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Drugs

, Volume 42, Issue 4, pp 551–568 | Cite as

5-HT3 Receptor Antagonists

An Overview of their Present Status and Future Potential in Cancer Therapy-Induced Emesis
  • Matti S. Aapro
Review Article

Summary

The serotonin (5-hydroxytryptamine, 5-HT) antagonists, which bind at the type 3 receptor (5-HT3 receptor), have been evaluated in several preclinical models and found to be effective in alleviating cancer therapy-related emesis. The antiemetic efficacy of ondansetron (GRF-38032F, odanserin), granisetron (BRL-43694), tropisetron (ICS-205930), MDL-72222 and MDL-73147EF, batanopride (BMY-25801-01) and several others is at various stages of investigation. Ondansetron is currently marketed in several countries and the same will soon be true for granisetron.

At this stage it is not yet possible to evaluate the comparative efficacy of each of these compounds, although recent preclinical data reveal some differences in the affinity of these compounds for other receptors. Side effects related to these agents have been minor, consisting mainly of slight headaches; possible rises in liver enzymes related to some compounds need further evaluation. Future studies will need to determine the exact role of 5-HT3 antagonists, although their cost may confine their use to patients at high risk for side effects from metoclopramide.

Keywords

Ondansetron Metoclopramide Granisetron Antiemetic Efficacy Antiemetic Activity 
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.

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References

  1. Aapro MS. A new class of antiemetics: the serotonin (5HT3) antagonists. (In Spanish.) Revisiones en Cancer 3: 134–137, 1989Google Scholar
  2. Aapro MS. Present role of corticosteroids. In Senn HJ & Glaus A (Eds) Supportive care in cancer patients II. Recent results in cancer research, Vol. 121, pp. 91–100, Springer-Verlag, Berlin Heidelberg, 1991CrossRefGoogle Scholar
  3. Aapro MS, Huber P, Manghani K, Crenshaw RR, Schwartz SE. BMY-25801-01 (BMY): a novel antiemetic to prevent cisplatin induced nausea and vomiting. Proceedings of the American Society of Clinical Oncology 6: 272, 1987Google Scholar
  4. 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. Journal of Clinical Oncology 8: 337–341, 1990PubMedGoogle Scholar
  5. Anderson JV, Coupe MO, Morris JA, Hodgson HJF, Bloom SR. Remission of symptoms in carcinoid syndrome with a new 5-hydroxytryptamine M receptor antagonist. British Medical Journal 294: 1129, 1987PubMedCrossRefGoogle Scholar
  6. Andrews PLR, Davis CJ, Bingham S, Davidson GHS, Hawthorn J, et al. The abdominal visceral innervation and the emetic reflex: pathways, pharmacology, and plasticity. Canadian Journal of Physiology and Pharmacology 68: 325, 1990PubMedCrossRefGoogle Scholar
  7. Andrews PLR, Hawthorn J. Evidence for an extra-abdominal site of action for the 5-HT receptor antagonist BRL 24924 in the inhibition of radiation evoked emesis in the ferret. British Journal of Pharmacology 88: 497–499, 1987Google Scholar
  8. Baltzer L, Kris MG, Tyson LB, Rigas JR, Pisters KMW, et al. Dose ranging antiemetic study of the serotonin antagonist RG 12915. Abstract 1207. Proceedings of the American Society of Clinical Oncology 10: 341, 1991Google Scholar
  9. Barnes NB, Costall B, Naylor RJ. [3H]-Zacopride identifies 5-HT3 binding sites in rat entorrhinal cortex. British Journal of Pharmacology 94: 391P, 1988Google Scholar
  10. Barnes NM, Ge J, Naylor RJ, Rudd JA. Cisplatin induced emesis: preliminary results indicative of changes in plasma levels of 5-hydroxytryptamine. British Journal of Cancer 62: 862–864, 1990PubMedCrossRefGoogle Scholar
  11. Basurto C, Roila F, Bracarda S, Picciafuoco M, Patoia L, et al. Antiemetic activity and tolerability of metoclopramide (MIC) vs dexamethasone (DES) vs placebo (PL) for prevention of delayed emesis from cisplatin (CDDP) chemotherapy: a randomized single-blind cross-over study. Abstract 1316. Proceedings of the American Society of Clinical Oncology 8: 338, 1989Google Scholar
  12. Bermudez J, Boyle EA, Miner WD, Sanger GJ. The anti-emetic potential of the 5-hydroxytryptamine3 receptor antagonist BRL 43694. British Journal of Cancer 58: 644–650, 1988PubMedCrossRefGoogle Scholar
  13. Bianchi C, Beani L, Crema C. Effects of metoclopramide on isolated guinea-pig colon. European Journal of Pharmacology 12: 332–341, 1970PubMedCrossRefGoogle Scholar
