Skip to main content
SpringerLink
Log in

Antiemetic Drugs: Essential Pharmacology

  • Conference paper
Antiemetics in the Supportive Care of Cancer Patients

Part of the book series: ESO Monographs ((ESO MONOGRAPHS))

  • 82 Accesses

Abstract

Development of successful agents and strategies for control of chemotherapy-induced emesis has resulted from a combination of deduction and serendipity. Elucidation of the mechanism of action of various antiemetic agents has led to a better understanding of the physiology upon which the emetic reflex arc is based and this in turn has led to the development of more selective agents with greater efficacy and an improved efficacy/toxicity ratio. However, development of various routes and schedules for antiemetic delivery has also been driven by practical considerations and convenience, and some of the greatest advances have resulted from the lack of selectivity of various antiemetic agents and the resultant identification of additional relevant mechanisms and pathways to serve as targets for antiemetic blockade.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Van Wijngaarden I, Tulp MTM, Soudijn W: The concept of selectivity in 5-HT receptor research. Eur J Pharmacol 1990 (188):301–312

    Article  PubMed  Google Scholar 

  2. Pritchard JF: Ondansetron metabolism and pharmacokinetics. Semin Oncol 1992 (19 Suppl 10):9–15

    PubMed  CAS  Google Scholar 

  3. Bigaud M, Elands J, Kastner PR, Bohnke RA, Emmert LW, Galvan M: Pharmacology of the human metabolites of dolasetron, an antiemetic 5-HT3 receptor antagonist. Drug Dev Res 1995 (34):289–296

    Article  CAS  Google Scholar 

  4. Kris MG, Grunberg SM, Gralla RJ, Baltzer L, Zaretsky SA, Lifsey D, Tyson LB, Schmidt L, Hahne WF: Dose-ranging evaluation of the serotonin antagonist dolasetron mesylate in patients receiving high-dose cisplatin. J Clin Oncol 1994 (12):1045–1049

    PubMed  CAS  Google Scholar 

  5. Colthup PV, Felgate CC, Plamer JL, Scully NL: Determination of ondansetron in plasma and its pharmacokinetics in the young and elderly. J Pharm Sci 1991 (80):868–871

    Article  PubMed  CAS  Google Scholar 

  6. Pritchard JF, Bryson JC, Kernodle AE, Benedetti TL, Powell JR: Age and gender effects on ondansetron pharmacokinetics: evaluation of healthy aged volunteers. Clin Pharmacol Ther 1992 (51):51–55

    Article  PubMed  CAS  Google Scholar 

  7. Lee CR, Plosker GL, McTavish D: Tropisetron — a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential as an antiemetic. Drugs 1993 (46):925–943

    Article  PubMed  CAS  Google Scholar 

  8. Addelman M, Erlichman C, Fine S, Warr D, Murray C: Phase I/II trial of granisetron: a novel 5-hydroxytryptamine antagonist for the prevention of chemotherapy-induced nausea and vomiting. J Clin Oncol 1990(8):337–341

    PubMed  CAS  Google Scholar 

  9. Grunberg SM, Stevenson LL, Russell CA, McDermed JE: Dose ranging phase I study of the serotonin antagonist GR38032F for prevention of cisplatin-induced nausea and vomiting. J Clin Oncol 1989 (7):1137–1141

    PubMed  CAS  Google Scholar 

  10. Marty M, d’Allens H and Groupe Multicentrique Français: Etude randomisée en double-insu comparant l’efficacité de l’ondansetron selon deux modes d’administration: injection unique et perfusion continue. Cahiers Cancer 1990 (2):541–546

    Google Scholar 

  11. Beck TM, Hesketh PJ, Madajewicz S et al: Stratified, randomized, double-blind comparison of intravenous ondansetron administered as a multiple-dose regimen versus two single-dose regimens in the prevention of cisplatin-induced nausea and vomiting. J Clin Oncol 1991 (10):1969–1975

    Google Scholar 

  12. Cubeddu LX, Hoffman IS, Fuenmayor NT, Finn AL: Efficacy of ondansetron (GR38032F) and the role of serotonin in cisplatin-induced nausea and vomiting. N Engl J Med 1990 (322):810–816

    Article  PubMed  CAS  Google Scholar 

  13. Grunberg SM, Lane M, Lester EP, Sridhar KS, Mortimer J, Murphy W, Sanderson PE: Randomized double-blind comparison of three dose levels of intravenous ondansetron in the prevention of cisplatin-induced emesis. Cancer Chemother Pharmacol 1993 (32):268–272

    Article  PubMed  CAS  Google Scholar 

  14. Navari RM, Kaplan HG, Gralla RJ, Grunberg SM, Palmer R, Fitts D: Efficacy and safety of granisetron, a selective 5-hydroxytryptamine-3 receptor antagonist, in the prevention of nausea and vomiting induced by high-dose cisplatin. J Clin Oncol 1994(12):2204–2210

