Neuropharmacology of emesis in relation to clinical response.
5-HT3 receptor antagonists such as ondansetron, granisetron, ICS205-930 and zacopride are highly effective in the ferret, cat or dog to prevent emesis caused by cisplatin and other chemotherapeutic agents, and radiation treatment. The anti-emetic effects may be mediated centrally in the area postrema and associated structures of the emetic reflex such as the nucleus tractus solitarius, which have a very high density of 5-HT3 receptors. Additional sites of action may be found on the 5-HT3 receptors located on the vagus nerve or enteric neuronal elements in the gastro-intestinal tract. The precise site(s) and mechanism(s) of action of different cytotoxic treatments to induce emesis remains to be determined, but appears to involve a common action on a 5-HT3 system. The 5-HT3 receptor antagonists do not impair normal behaviour and, in particular, fail to affect the extrapyramidal motor system and do not cause sedation. Of potential benefit, the 5-HT3 receptor antagonists have an anxiolytic profile of action in rodent and primate models. The 5-HT3 receptor antagonists are revealed as an important group of drugs to prevent emesis induced by a wide range of cytotoxic treatments.
Costall
B
B
Postgraduate Studies in Pharmacology, School of Pharmacy, University of Bradford, West Yorkshire, UK.
Naylor
R J
RJ
D000818:Animals; D000932:Antiemetics / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000633:toxicity*; D002945:Cisplatin / Q000633:toxicity*; D006801:Humans; D009325:Nausea / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D009420:Nervous System / Q000503:physiopathology; D009424:Nervous System Physiological Phenomena; D011878:Radiotherapy / Q000009:adverse effects*; D012702:Serotonin Antagonists; D014839:Vomiting / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*
D000932:Antiemetics; D000970:Antineoplastic Agents; D012702:Serotonin Antagonists; D002945:Cisplatin