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Characteristics of antiemetic drugs

George F Longstreth, MD
Paul J Hesketh, MD
Section Editor
Nicholas J Talley, MD, PhD
Deputy Editor
Shilpa Grover, MD, MPH


Several classes of antiemetic drugs are available that antagonize the neurotransmitter receptors known to be involved in the physiology of nausea and vomiting. The antiemetic drugs are classified according to their primary action; some agents affect multiple receptors.

Five neurotransmitter receptor sites are of primary importance in the vomiting reflex:

M1 – muscarinic

D2 – dopamine

H1 – histamine


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Literature review current through: Sep 2016. | This topic last updated: Oct 8, 2015.
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  1. Miller AD. Central mechanisms of vomiting. Dig Dis Sci 1999; 44:39S.
  2. Hornby PJ. Central neurocircuitry associated with emesis. Am J Med 2001; 111 Suppl 8A:106S.
  3. Clissold SP, Heel RC. Transdermal hyoscine (Scopolamine). A preliminary review of its pharmacodynamic properties and therapeutic efficacy. Drugs 1985; 29:189.
  5. Bardfield PA. A controlled double-blind study of trimethobenzamide, prochlorperazine, and placebo. JAMA 1966; 166:796.
  6. Gralla RJ, Itri LM, Pisko SE, et al. Antiemetic efficacy of high-dose metoclopramide: randomized trials with placebo and prochlorperazine in patients with chemotherapy-induced nausea and vomiting. N Engl J Med 1981; 305:905.
  7. Tramèr MR, Moore RA, Reynolds DJ, McQuay HJ. A quantitative systematic review of ondansetron in treatment of established postoperative nausea and vomiting. BMJ 1997; 314:1088.
  8. Lawrence KR, Nasraway SA. Conduction disturbances associated with administration of butyrophenone antipsychotics in the critically ill: a review of the literature. Pharmacotherapy 1997; 17:531.
  9. Marder SR, Essock SM, Miller AL, et al. Physical health monitoring of patients with schizophrenia. Am J Psychiatry 2004; 161:1334.
  10. Grunberg SM, Gala KV, Lampenfeld M, et al. Comparison of the antiemetic effect of high-dose intravenous metoclopramide and high-dose intravenous haloperidol in a randomized double-blind crossover study. J Clin Oncol 1984; 2:782.
  11. Bateman DN, Rawlins MD, Simpson JM. Extrapyramidal reactions with metoclopramide. Br Med J (Clin Res Ed) 1985; 291:930.
  12. Rao AS, Camilleri M. Review article: metoclopramide and tardive dyskinesia. Aliment Pharmacol Ther 2010; 31:11.
  13. Gralla RJ. Metoclopramide. A review of antiemetic trials. Drugs 1983; 25 Suppl 1:63.
  14. Kris MG, Gralla RJ, Tyson LB, et al. Improved control of cisplatin-induced emesis with high-dose metoclopramide and with combinations of metoclopramide, dexamethasone, and diphenhydramine. Results of consecutive trials in 255 patients. Cancer 1985; 55:527.
  15. Roila F, Tonato M, Basurto C, et al. Antiemetic activity of high doses of metoclopramide combined with methylprednisolone versus metoclopramide alone in cisplatin-treated cancer patients: a randomized double-blind trial of the Italian Oncology Group for Clinical Research. J Clin Oncol 1987; 5:141.
  16. Ganzini L, Casey DE, Hoffman WF, McCall AL. The prevalence of metoclopramide-induced tardive dyskinesia and acute extrapyramidal movement disorders. Arch Intern Med 1993; 153:1469.
  17. Hurley JD, Eshelman FN. Trimethobenzamide HCl in the treatment of nausea and vomiting associated with antineoplastic chemotherapy. J Clin Pharmacol 1980; 20:352.
