Nausea and Vomiting

  • Pernille H. Hansen
  • Jesper Palshof
  • Jørn Herrstedt


Despite the fact that research in the mechanism of vomiting goes back more than 300 years, there are still major gaps in our knowledge. The first report of the clinical use of an antineoplastic drug was published in 1942, but it was not until cisplatin, the most emetogenic of all drugs, was approved in 1978, the necessity of focusing on antiemetic research became evident.

This chapter will focus on the biological basis of nausea and vomiting from the time of the very simple animal experiments, suggesting the existence of a vomiting center, to current research methodology enabling precise subdivision of receptors involved in the emetic reflex arch.


Antineoplastic Agent Area Postrema Antiemetic Effect Dopamine Receptor Antagonist Serotonin Receptor Antagonist 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Wepfer JJ. Historia cicutae aquaticae. Basel. 1679;152.Google Scholar
  2. 2.
    Mellinger C. Beitrage zur Kenntniff des Erbrechens. Pfluegers Arch. 1881;24:232–40.Google Scholar
  3. 3.
    Cannon WB. The movement of the stomach studied by means of the röntgen rays. Am J Physiol. 1898;1:359–82.Google Scholar
  4. 4.
    Giannuzzi G. Untersuchungen über die Organe, welche an dem Brechaet theilnehmen, und über die Physiologische Wirkung de Tartarus stibiatic. Zent Med Wizz. 1865;3:129–31.Google Scholar
  5. 5.
    Thumas LJ. Über das Brechcentrum und über die Wirkung einiger pharmakologischer Mittel auf dasselbe. Arch für Patol Anat. 1891;123:44–69.Google Scholar
  6. 6.
    Hatcher RA, Weiss S. Studies on vomiting. J Pharmacol Exp Ther. 1923;22:139–93.Google Scholar
  7. 7.
    Borison HL, Wang SC. Functional location of central coordinating mechanism for emesis in cat. J Physiol. 1949;12:305–13.Google Scholar
  8. 8.
    Wang SC, Borison HL. Copper sulphate emesis: a study of afferent pathways from the gastrointestinal tract. J Physiol. 1951;14:520–6.Google Scholar
  9. 9.
    Borison HL, Wang SC. Locus of the central emetic action of cardiac glycosides. J Physiol. 1951;76:335–8.Google Scholar
  10. 10.
    Wang SC, Borison HL. A new concept of organization of the central emetic mechanism: recent studies on sites of action of apomorphine, copper sulphate and cardiac glycosides. Gastroenterology. 1952;22:1–12.PubMedGoogle Scholar
  11. 11.
    Borison HL, Wang SC. Physiology and pharmacology of vomiting. Pharmacol Rev. 1953;5:193–230.PubMedGoogle Scholar
  12. 12.
    Lindstrom PA, Brizze KR. Relief of intractable vomiting from surgical lesions in the area postrema. J Neurosurg. 1962;19:228–36.PubMedGoogle Scholar
  13. 13.
    Miller AD, Wilson VJ. “Vomiting center” reanalyzed: an electrical stimulation study. Brain Res. 1983;270:154–8.PubMedGoogle Scholar
  14. 14.
    Miller AD, Nonaka S, Jakûs J. Brain areas essential or non-essential for emesis. Brain Res. 1994;647:255–64.PubMedGoogle Scholar
  15. 15.
    Carpenter DO. Neural mechanisms of emesis. Can J Physiol Pharmacol. 1990;68:230–6.PubMedGoogle Scholar
  16. 16.
    Carl PL, Cubeddu LX, Lindley C, Myers RD, Rezvani AH. Do humoral factors mediate cancer chemotherapy-induced emesis? Drug Metab Rev. 1989;21:319–33.PubMedGoogle Scholar
  17. 17.
    Peroutka SJ. Chemotherapeutic agents do not interact with neurotransmitter receptors. Cancer Chemother Pharmacol. 1987;19:131–2.PubMedGoogle Scholar
  18. 18.
    Herrstedt J, Hyttel J, Pedersen J. Interaction of the antiemetic metopimazine and anticancer agents with brain dopamine D2, 5-hydroxytryptamine3, histamine H1, muscarine cholinergic and α1-adrenergic receptors. Cancer Chemother Pharmacol. 1993;33:53–6.PubMedGoogle Scholar
  19. 19.
