Irritable bowel syndrome (IBS) is a highly prevalent functional bowel disorder.
Serotonin (5-HT) is known to play a physiological and pathophysiological role in the regulation of gastrointestinal function. In experimental studies,
5-HT3 receptor antagonists have been reported to slow colon transit, to blunt gastrocolonic reflex, and to reduce rectal sensitivity.
Alosetron and
cilansetron, potent and selective
5-HT3 receptor antagonists, have proven efficacy in the treatment of IBS with
diarrhea (IBS-D). However,
alosetron was voluntarily withdrawn due to postmarketing reports of
ischemic colitis and complications of
constipation, and
cilansetron was never marketed. Currently
alosetron is available under a risk management program for women with severe IBS-D.
Ramosetron is another potent and selective
5-HT3 receptor antagonist, which has been marketed in Japan, South Korea, and Taiwan. In animal studies,
ramosetron reduced defecation induced by
corticotrophin-releasing
hormone and had inhibitory effects on colonic nociception. In two randomized controlled studies including 957 patients with IBS-D,
ramosetron increased monthly responder rates of patient-reported global assessment of IBS symptom relief compared with placebo.
Ramosetron was also as effective as
mebeverine in male patients with IBS-D. In a recent randomized controlled trial with 343 male patients with IBS-D,
ramosetron has proved effective in improving stool consistency, relieving
abdominal pain/discomfort, and improving health-related quality of life. Regarding safety,
ramosetron is associated with a lower incidence of
constipation compared with other
5-HT3 receptor antagonists and has not been associated with
ischemic colitis. Although further large prospective studies are needed to assess whether
ramosetron is effective for female patients with IBS-D and to evaluate its long-term safety,
ramosetron appears to be one of the most promising agents for patients with IBS-D.