  18. McNulty R. Are all 5-HT3 receptor antagonists the same? J Natl Compr Canc Netw 2007; 5:35.
  19. Tavorath R, Hesketh PJ. Drug treatment of chemotherapy-induced delayed emesis. Drugs 1996; 52:639.
  20. Kaizer L, Warr D, Hoskins P, et al. Effect of schedule and maintenance on the antiemetic efficacy of ondansetron combined with dexamethasone in acute and delayed nausea and emesis in patients receiving moderately emetogenic chemotherapy: a phase III trial by the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 1994; 12:1050.
  21. Hesketh P, Navari R, Grote T, et al. Double-blind, randomized comparison of the antiemetic efficacy of intravenous dolasetron mesylate and intravenous ondansetron in the prevention of acute cisplatin-induced emesis in patients with cancer. Dolasetron Comparative Chemotherapy-induced Emesis Prevention Group. J Clin Oncol 1996; 14:2242.
  22. Navari R, Gandara D, Hesketh P, et al. Comparative clinical trial of granisetron and ondansetron in the prophylaxis of cisplatin-induced emesis. The Granisetron Study Group. J Clin Oncol 1995; 13:1242.
  23. Marty M, Kleisbauer JP, Fournel P, et al. Is Navoban (tropisetron) as effective as Zofran (ondansetron) in cisplatin-induced emesis? The French Navoban Study Group. Anticancer Drugs 1995; 6 Suppl 1:15.
  24. Eisenberg P, Figueroa-Vadillo J, Zamora R, et al. Improved prevention of moderately emetogenic chemotherapy-induced nausea and vomiting with palonosetron, a pharmacologically novel 5-HT3 receptor antagonist: results of a phase III, single-dose trial versus dolasetron. Cancer 2003; 98:2473.
  25. Gralla R, Lichinitser M, Van Der Vegt S, et al. Palonosetron improves prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy: results of a double-blind randomized phase III trial comparing single doses of palonosetron with ondansetron. Ann Oncol 2003; 14:1570.
  26. Saito M, Aogi K, Sekine I, et al. Palonosetron plus dexamethasone versus granisetron plus dexamethasone for prevention of nausea and vomiting during chemotherapy: a double-blind, double-dummy, randomised, comparative phase III trial. Lancet Oncol 2009; 10:115.
  27. Gralla RJ, Navari RM, Hesketh PJ, et al. Single-dose oral granisetron has equivalent antiemetic efficacy to intravenous ondansetron for highly emetogenic cisplatin-based chemotherapy. J Clin Oncol 1998; 16:1568.
  28. Perez EA, Hesketh P, Sandbach J, et al. Comparison of single-dose oral granisetron versus intravenous ondansetron in the prevention of nausea and vomiting induced by moderately emetogenic chemotherapy: a multicenter, double-blind, randomized parallel study. J Clin Oncol 1998; 16:754.
  29. Ettinger DS, Eisenberg PD, Fitts D, et al. A double-blind comparison of the efficacy of two dose regimens of oral granisetron in preventing acute emesis in patients receiving moderately emetogenic chemotherapy. Cancer 1996; 78:144.
  30. Harman GS, Omura GA, Ryan K, et al. A randomized, double-blind comparison of single-dose and divided multiple-dose dolasetron for cisplatin-induced emesis. Cancer Chemother Pharmacol 1996; 38:323.
  31. Navari RM, Koeller JM. Electrocardiographic and cardiovascular effects of the 5-hydroxytryptamine3 receptor antagonists. Ann Pharmacother 2003; 37:1276.
  32. Pinarli FG, Elli M, Dagdemir A, et al. Electrocardiographic findings after 5-HT3 receptor antagonists and chemotherapy in children with cancer. Pediatr Blood Cancer 2006; 47:567.
  33. Keller GA, Ponte ML, Di Girolamo G. Other drugs acting on nervous system associated with QT-interval prolongation. Curr Drug Saf 2010; 5:105.