  14. Blackwell CP, Harding SM. The clinical pharmacology of ondansetron. European Journal of Cancer and Clinical Oncology 25 (Suppl. 1): S21-S24, 1989Google Scholar
  15. Bleiberg H, Dodion P, Piccart M, Lips S, Janssens N, et al. Randomized double-blind crossover evaluation of batanopride (BMY-25801) vs placebo in patients receiving high-dose cisplatin. Abstract 1307. Proceedings of the American Society of Clinical Oncology 9: 338, 1990Google Scholar
  16. Blijham G, Dott C, on behalf of the Granisetron Study Group. A study to assess the efficacy and safety of the use of granisetron (G), a selective 5HT3 antagonist, for treatment of chemotherapy induced emesis in patients receiving multiple cycles of cytotoxic therapy. Abstract W9:4. XVth Congress of the ESMO, Copenhagen, 1990Google Scholar
  17. Blower PR. The role of specific 5-HT3 receptor antagonism in the control of cytostatic drug-induced emesis. European Journal of Clinical Oncology 26 (Suppl. 1): S8-S11, 1990Google Scholar
  18. Blumer JL, Shurin S, Patrick S, Pritchard JF. Evaluation of pharmacokinetics, safety, and efficacy of ondansetron in children receiving chemotherapy. Abstract 1284. Proceedings of the American Society of Clinical Oncology 9: 332, 1990Google Scholar
  19. Bockaert J, Sebben M, Dumuis A. Pharmacological characterization of 5-hydroxytryptamine4(5-HT4) receptors positively coupled to adenylate cyclase in adult guinea pig hippocampal membranes: effect of substituted benzamide derivatives. Molecular Pharmacology 37: 408–411, 1990PubMedGoogle Scholar
  20. Bonneterre J, Chevallier B, Metz R, Fargeot P, Pujade-Lauraine E, et al. A randomized double-blind comparison of ondansetron and metoclopramide in the prophylaxis of emesis induced by cyclophosphamide, fluorouracil, and doxorubicin or epirubicin chemotherapy. Journal of Clinical Oncology 8: 1063–1069, 1990PubMedGoogle Scholar
  21. Bowman A, Allan SG, Leonard RCF, Scully N, Challoner T, et al. The pharmacokinetics and antiemetic efficacy of the 5-HT3 antagonist GR38032F (GR) at different doses and schedules in cisplatinum (CP) induced emesis. Abstract 249. Cancer Chemotherapy and Pharmacology 23 (Suppl.), 1988Google Scholar
  22. Boyle EA, Miner WD, Sanger GJ. Antiemetic activity of BRL 43694, a novel 5-HT3 receptor antagonist. British Journal of Cancer 56: 227, 1987Google Scholar
  23. Bradley PB, Engel G, Fenuik W, Fozard JR, Humphrey PBA, et al. Proposals for the classification and nomenclature of functional receptors for 5-hydroxy-tryptamine. Neuropharmacology 25: 563–576, 1986PubMedCrossRefGoogle Scholar
  24. Brady ME, Dandekar KA, Aapro MS, Schwartz SE. Pharmacokinetics of a novel antiemetic, BMY-25801, in cancer patients following intravenous infusion. Abstract 292. Proceedings of the Fourth European Conference on Clinical Oncology, Madrid, November 1–4, 1987Google Scholar
  25. Bregni M. Siena S, Di Nicola M, Bonadonna G, Gianni AM. Tropisetron plus haloperidol to ameliorate nausea and vomiting associated with high-dose alkylating agent cancer chemotherapy, European Journal of Cancer 27: 561–565, 1991Google Scholar
  26. Bremer K, Smit P, on behalf of the Granisetron Study Group. Granisetron (G) compared to a combination of alizapride (A) plus dexamethasone (D) for the prophylaxis and control of cytotoxic induced emesis over 5 days. Abstract W9:3. XVth ESMO Congress, Copenhagen, 1990Google Scholar
  27. Bryson JC, Finn AL, Plagge PB, Twaddell TPH, Brenckman Jr WD. The safety profile of iv ondansetron from clinical trials. Abstract 1268. Proceedings of the American Society of Oncology 9: 328, 1990Google Scholar
  28. Bunce K, Tyers M, Beranek P. Clinical evaluation of 5-HT3 receptor antagonists as anti-emetics. Trends in Pharmacological Sciences 12: 46–48, 1991PubMedCrossRefGoogle Scholar
  29. Buser K, Joss R, Piguet D, Aapro M, Cavalli F, et al. A randomized, double-blind comparison of oral ondansetron and placebo in the prophylaxis of CMF-induced nausea and vomiting. Abstract 1279. Proceedings of the American Society of Clinical Oncology 9: 331, 1990Google Scholar
  30. Butler A, Hill JM, Ireland SJ, Jordan CC, Tyers MB. Pharmacological properties of GR38032F, a novel antagonist at 5-HT3 receptors. British Journal of Pharmacology 94: 397–412, 1988PubMedCrossRefGoogle Scholar
  31. Carden PA, Mitchell SL, Waters KD, Tiedemann K, Ekert H. Prevention of cyclophosphamide/cytarabine-induced emesis with ondansetron in children with leukemia. Journal of Clinical Oncology 8: 1, 1990Google Scholar
