Tegaserod for Constipation‐Predominant Irritable Bowel Syndrome

Abstract

Tegaserod, a selective and partial agonist at the 5-hydroxytryptamine (5-HT [serotonin]) receptor subtype 4 (5-HT4), is the only United States Food and Drug Administration-approved drug for the treatment of constipation-predominant irritable bowel syndrome (IBS) in women. The drug's stimulation of 5-HT4 receptors on intestinal enterocytes increases peristaltic activity and fluid secretion into the gut lumen, facilitating stool passage. In addition, affinity of tegaserod for 5-HT4 receptors modulates visceral sensitivity, which helps alleviate abdominal pain associated with constipation-predominant IBS. The drug's pharmacokinetic and pharmacodynamic parameters do not differ significantly with age or sex. Tegaserod safely and effectively relieves overall gastrointestinal symptoms and abdominal discomfort and normalizes bowel habits in patients with constipation-predominant IBS. It is associated with few drug interactions. In clinical studies, tegaserod was well tolerated, and its adverse-effect profile was similar to that of placebo. Severe diarrhea, as well as abdominal pain, flatulence, headache, and nausea, were the most commonly reported events. Patients who experience severe diarrhea should discontinue the drug. With the data available, tegaserod remains an option for patients with constipation-predominant IBS.

Serotonin Receptors

“…418,419 For treatment of IBS with constipation, 5-HT 4 receptor agonists, as discussed earlier, can be effective. 246 Expression of the 5-HT 3 receptor in forebrain areas indicates that this receptor may play a role in higher cognitive processes, and receptor antagonists might be useful in treating schizophrenia and psychostimulant abuse. 420 Although 5-HT 3 antagonists seem to have no effect in normal animals, they do have actions in animals with abnormal behavior, particularly where dopamine function has been increased.…”

“…The receptor is expressed in both enterochromaffin cells and enteric neurons. In enteric nerve and muscle, 5-HT 4 stimulation facilitates acetylcholine release and relaxation of the colon. , Accordingly, therapeutics that are agonists of this receptor have been used in the clinic to treat both constipation and constipation-predominant irritable bowel syndrome (IBS). , Recently, however, the most widely prescribed therapeutic for these conditions, Tegaserod (Zelnorm), was withdrawn from the market in a number of countries due to increases in potentially fatal cardiovascular events, in particular heart attacks and strokes, observed in clinical trials. Although the molecular basis of these adverse events is currently unknown, they could result from activation of 5-HT 4 receptors expressed in the heart, which may modulate calcium currents. , Conversely, development of 5-HT 4 antagonists may have potential for treating cardiac arrhythmias …”

Effectiveness of Probiotics in the Treatment of Irritable Bowel Syndrome

“…As a gastrointestinal disorder, IBS is chronically relapsing and remitting, and it is associated with a high placebo response rate ranging from 23-43%. 11 This finding may lead to the conclusion that a treatment group may benefit in an uncontrolled setting. To account for this bias, we included only blinded, placebo-controlled trials.…”

Mosapride in the Treatment of Gastrointestinal Disorders

“…Additionally, global relief in gastrointestinal symptoms was higher in the tegaserod group as compared to placebo. Tegaserod also improved abdominal pain in women with IBS-C. 5 Although tegaserod appeared to be a promising medication in the treatment of IBS-C and chronic idiopathic constipation, problems with tegaserod also became apparent. In March 2007, Novartis Pharmaceuticals offered the FDA results of 29 clinical studies of 11,614 patients with Zelnorm ® for the treatment of a variety of gastrointestinal tract conditions.…”