  34. Turner S, Mathews L, Pandharipande P, Thompson R. Dolasetron-induced torsades de pointes. J Clin Anesth 2007; 19:622.
  35. US Food and Drug Administration. Zofran (ondansetron): Drug Safety Communication - Risk of Abnormal Heart Rhythms. www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm272041.htm (Accessed on September 20, 2011).
  36. Benline TA, French J. Anti-emetic drug effects on cognitive and psychomotor performance: granisetron vs. ondansetron. Aviat Space Environ Med 1997; 68:504.
  37. Saito R, Takano Y, Kamiya HO. Roles of substance P and NK(1) receptor in the brainstem in the development of emesis. J Pharmacol Sci 2003; 91:87.
  38. Tattersall FD, Rycroft W, Francis B, et al. Tachykinin NK1 receptor antagonists act centrally to inhibit emesis induced by the chemotherapeutic agent cisplatin in ferrets. Neuropharmacology 1996; 35:1121.
  39. Gralla RJ, Bosnjak SM, Hontsa A, et al. A phase III study evaluating the safety and efficacy of NEPA, a fixed-dose combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting over repeated cycles of chemotherapy. Ann Oncol 2014; 25:1333.
  40. dos Santos LV, Souza FH, Brunetto AT, et al. Neurokinin-1 receptor antagonists for chemotherapy-induced nausea and vomiting: a systematic review. J Natl Cancer Inst 2012; 104:1280.
  41. Rapoport BL, Chasen MR, Gridelli C, et al. Safety and efficacy of rolapitant for prevention of chemotherapy-induced nausea and vomiting after administration of cisplatin-based highly emetogenic chemotherapy in patients with cancer: two randomised, active-controlled, double-blind, phase 3 trials. Lancet Oncol 2015; 16:1079.
  42. Campos D, Pereira JR, Reinhardt RR, et al. Prevention of cisplatin-induced emesis by the oral neurokinin-1 antagonist, MK-869, in combination with granisetron and dexamethasone or with dexamethasone alone. J Clin Oncol 2001; 19:1759.
  43. Basch E, Prestrud AA, Hesketh PJ, et al. Antiemetics: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 2011; 29:4189.
  44. Roila F, Herrstedt J, Aapro M, et al. Guideline update for MASCC and ESMO in the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting: results of the Perugia consensus conference. Ann Oncol 2010; 21 Suppl 5:v232.
  45. de Jong FA, Engels FK, Mathijssen RH, et al. Medicinal cannabis in oncology practice: still a bridge too far? J Clin Oncol 2005; 23:2886.
  46. Sallan SE, Zinberg NE, Frei E 3rd. Antiemetic effect of delta-9-tetrahydrocannabinol in patients receiving cancer chemotherapy. N Engl J Med 1975; 293:795.
  47. Sallan SE, Cronin C, Zelen M, Zinberg NE. Antiemetics in patients receiving chemotherapy for cancer: a randomized comparison of delta-9-tetrahydrocannabinol and prochlorperazine. N Engl J Med 1980; 302:135.
  48. Gralla RJ, Tyson LB, Bordin LA, et al. Antiemetic therapy: a review of recent studies and a report of a random assignment trial comparing metoclopramide with delta-9-tetrahydrocannabinol. Cancer Treat Rep 1984; 68:163.
  49. Jordan K, Schmoll HJ, Aapro MS. Comparative activity of antiemetic drugs. Crit Rev Oncol Hematol 2007; 61:162.
  50. Bowcock SJ, Stockdale AD, Bolton JA, et al. Antiemetic prophylaxis with high dose metoclopramide or lorazepam in vomiting induced by chemotherapy. Br Med J (Clin Res Ed) 1984; 288:1879.
  51. Kris MG, Gralla RJ, Clark RA, et al. Antiemetic control and prevention of side effects of anti-cancer therapy with lorazepam or diphenhydramine when used in combination with metoclopramide plus dexamethasone. A double-blind, randomized trial. Cancer 1987; 60:2816.