  32. Carmichael J, Cantwell BMJ, Edwards CM, Rapeport WG, Harris AL. The serotonin type 3 receptor antagonist BRL 43694 and nausea and vomiting induced by cisplatin. British Medical Journal 297: 110–111, 1988PubMedCrossRefGoogle Scholar
  33. Cassidy J, Raina V, Lewis C, Adams L, Soukop M, et al. Pharmacokinetics and anti-emetic efficacy of BRL43694, a new selective 5HT-3 antagonist. British Journal of Cancer 58: 651–653, 1988PubMedCrossRefGoogle Scholar
  34. Catimel G, Clavel M, Gignoux B, Bregman B, Goodlow J, et al. Randomized double-blind crossover placebo-controlled trial of batanopride (BMY-25801) in patients receiving high-dose cisplatin. Abstract 1249. Proceedings of the American Society of Clinical Oncology 9: 323, 1990Google Scholar
  35. Chase BJ, Martin GE. Action of the novel 5HT-3 antagonist RG 12915 in blocking serotonin-induced contractions of guinea pig ileum. FASEB Journal 4: A476, 1990Google Scholar
  36. Chevallier B. on behalf of the Granisetron Study Group. Efficacy and safety of granisetron compared with high-dose metoclo-pramide plus dexamethasone in patients receiving high-dose cisplatin. European Journal of Cancer 26 (Suppl. 1): S33–S36, 1990PubMedCrossRefGoogle Scholar
  37. Clark RA, Kris MG, Gralla JR, Tyson LB. Serotonin antagonists demonstrate antiemetic (AE) effectiveness without extrapyramidal symptoms: analysis of studies with 3 new agents in 155 patients (pts). Abstract 1246. Proceedings of the American Society of Clinical Oncology 9: 322, 1990Google Scholar
  38. Clavel M, Klein T, Metz R, et al. A randomised, comparative study of the anti-emetic effect and safety of MDL 72,222 and ’standard anti-emetic therapy’ in patients receiving cisplatin-containing chemotherapy for malignant tumors. Cancer Communication 3: 63, 1989Google Scholar
  39. Cohen ML, Bloomquist W, Gidda JS, Lacefield W. LY277359 maleate: a potent and selective 5-HT3 receptor antagonist without gastroprokinetic activity. Journal of Pharmacology and Experimental Therapeutics 254: 350–355, 1990PubMedGoogle Scholar
  40. Costall B, Domeney AM, Gunning SJ, Naylor RJ, Tattersall FD, et al. GR38032F: a potent and hovel inhibitor of cisplatin-induced emesis in the ferret. British Journal of Pharmacology 90: 90P, 1987Google Scholar
  41. Costall B, Domeney AM, Naylor RJ, Tattersall FD. 5-Hydroxytryptamine M-receptor antagonism to prevent cisplatin-induced emesis. Neuropharmacology 25: 959–961, 1986PubMedCrossRefGoogle Scholar
  42. Costall B, Naylor RJ, Tyers MB. Recent advances in the neuropharmacology of 5-HT3 agonists and antagonists. Reviews in the Neurosciences 2: 41–65, 1988Google Scholar
  43. Coupe M. Adverse reaction to 5-HT3 antagonist ICS 205-930. Lancet 1: 1494, 1987PubMedCrossRefGoogle Scholar
  44. Craig DA, Clarke DE. Pharmacological characterization of a neuronal receptor for 5-hydroxytryptamine in guinea pig ileum with properties similar to the 5-hydroxytryptamine4 receptor. Journal of Pharmacology and Experimental Therapeutics 252: 1378–1386, 1990PubMedGoogle Scholar
  45. Craig DA, Eglen RM, Walsh LKM, Perkins LA, Whiting RL, et al. 5-methoxytryptamine and 2-methyl-5-hydroxytryptamine-induced desensitization as a discriminative tool for the 5-HT3 and putative 5-HT4 receptors in guinea pig ileum. Naunyn-Schmiedeberg’s Archives of Pharmacology 342: 9–16, 1990PubMedGoogle Scholar
  46. Cubeddu LX, Hoffmann IS, Fuenmayor NT, Finn AL. Efficacy of ondansetron (GR38032F) and the role of serotonin in cisplatin-induced nausea and vomiting. New England Journal of Medicine 322: 810–816, 1990PubMedCrossRefGoogle Scholar
  47. Cunningham D, Pople A, Ford HT, Hawthorn J, Gazet JC, et al. Prevention of emesis in patients receiving cytotoxic drugs by GR38032F, a selective 5-HT3 receptor antagonist. Lancet 1: 1461–1462, 1987PubMedCrossRefGoogle Scholar
  48. Cunningham D, Turner A, Hawthorn J, et al. Ondansetron with and without dexamethasone to treat chemotherapy induced emesis. Lancet 1: 1323–1324, 1989PubMedCrossRefGoogle Scholar
  49. Cupissol DR, Serrou B, Caubel M. The efficacy of granisetron as a prophylactic antiemetic and intervention agent in high-dose cisplatin-induced emesis. European Journal of Cancer 26 (Suppl. 1);S23-S27, 1990Google Scholar
  50. Davis MA, Martin GE. Potent antagonism of the von Bezold Jarisch effect by the novel 5HT-3 antagonist RG 12915. FASEB Journal 4: A475, 1990Google Scholar
  51. de Mulder PHM, Seynaeve C, Vermorken JB, van Liessum PA, Mols-Jevdevic S, et al. Ondansetron compared with high-dose metoclopramide in prophylaxis of acute and delayed cisplatin-induced nausea and vomiting. Annals of Internal Medicine 113: 834–840, 1990PubMedGoogle Scholar