    PubMed  CAS  Google Scholar 

  15. Taylor WB, Simpson JM, Bateman DN: High-dose metoclopramide by infusion: a double-blind study of plasma concentration-effect relationships in patients receiving cancer chemotherapy. Eur J Clin Pharmacol 1987 (33):161–165

    Article  PubMed  CAS  Google Scholar 

  16. Carr BI, Morgan R, Doroshow JH, Raschko J, Leong L, Margolin K, Somlo A, Akman S: Phase I clinical study of 24 hr continuous infusion prochlorperazine (compazine). Proc Am Soc Clin Oncol 1990 (9):324

    Google Scholar 

  17. Fraschini G, Ciociola A, Esparza L, Templeton D, Holmes FA, Walters RS, Hortobagyi GN: Evaluation of three oral dosages of ondansetron in the prevention of nausea and emesis associated with cyclophosphamide-doxorubicin chemotherapy. J Clin Oncol 1991 (9):1268–1274

    PubMed  CAS  Google Scholar 

  18. Hacking A: Oral granisetron — simple and effective: a preliminary report. Eur J Cancer 1992 (28A Suppl 1): S28–S32

    Article  PubMed  Google Scholar 

  19. Eglen RM, Lee CH, Smith WL, Johnson LG, Whiting RL, Hedge SS: RS 42358–197, a novel and potent 5-HT3 receptor antagonist, in vitro and in vivo. J Pharmacol Exp Ther 1993 (266):535–543

    PubMed  CAS  Google Scholar 

  20. Fernández AG, Puig J, Beleta J, Doménech T, Bou J, Berga P, Gristwood RW, Roberts DJ: Pancopride, a potent and long-acting 5-HT3 receptor antagonist, is orally effective against anticancer drug-evoked emesis. Eur J Pharmacol 1992 (222):257–264

    Article  PubMed  Google Scholar 

  21. Bateman DN, Kahn C, Davies DS: The pharmacokinetics of metoclopramide in man with observations in the dog. Br J Clin Pharmacol 1980 (9):371–377

    PubMed  CAS  Google Scholar 

  22. Taylor WB and Bateman DN: Oral bioavailability of high-dose metoclopramide. Eur J Clin Pharmacol 1986(31):41–44

    Article  PubMed  CAS  Google Scholar 

  23. Saynor DA and Dixon CM: The metabolism of ondansetron. Eur J Cancer Clin Oncol 1989 (25 Suppl 1): S75–S77

    PubMed  CAS  Google Scholar 

  24. Cupissol D, Bressolle F, Adenis L, Carmichael J, Bessell E, Allen A, Wargenau M, Romain D: Evaluation of the bioequivalence of tablet and capsule formulations of granisetron in patients undergoing cytotoxic chemotherapy for malignant disease. J Pharm Sci 1993 (82):1281–1284

    Article  PubMed  CAS  Google Scholar 

  25. Taylor WB and Bateman DN: Preliminary studies of the pharmacokinetics and pharmacodynamics of prochlorperazine in healthy volunteers. Br J Clin Pharmacol 1987 (23):137–142

    PubMed  CAS  Google Scholar 

  26. Wall ME, Sadler BM, Brine D, Taylor H, Parez-Reyes M: Metabolism, disposition, and kinetics of delta-9-tetrahydrocannabinol in men and women. Clin Pharmacol Ther 1983 (34):352–363

    Article  PubMed  CAS  Google Scholar 

  27. Tyson LB, Gralla RJ, Kris MG, Young CS, Clark RA: Dose-ranging antiemetic trial of high-dose oral metoclopramide. Am J Clin Oncol 1989 (12):239–243

    Article  PubMed  CAS  Google Scholar 

  28. Morrow GR, Lindke JL, Black PM: Predicting development of anticipatory nausea in cancer patients: prospective examination of eight clinical characteristics. J Pain Symptom Manage 1991 (6):215–223

    Article  PubMed  CAS  Google Scholar 

  29. Mattes RD, Shaw LM, Edling-Owens J, Engelman K, Elsohly MA: Bypassing the first-pass effect for the therapeutic use of cannabinoids. Pharmacol Bio-chem Behav 1993 (44):745–747

    Article  CAS  Google Scholar 

  30. Nahas GG: Current status of marijuana research. JAMA 1979 (242):2775–2778

    Article  PubMed  CAS  Google Scholar 

  31. Vinciguerra V, Moore T, Brennan E: Inhalation marijuana as an antiemetic for cancer chemotherapy. NY State J Med 1988 (88):525–527

