Importance of the field: The main therapeutic area of 5-HT(3) receptor antagonists is the treatment of chemotherapy-induced nausea and vomiting (CINV), which is the most common and distressing side effects of anticancer treatment. The second major clinical application of 5-HT(3) receptor antagonists is in the treatment of irritable bowel syndrome (IBS). 5-HT(3) antagonists have been widely used and found to decrease gut transit, increase fluid absorption and reduce pain. The uses of 5-HT(3) antagonists are expending to treatment of CNS diseases such as anxiety and sleep disorders as antipsychotics and so on.
Areas covered in this review: The structures, in vitro activities, in vivo effects and some clinical data on 5-HT(3) receptor antagonists under development.
What the reader will gain: Future research directions in 5-HT(3) antagonists based on the clinical trial data of the pipeline molecules.
Take home message: Most drug candidates in clinical trials were discovered in the early 1990s and their patent expiry is imminent. Acquiring intellectual properties of novel 5-HT(3) receptor antagonists with improved efficacies would provide a bright future. Particularly, as the current 5-HT(3) receptor antagonists are classified into only three representative structural families (one third are zacopride-like benzamides and the others are ondansteron-like tricyclic compounds and dolansetron-like bicyclic compounds), structurally diverse compound libraries need to be extensively investigated for identification of novel 5-HT(3) receptor antagonists.