  52. Dogliotti L, Faggiuolo R, Berruti A, Antonacci RA, Ortega C, et al. Prevention of nausea and vomiting in cisplatin-treated patients by a selective 5-hydroxytryptamine (5-HT3) receptor antagonist, ICS 205-930. Tumori 76(6): 595–598, 1990PubMedGoogle Scholar
  53. Dumuis A, Sebben M, Bockaert J. BRL 24924: a potent agonist at a non-classical 5-HT receptor positively coupled with adenylate cyclase in colliculi neurons. European Journal of Pharmacology 162: 381–384, 1989PubMedCrossRefGoogle Scholar
  54. Dumuis A, Sebben M, Bockaert J. The gastrointestinal prokinetic benzamine derivatives are agonists at the non-classical 5-HT receptor (5-HT4) positively coupled to adenylate cyclase in neurons. Naunyn-Schmiedeberg’s Archives of Pharmacology 340: 403–410, 1990Google Scholar
  55. Dunbar AW, McClelland CM, Sanger GJ. BRL 24924: a stimulant of gut motility which is also a potent antagonist of the Bezold-Jarisch reflex in anaesthetised rats. British Journal of Pharmacology 88: 319P, 1986Google Scholar
  56. Dunlop DJ, Young F, Soukop M, Murdoch R, Upward J. The inhibition of 5-HT induced axon-reflex flare in patients undergoing treatment with granisetron (kytril) by prophylaxis and intervention for cancer chemotherapy induced nausea and vomiting. Abstract W9:7. XVth ESMO Congress, Copenhagen, 1990Google Scholar
  57. Fake CS, King FD, Sanger GJ. BRL43694: a potent and novel 5-HT3 receptor antagonist. British Journal of Pharmacology 91: 335P, 1987Google Scholar
  58. Fitzpatrick LR, Lambert RM, Pendley CE, Martin GE, Bostwick JS, et al. A potent 5-hydroxytryptamine-3 antagonist that is an orally effective inhibitor of cytotoxic drug-induced emesis in the ferret and dog. Journal of Pharmacology and Experimental Therapeutics 254: 450–455, 1990PubMedGoogle Scholar
  59. Fludzinski P, Evrard DA, Bloomquist WE, Lacefield WB, Pfeifer W, et al. Indazoles as indple bioisosteres: synthesis and evaluation of the tropanyl ester and amide of indazole-3-carboxylate as antagonists at the serotonin 5HT3 receptor. Journal of Medicinal Chemistry 30: 73–80, 1987CrossRefGoogle Scholar
  60. Fontaine J, Reuse JJ, Pharmacological analysis of the effects of metoclopramide on the guinea-pig ileum in vitro Archives Internationales de Pharmacodynamie et de Therapie 204: 293–305, 1973PubMedGoogle Scholar
  61. Fozard JR. Basic mechanisms of antimigraine drugs. In Critchley M et al. (Eds) Advances in Neurology 33: 295–307, Raven Press, New York, 1982Google Scholar
  62. Fozard JR. MDL-72222: a potent and highly selective antagonist at neuronal 5-hydroxytryptamine receptors. Naunyn-Schmiedeberg’s Archives of Pharmacology 326: 36–44, 1984PubMedCrossRefGoogle Scholar
  63. Gaddum JH, Picarelli ZP. Two kinds of tryptamine receptor. British Journal of Pharmacology 9: 323, 1957Google Scholar
  64. Gandara DR, Harvey WH, Monaghan GG, Bryson JC, Finn AL. Efficacy of ondansetron in the prevention of delayed emesis following high dose cisplatin (DDP). Abstract 1270. Proceedings of the American Society of Clinical Oncology 9: 328, 1990Google Scholar
  65. Gittos MW, Fatmi M. MDL-73147-EF: a potent 5-HT3 receptor antagonist incorporating a novel bridged pseudopelletierene ring system. Actualités de Chimie Thérapeutique 16: 187–198, 1989Google Scholar
  66. Goddard PM, Jones M, Pollard LA, Valenti MR, Harrap KR. The 5-HT3 antagonist BRL 43694 does not compromise the efficacy of cisplatin in tumour-bearing mice. Cancer Chemotherapy and Pharmacology 25: 377–379, 1990PubMedCrossRefGoogle Scholar
  67. Gralla RJ, Itri LM, Pisko SE, Squillante SE, Kelsen DP, et al. Anti-emetic efficacy of high dose metoclopramide: randomised trials with placebo and prochlorperazine in patients with chemotherapy-induced nausea and vomiting. New England Journal of Medicine 305: 905–909, 1981PubMedCrossRefGoogle Scholar
  68. Gralla RJ, Kris MG, Tyson LB, Clark RA. Controlling emesis in patients receiving cancer chemotherapy. In Senn HJ et al. (Eds) supportive care in cancer patients. Recent results in cancer research 108, pp. 89–101, Springer-Verlag, Berlin Heidelberg, 1988CrossRefGoogle Scholar
  69. Grunberg SM, Groshen S, Robinson DC, Stevenson LL, Sanderson PE. Correlation of anti-emetic efficacy and plasma levels of ondansetron. European Journal of Cancer 26: 879–882, 1990PubMedCrossRefGoogle Scholar
  70. 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. Journal of Clinical Oncology 7: 1137–1141, 1989PubMedGoogle Scholar