    Herrstedt J. Antiemetics: an update and the MASCC guidelines applied in clinical practice. Nat Clin Pract Oncol. 2008;5:32–43.PubMedGoogle Scholar
  20. 20.
    Carlsson A, Lindqvist M, Magnusson T. 3,4-Dihydroxyphenylalanine and 5-hydroxytryptophan as reserpine antagonists. Nature. 1957;180:1200.PubMedGoogle Scholar
  21. 21.
    Iversen SD, Iversen LL. Dopamine: 50 years in perspective. Trends Neurosci. 2007;30:188–93.PubMedGoogle Scholar
  22. 22.
    Anden NE, Carlsson A, Dahlstroem A, Fuxe K, Hillarp NA, Larsson K. Demonstration and mapping out of nigro-neostriatal dopamine neurons. Life Sci. 1964;3:523–30.PubMedGoogle Scholar
  23. 23.
    Dahlstroem A, Fuxe K. Evidence for the existence of monoamine- containing neurons in the central nervous system. I. Demonstration of mono- amines in the cell bodies of brain stem neurons. Acta Physiol Scand. 1964;232(Suppl):231–55.Google Scholar
  24. 24.
    Bunney B. Antipsychotic drug effects on the electrical activity of dopaminergic neurons. Trends Neurosci. 1984;7:212–5.Google Scholar
  25. 25.
    Kebabian JW, Petzold GL, Greengard P. Dopamine-sensitive adenylate cyclase in caudate nucleus of rat brain, and its similarity to the “dopamine receptor”. Proc Natl Acad Sci. 1972;69:2145–9.PubMedGoogle Scholar
  26. 26.
    Kebabian JW, Calne DB. Multiple receptors for dopamine. Nature. 1979;277:93–6.PubMedGoogle Scholar
  27. 27.
    Katzman R, Markman MH, Ahn HS, Mishra RK, Gardner E. Effects of drugs and lesions on dopamine-stimulated adenylate cyclase: evidence for different classes of dopamine receptors. Trans Am Neurol Assoc. 1977;102:76–9.PubMedGoogle Scholar
  28. 28.
    Beaulieu JM, Gainetdinov RR. The physiology, signaling and pharmacology of dopamine receptors. Pharmacol Rev. 2011;63:182–217.PubMedGoogle Scholar
  29. 29.
    Missale C, Nash SR, Robinson SW, Jaber M, Caron MG. Dopamine receptors: from structure to function. Physiol Rev. 1998;78:189–225.PubMedGoogle Scholar
  30. 30.
    Carlsson A. A paradigm shift in brain research. Science. 2001;294:1021–4.PubMedGoogle Scholar
  31. 31.
    Bunzow JR, Van Tol HH, Grandy DK, et al. Cloning and expression of a rat D2 dopamine receptor cDNA. Nature. 1988;336:783–7.PubMedGoogle Scholar
  32. 32.
    Giros B, Sokoloff P, Martres MP, Riou JF, Emorine LJ, Schwartz JC. Alternative splicing directs the expression of two D2 dopamine receptor isoforms. Nature. 1989;342:923–6.PubMedGoogle Scholar
  33. 33.
    Moertel CG, Reitemeier RJ, Gage RP. A controlled clinical evaluation of antiemetic drugs. JAMA. 1963;186:116–8.PubMedGoogle Scholar
  34. 34.
    Shen WW, Baig MS, Sata LS, Hofstatter L. Dopamine receptor supersensitivity and the chemoreceptor trigger zone. Biol Psychiatry. 1983;18:917–21.PubMedGoogle Scholar
  35. 35.
    Jolliet P, Nion S, Allain-Veyrac G, et al. Evidence of the lowest brain penetration of an antiemetic drug, metopimazine, compared to domperidone, metoclopramide and chlorpromazine, using an in vitro model of the blood–brain barrier. Pharmacol Res. 2007;56:11–7.PubMedGoogle Scholar
  36. 36.
    Sokoloff P, Giros B, Martres M-P, Bouthenet M-L, Schwartz J-C. Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics. Nature. 1990;347(6289):146–51.PubMedGoogle Scholar
  37. 37.
    Yoshida N, Yoshikawa T, Hosoki K. A dopamine D3 receptor agonist, 7-OH-DPAT, causes vomiting in the dog. Life Sci. 1995;57:PL347–50.PubMedGoogle Scholar
  38. 38.
    Yoshikawa T, Yoshida N, Hosoki K. Involvement of dopamine D3 receptors in the area postrema in R(+)-7-OH-DPAT induced emesis in the ferret. Eur J Pharmacol. 1996;301:143–9.PubMedGoogle Scholar
  39. 39.
    Stemp G, Ashmeade T, Branch CL, et al. Design and synthesis of trans-N-[4-[2-(6-cyano-1,2,3, 4-tetrahydroisoquinolin-2-yl)ethyl]cyclohexyl]-4-quinolinecarboxamide (SB-277011): a potent and selective dopamine D3 receptor antagonist with high oral bioavailability and CNS penetration in the rat. J Med Chem. 2000;43:1878–85.PubMedGoogle Scholar
  40. 40.
    Rapport MM, Green AA, Page IH. Partial purification of the vasoconstrictor in beef serum. J Biol Chem. 1948;176:735–41.Google Scholar
  41. 41.
    Rapport MM. Crystalline Serotonin. Science. 1948;108:329–30.Google Scholar
  42. 42.
    Freyburger WA, Graham BE, Rapport MM, et al. The pharmacology of 5-hydroxytryptamine (serotonin). J Pharmacol Exp Ther. 1952;105:80–6.PubMedGoogle Scholar
  43. 43.
    Gaddum JH, Hameed KA. Drugs which antagonize 5-hydroxytryptamine. Br J Pharmacol. 1954;9:240–8.Google Scholar
  44. 44.
    Gaddum JH, Picarelli ZP. Two kinds of tryptamine receptors. Br J Pharmacol. 1957;12:323–8.Google Scholar
  45. 45.
    Peroutka SJ, Snyder SH. Multiple serotonin receptors: differential binding of 3H-5-hydrxytryptamine, 3H-lysergic acid diethylamide and 3H-spiropidol. Mol Pharmacol. 1979;16:687–9.PubMedGoogle Scholar
  46. 46.
    Bradley PB, Engel G, Feniuk W, et al. Proposals for the classification and nomenclature of functional receptors for 5-hydroxytryptamine. Neuropharmacology. 1986;25:563–76.PubMedGoogle Scholar
  47. 47.
    Hoyer D, Clarke DE, Fozard JR, et al. International union of pharmacology classification of receptors for 5-hydroxytryptamine (serotonin). Pharmacol Rev. 1994;46:157–203.PubMedGoogle Scholar
  48. 48.
    Hoyer D, Hannon JP, Martin GR. Molecular, pharmacological and functional diversity of 5-HT receptors. Pharmacol Biochem Behav. 2002;71:533–54.PubMedGoogle Scholar
  49. 49.
    Kilpatrick GJ, Jones BJ, Tyers MB. Identification and distribution of 5-HT3 receptors in the brain using radioligand binding. Nature. 1987;330:746–8.PubMedGoogle Scholar
  50. 50.
    Pratt GD, Bowery NG, Kilpatrick GJ, et al. Consensus meeting agrees about distribution of 5-HT3 receptors in mammalian hindbrain. TIPS. 1990;11:135–7.PubMedGoogle Scholar
  51. 51.
    Belelli D, Balcarek JM, Hope AG, et al. Cloning and functional expression of a human 5-hydroxytryptamine type 3AS receptor subunit. Mol Pharmacol. 1995;48:1054–62.PubMedGoogle Scholar
  52. 52.
    Miyake A, Mochizuki S, Takemoto Y, Akuzawa S. Molecular cloning of human 5-hydroxytryptamine3 receptor: heterogeneity in distribution and function among species. Mol Pharmacol. 1995;48:407–16.PubMedGoogle Scholar
  53. 53.
    Davies PA, Pistis M, Hanna MC, et al. The 5-HT3B subunit is a major determinant of serotonin-receptor function. Nature. 1999;397:359–63.PubMedGoogle Scholar
  54. 54.
    Niesler B, Frank B, Kapeller J, Rappold GA. Cloning, physical mapping and expression analysis of the human 5-HT3 serotonin receptor-like genes HTR3C, HTR3D and HTR3E. Gene. 2003;310:101–11.PubMedGoogle Scholar
  55. 55.
    Niesler B, Kapeller J, Hammer C, Rappold G. Serotonin type 3 receptor genes: HTR3A, B, C, D, E. Pharmacogenomics. 2008;9:501–4.PubMedGoogle Scholar
  56. 56.