    CAS  Google Scholar 

  32. Patterson WK and Keane PW: Use of the buccal route for the administration of an antiemetic. Anesth Analg 1992(74):937–938

    Article  PubMed  CAS  Google Scholar 

  33. Clissold SP and Heel RC: Transdermal hyoscine (scopolamine) — a preliminary review of its pharmacodynamic properties and therapeutic efficacy. Drugs 1985 (29):189–207

    Article  PubMed  CAS  Google Scholar 

  34. Meyer BR, O’Mara V, Reidenberg MM: A controlled clinical trial of the addition of transdermal scopolamine to a standard metoclopramide and dexametha-sone antiemetic regimen. J Clin Oncol 1987 (5): 1994–1997

    PubMed  CAS  Google Scholar 

  35. Calpena AC, Blanes C, Moreno J, Obach R, Domenech J: A comparative in vitro study of transdermal absorption of antiemetics. J Pharm Sci 1994 (83):29–33

    Article  PubMed  CAS  Google Scholar 

  36. Kobrinsky NL, Pruden PB, Cheang MS, Levitt M, Bishop AJ, Tenenbein M: Increased nausea and vomiting induced by naloxone in patients receiving cancer chemotherapy. Am J Pediatr Hematol Oncol 1988(10):206–208

    Article  PubMed  CAS  Google Scholar 

  37. Barnes NM, Bunce KT, Naylor RJ, Rudd JA: The actions of fentanyl to inhibit drug-induced emesis. Neuropharmacology 1991 (30):1073–1083

    Article  PubMed  CAS  Google Scholar 

  38. Perry MR, Rhee J, Smith WL: Plasma levels of peptide YY correlate with cisplatin-induced emesis in dogs. J Pharm Pharmacol 1994 (46):553–557

    Article  PubMed  CAS  Google Scholar 

  39. Yaksh TL, Jessell TM, Gamse R, Mudge AW, Leeman SE: Intrathecal morphine inhibits substance P release from mammalian spinal cord in vivo. Nature 1980 (286):155–157

    Article  PubMed  CAS  Google Scholar 

  40. Andrews PLR and Bhandari P: Resinferatoxin, an ultrapotent capsaicin analogue, has antiemetic properties in the ferret. Neuropharmacology 1993 (32):799–806

    Article  PubMed  CAS  Google Scholar 

  41. Bountra C, Bunce K, Dale T, Gardner C, Jordan C, Twissell D, Ward P: Antiemetic profile of a non-peptide neurokinin NK1 receptor antagonist, CP-99,994, in ferrets. Eur J Pharmacol 1993 (249):R3–4

    Article  PubMed  CAS  Google Scholar 

  42. Blum K, Noble EP, Sheridan PJ et al: Allelic association of human dopamine D2 receptor gene in alcoholism. JAMA 1990 (263):2055–2060

    Article  PubMed  CAS  Google Scholar 

  43. Cloninger CR: D2 dopamine receptor gene is associated but not linked with alcoholism. JAMA 1991 (266):1833–1834

    Article  PubMed  CAS  Google Scholar 

  44. Noble EP, Blum K, Ritchie T, Montgomery A, Sheridan PJ: Allelic association of the D2 dopamine receptor gene with receptor binding characteristics in alcoholism. Arch Gen Psychiatry 1991 (48):648–654

    PubMed  CAS  Google Scholar 

  45. Wise RA and Rompre PP: Brain dopamine and reward. Ann Rev Psychol 1989 (40):191–225

    Article  CAS  Google Scholar 

  46. Sullivan JR, Leyden MJ, Bell R: Decreased cisplatin induced nausea and vomiting with alcohol ingestion. N Engl J Med 1983 (309):796

    PubMed  CAS  Google Scholar 

  47. D’Acquisto RW, Tyson LB, Gralla RJ, Clark RA, Kris MG, Von Witte DM, Cacavio A: The influence of a chronic high alcohol intake on chemotherapy-induced nausea and vomiting. Proc Am Soc Clin Oncol 1985 (5):257

    Google Scholar 

  48. Hesketh PJ, Murphy WK, Lester EP et al: GR38032F (GR-C507/75): a novel compound effective in the prevention of acute cisplatin-induced emesis. J Clin Oncol 1989 (7):700–705

    PubMed  CAS  Google Scholar 

  49. Wong DT, Reid LR, Li TK, Lumeng L: Greater abundance of serotonin1A receptor in some brain areas of alcohol-preferring rats compared to non-preferring rats. Pharmacol Biochem Behav 1993 (46):173–177

    Article  PubMed  CAS  Google Scholar 

  50. Manrique C, Segu L, Héry F, Héry M, Faudon M, Franois-Bellan AM: Increase of central 5-HT1B binding sites following 5,7-dihydroxytryptamine axotomy in the adult rat. Brain Res 1993 (623):345–348