  71. Gylys JA, Wright RN, Nicolosi WD, Buyniski JP, Crenshaw RR. BMY-25801, an antiemetic agent free of D2-dopamine receptor antagonist properties. Journal of Pharmacology and Experimental Therapeutics 244: 830–837, 1988PubMedGoogle Scholar
  72. Hendriks R, Bornstein JC, Furness JB. Evidence for two types of 5-hydroxytryptamine receptor on secretomotor neurons of the guinea pig ileum. Naunyn-Schmiedeberg’s Archives of Pharmacology 339: 409–414, 1989PubMedCrossRefGoogle Scholar
  73. Heron JF, on behalf of the Granisetron Study Group. Studies with oral granisetron. Presented at Advances in Emesis Control, 15th Conference of the Union Internationale Contre le Cancer, Hamburg, August, 1990Google Scholar
  74. Herrstedt J, Jeppesen BH, Domberrowsky P. Dose-limiting hypotension with the 5-HT3-antagonist batanopride (BMY-25801). Annals of Oncology 2: 154–155, 1991PubMedGoogle Scholar
  75. Hesketh PJ, Twaddell T, Finn A. A possible role for cisplatin (DDP) in the transient hepatic enzyme elevation after ondansetron administration. Abstract 1250. Proceedings of the American Society of Clinical Oncology 9: 323, 1990Google Scholar
  76. Higgins GA, Kilpatrick GJ, Bunce KT, Jones BJ, Tyers MB. 5-HT3 receptor antagonists injected in the area postrema inhibit cisplatin-induced emesis in the ferret. British Journal of Pharmacology 97: 247–255, 1989PubMedCrossRefGoogle Scholar
  77. Hunter AE, Prentice HG, Pothecary K, Coumar A, Collis C, et al. Granisetron: a selective 5-HT3 receptor antagonist for the prevention of radiation induced emesis during total body irradiation. Bone Marrow Transplantation 7(6): 439–441, 1991PubMedGoogle Scholar
  78. Jones BJ, Costall B, Domeney AM, Kelly ME, Naylor RJ, et al. The potential anxiolytic activity of GR 38032F, a 5-HT3 receptor antagonist. British Journal of Pharmacology 93: 985–993, 1988PubMedCrossRefGoogle Scholar
  79. Joss RA, Richner J, Brunner KW, Rohrbach D, Pirovino M, et al. BRL 43694: a novel antiemetic to prevent nausea and vomiting induced by chemotherapy. Journal of the National Cancer Institute 80: 1340–1341, 1988PubMedCrossRefGoogle Scholar
  80. Kaasa S, Kvaloy S, Dicato MA, Ries F, Huys JV, et al. A comparison of ondansetron with metoclopramide in the prophylaxis of chemotherapy-induced nausea and vomiting: a randomized, double-blind study. International Emesis Study Group. European Journal of Cancer 26: 311–314, 1990Google Scholar
  81. Kilpatrick GJ, Jones BJ, Tyers MB. Identification and distribution of 5-HT3 receptors in rat brain using radiological binding. Nature 330: 746–748, 1987PubMedCrossRefGoogle Scholar
  82. King GL. Emesis and defecations induced by the 5-hydroxytryptamine (5-HT3) receptor antagonist zacopride in the ferret. Journal of Pharmacology and Experimental Therapeutics 253: 1034–1041, 1990PubMedGoogle Scholar
  83. Kirchner V, Aapro M. Safety and anti-emetic effect of MDL 73.147EF, a new 5-HT3 antagonist, in cancer patients requiring cytotoxic chemotherapy. Abstract W9:12. XVth ESMO Congress, Copenhagen, 1990Google Scholar
  84. Kris MG, Gralla J, Clark RA, Tyson LB. Dose-ranging evaluation of the serotonin antagonist GR-C507/75 (GR38032F) when used as an antiemetic in patients receiving anticancer chemotherapy. Journal of Clinical Oncology 6: 659–662, 1988PubMedGoogle Scholar
  85. Kris MG, Gralla RJ, Clark RA, Tyson LB. Phase II trials of the serotonin antagonist GR38032F for the control of vomiting caused by cisplatin. Journal of the National Cancer Institute 81: 42–46, 1989bPubMedCrossRefGoogle Scholar
  86. Kris MG, Gralla RJ, Tyson LB, Clark RA, Cirrincione-Groshen S. Controlling delayed vomiting: double-blind, randomized trial comparing placebo, dexamethasone alone, and metoclopramide plus dexamethasone in patients receiving cisplatin. Journal of Clinical Oncology 7: 108–114, 1989aPubMedGoogle Scholar
  87. Leibundgut U, Lancranjan I. First results with ICS 205-930 (5-HT, receptor antagonist) in prevention of chemotherapy induced emesis. Lancet 1: 1198, 1987PubMedCrossRefGoogle Scholar
  88. Leibundgut U, Rabineau A, Obrecht JP. ICS 205-930: a 5-HT3 receptor antagonist to prevent cisplatin induced emesis. Proceedings of the American Society of Clinical Oncology 7: 100, 1988Google Scholar
  89. Lemerle J, Ameral D, Southall DP, Upward J, Murdoch RD. The efficacy and safety of granisetron, a selective 5HT3-receptor antagonist in the prevention of chemotherapy induced emesis in paediatric patients. European Journal of Cancer, in press, 1991Google Scholar