    Jensen AA, Davies PA, Braüner-Osborne H, Krzywkowski K. 3B but which 3B? And that’s just one of the questions: the heterogeneity of human 5-HT3 receptors. TIPS. 2008;29:437–44.PubMedGoogle Scholar
  57. 57.
    Niesler B. 5-HT3 receptors: potential of individual isoforms for personalized therapy. Curr Opin Pharmacol. 2011;11:81–6.PubMedGoogle Scholar
  58. 58.
    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 vomiting. N Engl J Med. 1981;305:905–9.PubMedGoogle Scholar
  59. 59.
    Fozard JR, Mobarok ALIA. Blockade of neuronal tryptamine receptors by metoclopramide. Eur J Pharmacol. 1978;49:109–12.PubMedGoogle Scholar
  60. 60.
    Fozard JR. MDL 72222, a potent and highly selective antagonist at neuronal 5-hydroxytryptamine receptors. Naunyn Schmiedebergs Arch Pharmacol. 1984;326:36–44.PubMedGoogle Scholar
  61. 61.
    Costall B, Domeney AM, Naylor RJ, Tattersall FD. 5-hydroxytryptamine M-receptor antagonism to prevent cisplatin-induced emesis. Neuropharmacology. 1986;25:959–61.PubMedGoogle Scholar
  62. 62.
    Miner WD, Sanger GJ. Inhibition of cisplatin-induced vomiting by selective 5-hydroxytryptamine M-receptor antagonism. Br J Pharmacol. 1986;88:497–9.PubMedGoogle Scholar
  63. 63.
    Leibundgut U, Lancranjan I. First results with ICS 205–930 (5-HT3 receptor antagonist) in prevention of chemotherapy-induced emesis. Lancet. 1987;329:1198.Google Scholar
  64. 64.
    Cunningham D, Hawthorne J, Pople A, et al. Prevention of emesis in patients receiving cytotoxic drugs by GR38032F, a selective 5HT 3 receptor antagonist. Lancet. 1987;329:1461–3.Google Scholar
  65. 65.
    Dale HH, Dudley HW. The presence of histamine and acethylcholine in the spleen of the ox and the horse. Physiology. 1929;68:97–123.Google Scholar
  66. 66.
    Von Euler VS, Gaddum JH. An unidentified depressor substance in certain tissue extracts. J Physiol (Lond). 1931;1931:577–83.Google Scholar
  67. 67.
    Lembeck F. Zur Frage der zentralen Ubertragung afferenter Impulse III. Mitteilung. Das Vorkommen und die Bedeutung der Substanz P in den dorsalen Wurzeln des Ruckenmarks. Arch Exp Pathol Pharmakol. 1953;219:197–213.Google Scholar
  68. 68.
    Chang M, Leeman SE. Isolation of sialogogic peptide from bovine hypothalamic tissue and its characteristic as substance P. J Biol Chem. 1970;245:4784–90.PubMedGoogle Scholar
  69. 69.
    Kangawa H, Minamino N, Fukuda A, Matsuo H. Neuromedin K: a novel mammalian tachykinin identified in porcine spinal cord. Biochem Biophys Res Commun. 1983;114:533–40.PubMedGoogle Scholar
  70. 70.
    Kimura S, Okada M, Sugita Y, Kanzawa I, Munekata E. Novel neuropeptides, neurokinin A and B isolated from porcine spinal cord. Proc Jpn Acad. 1983;59B:101–4.Google Scholar
  71. 71.
    Erspamer V. The tachykinin peptides family. Trends Neurosci. 1981;4:267–9.Google Scholar
  72. 72.
    Buck SH, Burcher E, Shults CW, Lovenberg W, O’Donohue TL. Novel pharmacology of substance K–binding sites: a third type of tachykinin receptor. Science. 1984;226:987–9.PubMedGoogle Scholar
  73. 73.
    Laufer R, Gilon C, Chorev M, Selinger Z. Characterization of a neurokinin B receptor site in rat brain using a highly selective radioligand. J Biol Chem. 1986;261:10257–63.PubMedGoogle Scholar
  74. 74.
    Lee C-M, Campbell NJ, Williams BJ, Iversen LL. Multiple tachykinin binding sites in peripheral tissues and in the brain. Eur J Pharmacol. 1986;130:209–17.PubMedGoogle Scholar
  75. 75.
    Masu Y, Nakayama K, Tamaki H, Harada Y, Kuno M, Nakanishi S. cDNA cloning of bovine substance-K receptor through oocyte expression system. Nature. 1987;329:836–8.PubMedGoogle Scholar
  76. 76.
