<unk> s are most effective in the prevention and treatment of chemotherapy-induced nausea and vomiting (CINV), especially that caused by highly emetogenic drugs such as cisplatin; when used for this purpose, they may be given alone or, more frequently, with a glucocorticoid, usually dexamethasone. They are usually given intravenously, shortly before administration of the chemotherapeutic agent, although some authors have argued that oral administration may be preferred. The concomitant administration of a NK1 receptor antagonist, such as aprepitant, significantly increases the efficacy of<unk> s in preventing both acute and delayed CINV. The<unk> s are also indicated in the prevention and treatment of radiation-induced nausea and vomiting (RINV), when needed, and postoperative nausea and vomiting (PONV). Although they are more effective at controlling CINV—where they stop symptoms altogether in up to 70% of people, and reduce them in the remaining 30%—, they are just as effective as other agents for PONV. Current evidence suggests that<unk> s are ineffective in controlling motion sickness. A randomized, placebo-controlled trial of ondansetron to treat motion sickness in air ambulance personnel showed subjective improvement, but it was not statistically significant. Available agents *Ondansetron was the first<unk> , developed by Glaxo around 1984. Its efficacy was first established in 1987, in animal models, and it was extensively studied over the following years. Ondansetron was approved by the U.S. Food and Drug Administration in 1991, and has since become available in several other countries, including the UK, Ireland, Australia, Canada, France and Brazil. As of 2008, ondansetron and granisetron are the only<unk> s available as a generic drug in the United States. Ondansetron may be given several times daily, depending on the severity of symptoms. *Tropisetron was also first described in 1984. It is available in several countries, such as the UK, Australia and France, but not in the United States. The effects of tropisetron last up to 24 hours, so it only requires once-daily administration. *Granisetron was developed around 1988. It is available in the U.S., UK, Australia and other countries. Clinical trials suggest that it is more effective than other<unk> s in preventing delayed CINV (nausea and vomiting that occur more than 24 hours after the first dose of chemotherapy). It is taken once daily. *Dolasetron was first mentioned in the literature in 1989. It is a prodrug, and most of its effects are due to its active metabolite, hydrodolasetron, which is formed in the liver by the enzyme carbonyl reductase. Dolasetron was approved by the FDA in 1997, and is also administered once daily. *Palonosetron is the newest<unk>  to become available in the U.S. market. It is an isoquinoline derivative, and is effective in preventing delayed CINV. Palonosetron was approved by the FDA in 2003, initially for intravenous use. An oral formulation was approved on August 22, 2008 for prevention of acute CINV alone, as a large clinical trial did not show oral administration to be as effective as IV use against delayed CINV. *Ramosetron is only available in Japan and certain Southeast Asian countries as of 2008. It has higher affinity for the 5-HT3 receptor than the older<unk> s, and maintains its effects over two days; it is therefore significantly more effective for delayed CINV. In animal studies, ramosetron was also effective against irritable bowel syndrome-like symptoms. Alosetron and cilansetron—the latter was developed by Solvay but never approved by the FDA —are not antiemetics; instead, they are indicated in the treatment of a subset of irritable bowel syndrome where diarrhea is the dominant symptom. Alosetron was withdrawn from the U.S. market in 2000 due to unacceptably frequent severe side effects, including ischemic colitis, and is only available through a restrictive program to patients who meet certain requirements. Certain prokinetic drugs such as cisapride, renzapride and metoclopramide, although not<unk> s proper, possess some weak antagonist effect at the 5-HT3 receptor. Galanolactone, a diterpenoid found in ginger, is a<unk>  and is believed to at least partially mediate the anti-emetic activity of this plant. Mirtazapine is a tetracyclic antidepressant with 5-HT2 and<unk>  effects that also possesses strong anti-emetic properties, however it is also very sedating. Studies show that Mirtazapine is as equally effective in treating chemotherapy-related nausea and vomiting as standard treatments; it is also cheaper and has fewer side effects than typical anti-emetics, and its antidepressant qualities may be an added benefit for cancer populations. Mirtazapine has also been used in the treatment of the motility disorder gastroparesis due to its anti-emetic effects. Olanzapine, an atypical antipsychotic with anti-emetic properties similar to those of Mirtazapine, also shows promise in treating chemotherapy-induced nausea and vomiting.
5-HT3 antagonist
Opioid antagonist
Dopamine antagonist
Dopamine agonist
GABA reuptake inhibitor
Adenosine reuptake inhibitor
5-HT2C receptor agonist
NMDA receptor antagonist