  90. Logue J, Wilkinson P, Haegele KD, Orwin J. A single-dose-finding study of the antiemetic effect and associated plasma levels of MDL 72222 in patients receiving cisplatin. Cancer Chemotherapy and Pharmacology 27: 472–476, 1991PubMedCrossRefGoogle Scholar
  91. Lucot JB. Blockade of 5-hydroxytryptamine3 receptors prevents cisplatin-induced but not motion-or xylazine-induced emesis in the cat. Pharmacology, Biochemistry and Behavior 32: 207–210, 1989CrossRefGoogle Scholar
  92. Marty M. Ondansetron in the prophylaxis of acute cisplatin-induced nausea and vomiting. European Journal of Cancer 25 (Suppl. 1): S41-S45, 1989bGoogle Scholar
  93. Marty M. on behalf of the Granisetron Study Group. A comparative study of the use of granisetron, a selective 5-HT3 antagonist, versus a standard antiemetic regimen of ehlorpromazine plus dexamethasone in the treatment of cytostatic-induced emesis. European Journal of Cancer 26 (Suppl. 1): S28–S32, 1990aPubMedGoogle Scholar
  94. Marty M, d’Aliens H, for the French Ondansetron Study Group. A single daily dose (SD) of ondansetron (OND) is as effective as a continuous infusion (CI) in the prevention of cisplatin (DDP) induced nausea (N) and vomiting (V). Abstract W9:14. XVth ESMO Congress, Copenhagen, 1990cGoogle Scholar
  95. Marty M, Droz JP, Pouillart P, Paule B, Brion N, et al. GR38032F, a 5HT3 receptor antagonist, in the prophylaxis of acute cisplatin-induced nausea and vomiting. Cancer Chemotherapy and Pharmacology 23: 389–391, 1989aPubMedCrossRefGoogle Scholar
  96. Marty M, Pouillart P, Scholl S, Droz JP, Azab M, et al. Comparison of the 5-hydroxytryptamine (serotonin) antagonist ondansetron (GR38302F) with high-dose metoclopramide in the control of cisplatin-induced emesis. New England Journal of Medicine 322: 816–821, 1990bPubMedCrossRefGoogle Scholar
  97. McRitchie B, McClelland CM, Cooper SM, Turner DH, Sanger G. Dopamine antagonists as anti-emetics and as stimulants of gastric motility. In Bennet A & Velo G (Eds) Mechanisms of gastrointestinal motility and secretion, pp. 287–301, Plenum Press, New York, 1984CrossRefGoogle Scholar
  98. Metz R, Conroy TH, Krakowski I, Orwin J, Hardenberg J. Efficacité d’un antagoniste du récepteur 5-HT3 (MDL 72.222) dans la prévention des nausées et vomissements associés à l’administration du cisplatine. Cancer Communication 2: 207–212, 1988aGoogle Scholar
  99. Metz R, Conroy TH, Krakowski I, Orwin J, Robin M. MDL 72.222 (MDL): an effective 5-HT3 antagonist to prevent cisplatin induced nausea and vomiting. Abstract. Second Conference of the Service Oncologie Médicale Pitié-Salpétrière, Paris, February, 1988bGoogle Scholar
  100. Milne RJ, Heel RC. Ondansetron: therapeutic use as an antiemetic. Drugs 41: 574–595, 1991PubMedCrossRefGoogle Scholar
  101. Miner WD, Sanger GJ. Inhibition of cisplatin induced vomiting by selective 5-hydroxytryptamine M-receptor antagonism. British Journal of Pharmacology 88: 497–499, 1986PubMedCrossRefGoogle Scholar
  102. Miner WD, Sanger GJ, Turner DH. Comparison of the effect of BRL 24924, metoclopramide and domperidone on cisplatin-induced emesis in the ferret. British Journal of Pharmacology 88: 374P, 1986CrossRefGoogle Scholar
  103. Monkovic I, Willner D, Adam MA, Brown M, Crenshaw RR, et al. Substituted benzamides. 1. Potential nondopaminergic antagonists of chemotherapy-induced nausea and emesis. Journal of Medicinal Chemistry 31: 1548–1558, 1988Google Scholar
  104. Monkovic IM, Gylys JA. Developments in the antiemetic area: chemistry, pharmacology and therapy. In Ellis GP & West GB (Eds) Progress in medicinal chemistry, Vol. 27, pp. 297-323, Elsevier Science Publishers, 1990Google Scholar
  105. Montgomery SA, Fineberg N. Is there a relationship between serotonin receptor subtypes and selectivity of response in specific psychiatric illnesses? British Journal of Psychiatry 155 (Suppl. 8): 63–70, 1986Google Scholar
  106. Orwin JM, Fozard JR. Blockade of the flare response to intradermal 5-hydroxytryptamine in man by MDL 72,222, a selective antagonist at neuronal 5-hydroxytryptamine receptors. European Journal of Clinical Pharmacology 30: 209–212, 1986PubMedCrossRefGoogle Scholar
  107. Papp M, Przegalinski E. The 5-HT3 receptor antagonists ICS 205-930 and GR38032F, putative anxiolytic drugs, differ from diazepam in their pharmacological profile. Journal of Psychopharmacology 3: 14–20, 1989PubMedCrossRefGoogle Scholar
