title: Therapeutic potential of drugs with mixed 5-HT4 agonist/5-HT3 antagonist action in the control of emesis.
abstract: Drugs interacting with serotonin (5-hydroxytryptamine, 5-HT) receptors are of value in the treatment of several gastrointestinal disturbances. Selective 5-HT3 receptor antagonists (ondansetron, granisetron, tropisetron) are widely utilized to control emesis induced by chemotherapy and radiation, while agonists at 5-HT4 receptors (cisapride, renzapride, BIMU compounds) are endowed with gastrointestinal prokinetic action. Here we overview the therapeutic potential of drugs with potent mixed 5-HT4 agonist/5-HT3 antagonist properties (i.e. BIMU 1) in the management of anticancer therapy-induced emesis and of intestinal adynamic post-operative conditions associated with vomiting. In the former situation, the agonism at 5-HT4 receptors is expected to be of benefit via two possible mechanism: (i) inhibition of 5-HT release from enterochromaffin cells; (ii) restoration of anally driven peristaltic waves in the upper gastrointestinal tract. Moreover, 5-HT4 receptor-induced prokinetic activity may counteract colonic constipation, an unwanted effect which occurs in a number of patients treated with pure 5-HT3 receptor antagonists. Additionally, the above mentioned drugs might be of value in post-operative conditions associated with intestinal adynamia and emesis sensitive to 5-HT3 receptor blockade.
mesh_terms: D000818:Animals; D002945:Cisplatin / Q000009:adverse effects; D064420:Drug-Related Side Effects and Adverse Reactions; D011985:Receptors, Serotonin / Q000145:classification / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000627:therapeutic use*; D017366:Serotonin Receptor Agonists / Q000627:therapeutic use*; D014839:Vomiting / Q000188:drug therapy*
chemical_list: D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D002945:Cisplatin