    Yokota Y, Sasai Y, Tanaka K, et al. Molecular characterization of a functional cDNA for rat substance P receptor. J Biol Chem. 1989;264:17649–52.PubMedGoogle Scholar
  77. 77.
    Shigemoto R, Yokota Y, Tsuschida K, Nakanishi S. Cloning and expression of a rat neuromedin K receptor cDNA. J Biol Chem. 1990;265:623–8.PubMedGoogle Scholar
  78. 78.
    Maggi CA, Patacchini R, Roveto P, Giachetti A. Tachykinin receptors and receptor antagonists. J Auton Pharmac. 1993;13:23–93.Google Scholar
  79. 79.
    Leander S, Håkanson R, Rosell S, Folkers K, Sundler F, Tornquist K. A specific substance P antagonist blocks smooth muscle contractions induced by non-cholinergic, non-adrenergic nerve stimulation. Nature. 1981;294:467–9.PubMedGoogle Scholar
  80. 80.
    Snider RM, et al. A potent nonpeptide antagonist of the substance P (NK1) receptor. Science. 1991;251:435–7.PubMedGoogle Scholar
  81. 81.
    Tattersall FD, et al. The tachykinin NK1 receptor antagonist CP-99,994 attenuates cisplatin induced emesis in the ferret. Eur J Pharmacol. 1993;250:R5–6.PubMedGoogle Scholar
  82. 82.
    Kris MG, et al. Use of a NK1 receptor antagonist to prevent delayed emesis after cisplatin. J Natl Cancer Inst. 1997;89:817–8.PubMedGoogle Scholar
  83. 83.
    Harris HL. Cytotoxic therapy-induced vomiting is mediated via enkephalin pathways. Lancet. 1982;1:714–6.PubMedGoogle Scholar
  84. 84.
    Fisher RD, Rentschler RE, Nelson JC, Godfrey TE, Wilbur DW. Elevation of plasma ­antidiuretic hormone (ADH) associated with chemotherapy-induced emesis in man. Cancer Treat Rep. 1982;66:25–9.PubMedGoogle Scholar
  85. 85.
    Perry MR, Rhee J, Smith WL. Plasma levels of peptide YY correlate with cisplatin-induced emesis in dogs. J Pharm Pharmacol. 1994;46:553–7.PubMedGoogle Scholar
  86. 86.
    Rudd JA, Ngan MP, Wai MK, et al. Anti-emetic activity of ghrelin in ferrets exposed to the cytotoxic anticancer agent cisplatin. Neurosci Lett. 2006;392:79–83.PubMedGoogle Scholar
  87. 87.
    Walsh D, Nelson KA, Mahmoud FA. Established and potential therapeutic applications of cannabinoids in oncology. Support Care Cancer. 2003;11:137–43.PubMedGoogle Scholar
  88. 88.
    Rocha M, Stéfano SC, De Cássia HR, Oliveira R, Da Silveira DX. Therapeutic use of cannabis sativa on chemotherapy-induced nausea and vomiting among cancer patients: systematic review and meta-analysis. Eur J Cancer Care. 2008;17:431–43.Google Scholar
  89. 89.
    Ahlquist RP. A study of adrenotropic receptors. Am J Physiol. 1948;153:586.PubMedGoogle Scholar
  90. 90.
    Jenkins LC, Lahay D. Central mechanisms of vomiting related to catecholamines response: anaesthetic implication. Can Anaesth Soc J. 1971;18:434–41.PubMedGoogle Scholar
  91. 91.
    Borison HL. Area postrema: chemoreceptor circumventricular organ of the medulla oblongata. Prog Neurobiol. 1989;32:351–90.PubMedGoogle Scholar
  92. 92.
    Lang IM, Sarna SK. The role of adrenergic receptors in the initiation of vomiting and its gastrointestinal motor correlates. J Pharmacol Exp Ther. 1991;263:395–403.Google Scholar
  93. 93.
    Beleslin DB, Strbac M. Noradrenaline-induced emesis: alpha-2 adrenoreceptor mediation in the area postrema. Neuropharmacology. 1987;26:1157–65.PubMedGoogle Scholar
  94. 94.