  108. Pendergrass K, Hainsworth J, Harvey W, Kasimis B, Finn A. Ondansetron (OND): more effective than metoclopramide (MCP) in the prevention of cisplatin (DDP)-induced nausea (N) and vomiting (V). Abstract 1234. Proceedings of the American Society of Clinical Oncology 9: 319, 1990Google Scholar
  109. Pendley CE, Eff R, Gessner G, Martin GE. The potent anti-emetic agent RG 12915 binds with high affinity and selectivity to central 5-HT3 receptors. FASEB Journal 4: A475, 1990Google Scholar
  110. Perez EA, Gandara DR, Plezia PM, Neidhardt JA, O’Bryan RM, et al. Exploratory dose-finding study of zacopride in the prevention of cisplatin-induced emesis. Abstract 1306. Proceedings of the American Society of Clinical Oncology 9: 337, 1990Google Scholar
  111. Peroutka SJ, Hamik A. [3H]-Quipazine labels 5-HT3 recognition sites in rat cortical membranes. European Journal of Pharmacology 148: 297–299, 1988PubMedCrossRefGoogle Scholar
  112. Peroutka SJ, Sleight AJ, McCarthy BG, Pierce PA, Schmidt AW, et al. The clinical utility of pharmacological agents that act at serotonin receptors. Journal of Neuropsychiatry 1: 253–262, 1989Google Scholar
  113. Peroutka SJ, Snyder SH. Antiemetics: neurotransmitter receptor binding predicts therapeutic actions. Lancet 1: 658–660, 1982PubMedCrossRefGoogle Scholar
  114. Pinkerton CR, Williams NB, Mellor ST, McElwain TJ. 5HT3 antagonist ondansetron: an effective out-patient anti-emetic in cancer treatment. Archives of Disease in Childhood 65: 822–825, 1990PubMedCrossRefGoogle Scholar
  115. Plosker GL, Goa KL. Granisetron: a review of its pharmacological properties and therapeutic use as an antiemetic. Drugs 42: in press, 1991Google Scholar
  116. Postmus P, Smit E, Mitter A, Cherng N, Canetta R, et al. Randomized, double-blind, crossover placebo-controlled trial of batanopride (BMY-25801) in patients receiving non-cisplatin emetogenic chemotherapy. Abstract 1289. Proceedings of the American Society of Clinical Oncology 9: 333, 1990Google Scholar
  117. Priestman TJ. Clinical studies with ondansetron in the control of radiation-induced emesis. European Journal of Cancer and Clinical Oncology 25 (Suppl. 1): S29-S33, 1989Google Scholar
  118. Priestman TJ, Upadhyaya BK, Palmer JL, Colthup PV. Pharmacokinetics of the anti-emetic ondansetron in elderly cancer patients. Abstract W9:21. XVth ESMO Congress, Copenhagen, 1990Google Scholar
  119. Richardson BP, Engel G, Donatsch P. Identification of serotonin M-receptor subtypes and their specific blockage by a new class of drugs. Nature 31: 126–131, 1985CrossRefGoogle Scholar
  120. Roila F, Basurto C, Bracarda S, Sassi M, Lupattelli M, et al. Double-blind cross-over trial of single vs divided dose of metoclopramide in a combined regimen for treatment of cisplatin-induced emesis. European Journal of Cancer 27: 119–121, 1991aPubMedCrossRefGoogle Scholar
  121. Roila F, Tonato M, Cognetti F, Cortesi E, Fayalli G, et al. Prevention of cisplatin-induced emesis: a double-blind multicenter randomized crossover study comparing, ondansetron and ondansetron plus dexamethasone. Journal of Clinical Oncology 9: 675–678, 1991bPubMedGoogle Scholar
  122. Rusthoven J, on behalf of the National Cancer Institute of Canada Clinical Trials Qroup and Bristol-Myers Squibb. Randomized, double-blind controlled trial testing the dose-response and overall efficacy of batanopride in patients receiving moderately emetogenic chemotherapy. Abstract W9:18. XVth ESMO Congress, Copenhagen, 1990Google Scholar
  123. Sancilio LF, Pinkus LM, Jackson CB, Munson Jr HR, Emetic activity of zocopride in ferrets and its antagonism by pharmacological agents. European Journal of Pharmacology 181: 303–306,1990PubMedCrossRefGoogle Scholar
  124. Sartiano GP, Early W, Early J, Fairchild CJ, Crenshaw RR, et al. BMY-25801-01 (BMY): a non-antidopaminergic agent to prevent cisplatin-induced nausea and vomiting. Proceedings of the American Society of Clinical Oncology 6: 272, 1987Google Scholar
  125. Saynor DA, Dixon CM. The metabolism of ondansetron. European Journal of Cancer and Clinical Oncology 25 (Suppl. 1): 75-77, 1989Google Scholar
  126. Schmoll HJ. The role of ondansetron in the treatment of emesis induced by non-cisplatin-containing chemotherapy regimes. European Journal of Cancer and Clinical Oncology 25 (Suppl. 1): S35-S39, 1989Google Scholar
  127. Seinen H, Zonnenberg BA, Tjia P, Neijt JP. The effect of three dose levels of ICS205-930 (a selective 5HT-3 antagonist) on cisplatin-induced nausea and vomiting. European Journal of Cancer and Clinical Oncology 25: 1333–1335, 1989CrossRefGoogle Scholar
