-receptor antagonist, has been in development for use in patients suffering from
diarrhea-predominant IBS. In a double-blind, placebo-controlled, parallel-group study of 418 patients with
diarrhea-predominant IBS-D, once-daily 5 μg and 10 μg doses of
ramosetron increased the monthly responder rates of IBS symptoms compared to placebo. In a 12-week randomized controlled trial of 539 patients, a positive response to treatment was reported by 47% of a once-daily 5 μg dose of
ramosetron-treated individuals compared to 27% of patients receiving placebo (P<0.001). Furthermore, the responder rate was increased in the
oral administration of 5 μg of
ramosetron for at least 28 weeks (up to 52 weeks), and long-term efficacy for overall improvement of IBS symptoms was also demonstrated. The rate was further increased subsequently. Adverse events were reported by 7% in
ramosetron treatment. No serious adverse events, eg, severe
constipation or
ischemic colitis, were reported for long-term treatment with
ramosetron. In conclusion, further studies to evaluate the long-term efficacy and safety of
ramosetron are warranted in the form of randomized controlled trials.