    Fredrikson M, Hursi T, Steineck G, Fürst CJ, Börjesson S, Peterson C. Delayed chemotherapy-induced nausea is augmented by high levels of endogenous noradrenaline. Br J Cancer. 1994;70:642–5.PubMedGoogle Scholar
  95. 95.
    Showell GA, Barnes MJ, Daiss JO, et al. (R)-sila-venlafaxine: a selective noradrenaline reuptake inhibitor for the treatment of emesis. Bioorg Med Chem Lett. 2006;16:2555–8.PubMedGoogle Scholar
  96. 96.
    Warneck JB, Cheng FH, Barnes MJ, et al. Action of (R)-sila-venlafaxine and reboxetine to antagonize cisplatin-induced acute and delayed emesis in the ferret. Toxicol Appl Pharmacol. 2008;232:369–75.PubMedGoogle Scholar
  97. 97.
    Du Bois A, Kriesinger-Schroeder H, Meerpohl H-G. The role of serotonin as a mediator of emesis induced by different stimuli. Support Care Cancer. 1995;3:285–90.PubMedGoogle Scholar
  98. 98.
    Cubeddu LX, Hoffmann IS, Fuenmayor NT, Malave JJ. Changes in serotonin metabolism in cancer patients: its relationship to nausea and vomiting induced by chemotherapeutic drugs. Br J Cancer. 1992;66:198–203.PubMedGoogle Scholar
  99. 99.
    Cubeddu LX, Hoffmann IS. Participation of serotonin on early and delayed emesis induced by initial and subsequent cyles of cisplatinum-based chemotherapy: effects of antiemetics. J Clin Pharmacol. 1993;33:691–7.PubMedGoogle Scholar
  100. 100.
    De Wit R, Schmitz PIM, Verweij J, et al. Analysis of cumulative probabilities show, that the efficacy of 5-HT3 antagonist prophylaxis is not maintained. J Clin Oncol. 1996;14:644–51.PubMedGoogle Scholar
  101. 101.
    Csillik-Perczel V, Bakonyi A, Yemane T, et al. GYKI-46903, a non-competitive antagonist for 5-HT3 receptors. Pharmacol Toxicol. 1996;79:32–9.PubMedGoogle Scholar
  102. 102.
    Rojas C, Stathis M, Thomas AG, et al. Palonosetron exhibits unique molecular interactions with the 5-HT3 receptor. Anaesth Analg. 2008;107:469–78.Google Scholar
  103. 103.
    Rojas C, Slusher BS. Pharmacological mechanisms of 5-HT3 and tachykinin NK1 receptor antagonism to prevent chemotherapy-induced nausea and vomiting. Eur J Pharmacol. 2012;684:1–7.PubMedGoogle Scholar
  104. 104.
    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, randomized, comparative Phase III trial. Lancet Oncol. 2009;10:115–24.PubMedGoogle Scholar
  105. 105.
    Borison HL, McCarthy LE. Neuropharmacology of chemotherapy-induced emesis. Drugs. 1983;25 Suppl 1:8–17.PubMedGoogle Scholar
  106. 106.
    Cubeddu LX, Hoffmann IS, Fuenmayor NT, Finn AL. Efficacy of ondansetron (GR 38032) and the role of serotonin in cisplatin-induced nausea and vomiting. N Engl J Med. 1990;322:810–6.PubMedGoogle Scholar
  107. 107.
    Fetting J, Grochow LB, Folstein MF, Ettinger DS, Colvin M. The course of nausea and ­vomiting after high-dose cyclophosphamide. Cancer Treat Rep. 1982;66:1487–93.PubMedGoogle Scholar
  108. 108.
    Beck TM. The pattern of emesis following high-dose cyclophosphamide and the antiemetic efficacy of ondansetron. Anti Cancer Drugs. 1995;6:237–42.PubMedGoogle Scholar
  109. 109.
    Martin M, Diaz-Rubio E, Sánchez A, Almenarez J, López-Vega JM. The natural course of emesis after carboplatin treatment. Acta Oncol. 1990;29:593–5.PubMedGoogle Scholar
  110. 110.
    Herrstedt J, Sigsgaard T, Handberg J, Schousboe BMB, Hansen M, Dombernowsky P. Randomized, double-blind comparison of ondansetron versus ondansetron plus metopimazine as antiemetic prophylaxis during platinum-based chemotherapy in patients with cancer. J Clin Oncol. 1997;15:1690–6.PubMedGoogle Scholar
  111. 111.