    Article  PubMed  CAS  Google Scholar 

  51. Pandey SC, Dubey MP, Piano MR, Schwertz DW, Davis JM, Pandey GN: Modulation of 5-HT1C receptors and phosphoinositide system by ethanol consumption in rat brain and choroid plexus. Eur J Pharmacol 1993 (247):81–88

    Article  PubMed  CAS  Google Scholar 

  52. Srikiatkhachorn A, Govitrapong P, Limthavon C: Up-regulation of 5-HT2 serotonin receptor: a possible mechanism of transformed migraine. Headache 1994(34):8–11

    Article  PubMed  CAS  Google Scholar 

  53. Brann, MR: Serotonin-S2 and dopamine-D2 receptors are the same size in membranes. Biochem Biophys Res Commun 1985 (133):1181–1186

    Article  PubMed  CAS  Google Scholar 

  54. Ray SK and Poddar MK: Interaction of central serotonin and dopamine in the regulation of carbaryl-induced tremor. Eur J Pharmacol 1990 (181): 159–166

    Article  PubMed  CAS  Google Scholar 

  55. Kelland MD, Freeman AS, Chiodo LA: Serotonergic afferent regulation of the basic physiology and pharmacological responsiveness of nigrostriatal dopamine neurons. J Pharmacol Exp Ther 1990 (253):803–811

    PubMed  CAS  Google Scholar 

  56. Schmidt CJ, Taylor VL, Abbate GM, Nieduzak TR: 5-HT2 antagonists stereoselectively prevent the neurotoxicity of 3,4-methylenedioxymethampheta-mine by blocking the acute stimulation of dopamine synthesis: reversal by L-dopa. J Pharmacol Exp Ther 1991 (256):230–235

    PubMed  CAS  Google Scholar 

  57. Zhou FC, Bledsoe S, Murphy J: Serotonergic sprouting is induced by dopamine-lesion in substantia nigra of adult rat brain. Brain Res 1991 (556):108–116

    Article  PubMed  CAS  Google Scholar 

  58. Hagan RM, Butler A, Hill JM, Jordan CC, Ireland SJ, Tyers MB: Effect of the 5-HT3 receptor antagonist, GR38032F, on responses to injection of a neurokinin agonist into the ventral tegmental area of the rat brain. Eur J Pharmacol 1987 (138):303–305

    Article  PubMed  CAS  Google Scholar 

  59. Power RF, Lydon JP, Conneely OM, O’Malley BW: Dopamine activation of an orphan of the steroid receptor superfamily. Science 1991 (252):1546–1548

    Article  PubMed  CAS  Google Scholar 

  60. Rawdon BB and Andrew A: Distribution of serotonin-immunoreactive gut endocrine cells in mice: differential effects on the sensitivity to 5-MeODMT, 8-OH-DPAT and 5-HTP as measured by two nociceptive tests. Brain Res 1988 (440):42–52

    Article  Google Scholar 

  61. Eide PK and Hole K: The role of 5-hydroxytryp-tamine (5-HT) receptor subtypes and plasticity in the 5-HT systems in the regulation of nociceptive sensitivity. Cephalalgia 1993 (13):75–85

    Article  PubMed  CAS  Google Scholar 

  62. Eschalier A, Kayser V, Guilbaud G: Influence of a specific 5-HT3 antagonist on carrageenan-induced hyperalgesia in rats. Pain 1989 (36):249–255

    Article  PubMed  CAS  Google Scholar 

  63. Alhaider AA, Lei SZ, Wilcox GL: Spinal 5-HT3 receptor-mediated antinociception: possible release of GABA. J Neurosci 1991 (11):1881–1888

    PubMed  CAS  Google Scholar 

  64. Campbell M and Bateman DN: Pharmacokinetic optimisation of antiemetic therapy. Clin Pharmaco-kinet 1992 (23): 147–160

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Vermont Cancer Center, University of Vermont, Fletcher Allen Health Care, 111 Colchester Avenue - Patrick 534, Burlington, VT, 05401-1429, USA

    Steven M. Grunberg

Authors
  1. Steven M. Grunberg
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Medical Oncology Division, Policlinico Monteluce, Via Brunamonti, 06122, Perugia, Italy

    Maurizio Tonato M.D.

Rights and permissions

Reprints and permissions

Copyright information

© 1996 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Grunberg, S.M. (1996). Antiemetic Drugs: Essential Pharmacology. In: Tonato, M. (eds) Antiemetics in the Supportive Care of Cancer Patients. ESO Monographs. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-80240-9_3

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-80240-9_3

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-80242-3

  • Online ISBN: 978-3-642-80240-9

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation