Background: Tegaserod (Zelnorm®) is a 5-hydroxytryptamine (serotonin) type
4 receptor agonist for the treatment of hypomotility disorders of the lower gastrointestinal
tract associated with the irritable bowel syndrome with constipation (IBS-C).
Objective: The authors provide the reader with a better understanding on tegaserod mechanism
of action, on its pharmacodynamics and pharmacokinetic properties, on safety and
tolerability, with a summary of the key published clinical trials conducted in patients with
irritable bowel syndrome (IBS). Its effects on colon inflammation have also been described.
Results: Tegaserod was withdrawn in 2007 due to increased risks of cardiovascular adverse
effects. The manufacturer denied this, because pre-existing cardiovascular disease or
risk factors were attributed to all affected patients. Thus, no causal relationship between
tegaserod use and cardiovascular events was clearly shown. A matched case-control study
of tegaserod-treated with untreated patients found no association between tegaserod and
adverse cardiovascular outcomes. Despite its adverse effects, tegaserod resulted to be effective
in treating chronic constipation in adult women aged < 65 years with IBS-C, while
the safety and effectiveness of tegaserod in men with IBS-C have not been established.
Conclusion: Tegaserod was resubmitted to the Food and Drug Administration in 2018 for
use in a low-risk population. Moreover, tegaserod has also been shown to improve symptoms,
enhance gastric accommodation and significantly attenuate visceral pain arising from
the colon in functional dyspepsia patients. Treatment with tegaserod seems also to exert a
protective effect in inflamed colons, reducing the severity of colitis in animal models.