    Hesketh PJ, Warr DG, Street JC, Carides AD. Differential time course of action of the 5-HT3 and NK1 receptor antagonists when used with highly and moderately emetogenic chemotherapy (HEC and MEC). Support Care Cancer. 2011;19:1297–302.PubMedGoogle Scholar
  112. 112.
    Blier P. Crosstalk between the norepinephrine and serotonin systems and its role in antidepressant response. J Psychiatry Neurosci. 2001;26(Suppl):S3–10.PubMedGoogle Scholar
  113. 113.
    Di Giovanni G, Esposito E, Di Matteo V. Role of serotonin in central dopamine dysfunction. CNS Neurosci Ther. 2010;16:179–94.PubMedGoogle Scholar
  114. 114.
    Werkman TR, McCreary AC, Kruse CG, Wadman WJ. NK3 receptors mediate an increase in firing rate of midbrain dopamine neurons of the rat and guinea pig. Synapse. 2011;65:814–26.PubMedGoogle Scholar
  115. 115.
    Jovanovic-Micic D, Samardzic R, Beleslin DB. The role of α-adrenergic mechanisms within the area postrema in dopamine-induced emesis. Eur J Pharmacol. 1995;272:21–30.PubMedGoogle Scholar
  116. 116.
    Rojas C, Li Y, Zhang J, et al. The antiemetic 5-HT3 receptor antagonist palonosetron inhibits substance P-mediated responses in vitro and in vivo. J Pharmacol Exp Ther. 2010;335:362–8.PubMedGoogle Scholar
  117. 117.
    Darmani NA, Chebolu S, Amos B, Alkam T. Synergistic antiemetic interactions between serotonergic 5-HT3 and tachykininergic NK1-receptor antagonists in the last shrew (Cryptotis parva). Pharmacol Biochem Behav. 2011;99:573–9.PubMedGoogle Scholar
  118. 118.
    Goodman LS, Wintrobe MM, Dameshek W, et al. Nitrogen mustard therapy; use of methyl-bis (beta-chloroethyl) amine hydrochloride and tris (beta-chloroethyl) amine hydrochloride for Hodgkin’s disease, lymphosarcoma, leukemia and certain allied and miscellaneous disorders. J Am Med Assoc. 1946;132:126–32.PubMedGoogle Scholar
  119. 119.
    Justin-Besancon L, Laville C. Antiemetic action of metoclopramide with respect to apomorphine and hydergine. C R Seances Soc Biol Fil. 1964;158:723–7.PubMedGoogle Scholar
  120. 120.
    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:v232–43.PubMedGoogle Scholar
  121. 121.
    Ho CM, et al. Dexamethasone has a central antiemetic mechanism in decerebrated cats. Anesth Analg. 2004;99:734–9.PubMedGoogle Scholar
  122. 122.
    Suzuki T, et al. Inhibitory effect of glucocorticoids on human-cloned 5-hydroxy- tryptamine3A receptor expressed in xenopus oocytes. Anesthesiology. 2004;101:660–5.PubMedGoogle Scholar
  123. 123.
    Navari RM, Gray SE, Kerr AC. Olanzapine versus aprepitant for the prevention of chemotherapy-induced nausea and vomiting: a randomized phase III trial. J Support Oncol. 2011;9:188–95.PubMedGoogle Scholar
  124. 124.
    Herrstedt J, Summers YJ, Daugaard G et al. The dopamine D2/D3 receptor antagonist APD421 in combination with ondansetron effectively prevents acute cisplatin-induced nausea and vomiting (CINV). Ann Oncol. 2012;23(suppl 9):ix507.Google Scholar
  125. 125.
    Kaiser R, Sezer O, Papies A, et al. Patient-tailored antiemetic treatment with 5- hydroxytryptamine type 3 receptor antagonists according to cytochrome P-450 2D6 genotypes. J Clin Oncol. 2003;20:2805–11.Google Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Pernille H. Hansen
    • 1
  • Jesper Palshof
    • 2
  • Jørn Herrstedt
    • 3
  1. 1.Laboratory of Neuropsychiatry/Molecular Neuropharmacology Laboratory, Department of Neuroscience and PharmacologyUniversity of CopenhagenCopenhagenDenmark
  2. 2.Department of Oncology, Herlev HospitalUniversity of CopenhagenCopenhagenDenmark
  3. 3.Department of OncologyOdense University Hospital, and University of Southern DenmarkOdense CDenmark

Personalised recommendations