  128. Seynaeve C, de Mulder P, van Liessum P, Lane-Allman E, Schmitz P, et al. A positive correlation of the plasma ondansetron level with the control of cisplatin induced emesis. Abstract W9:16. XVth ESMO Congress, Copenhagen, 1990Google Scholar
  129. Sledge GW, Einhorn LH, Nagy C, Finn AL, Patrick SE. Randomized trial of ondansetron (OND) and metoclopramide (MCP) as antiemetic therapy for cisplatin-based chemotherapy. Abstract 1248. Proceedings of the American Society of Clinical Oncology 9: 323, 1990Google Scholar
  130. Smaldone L, Manghani K, Fairchild C, Aapro MS, Sartiano G, et al. Dose-range evaluation of BMY-25801, a non-dopaminergic antiemetic for cancer chemotherapy. Abstract 249. Cancer Chemotherapy and Pharmacology 23 (Suppl.), 1988Google Scholar
  131. Smith DB, Newlands ES, Rustin GJS, Howell N, Begent RHJ, et al. A double blind randomised crossover trial comparing ondansetron + dexamethasone with ondansetron + placebo as antiemetic prophylaxis against high dose cisplatin chemotherpay. Abstract 1127. Proceedings of the American Society of Clinical Oncology 10: 321, 1991Google Scholar
  132. Smith IE, on behalf of the Granisetron Study Group. A dose-finding study of granisetron in patients receiving moderately emetogenic cytostatic chemotherapy. European Journal of Cancer 26 (Suppl. 1): S19–S23, 1990PubMedGoogle Scholar
  133. Smith RN. Safety of ondansetron. European Journal of Cancer and Clinical Oncology 25 (Suppl. 1): S47-S50, 1989Google Scholar
  134. Smith WL, Alphin RS, Jackson CB, Sancilio LF. The antiemetic profile of zacopride. Journal of Pharmacy and Pharmacology 41: 101–105, 1989PubMedCrossRefGoogle Scholar
  135. Smith WW, Sancilio LF, Owera-Atepo JB, Naylor RJ, Lambert L. Zacopride, a potent 5-HT3 antagonist. Journal of Pharmacy and Pharmacology 40: 301–302, 1988PubMedCrossRefGoogle Scholar
  136. Sorbe B, Frankendal B, Glimelius B, Hansen O, Hoegberg TH, et al. A multicentre randomised study comparing the anti-emetic effects of the 5-HT3 antagonist ICS 205-930 with a metoclopramide-containing anti-emetic cocktail in patients receiving cisplatin chemotherapy. Abstract W9:17. XVth ESMO Congress, Copenhagen, 1990Google Scholar
  137. Soukop M, on behalf of the Granisetron Study Group. A comparison of two dose levels of granisetron in patients receiving high-dose cisplatin. European Journal of Cancer 26 (Suppl. 1): S15–S19, 1990PubMedGoogle Scholar
  138. Stamatakis L, Michel J, Van Belle S, Cocquyt V, Keppens C, et al. ICS 205-930: a dose finding study in the prevention of cisplatin induced nausea and vomiting. Proceedings of the American Society of Clinical Oncology 8: 327, 1989Google Scholar
  139. Sun JH, Imondi AR. ADR-847 and ADR-851: unique anti-emetics for cancer chemotherapy-induced emesis. FASEB Journal A1053, 1988Google Scholar
  140. Tabona MV. An overview on the use of granisetron in the treatment of emesis associated with cytostatic chemotherapy. European Journal of Cancer 26 (Suppl. 1): S37-S41, 1990Google Scholar
  141. Thomas DR, Nelson DR, Blackburn TP, Wood MD. BRL 46470: a novel 5-HT3 receptor antagonist. Abstract presented at the summer meeting, British Association for Psychopharmacology, 1990Google Scholar
  142. Tyers MB, Bunce XT, Humphrey PPA. Pharmacological and antiemetic properties of ondansetron. European Journal of Cancer and Clinical Oncology 25 (Suppl. 1): S15–S19, 1989Google Scholar
  143. Tyson LB, Gralla RJ, Kris MG, Clark RA. Phase I antiemetic study of the serotonin antagonist ICS 205-930. Abstract 1287. Proceedings of the American Society of Clinical Oncology 8: 330, 1989Google Scholar
  144. Tyson LB, Kris MG, Baltzer L, Clark RA, Rigas JR. Combining ondansetron with dexamethasone: a randomised antiemetic trial comparing two ondansetron schedules in patients receiving cisplatin. Abstract 1208. Proceedings of the American Society of Clinical Oncology 10: 341, 1991Google Scholar
  145. Upward JW, Arnold BDC, Link C, Pierce DM, Allen A, et al. The clinical pharmacology of granisetron (BRL 43694), a novel specific 5-HT3 antagonist. European Journal of Cancer 26 (Suppl. 1): S12-S15, 1990Google Scholar
  146. Venner P, for the Clinical Trials Group of the National Cancer Institute of Canada. Granisetron for high dose cisplatin (HDCP) induced emesis: a randomized double-blind study. Abstract 1238. Proceedings of the American Society of Clinical Oncology 9: 320, 1990Google Scholar
  147. Villalon CM, Den Boer MO, Heiligers JPL, Saxena PR. Mediation of 5-hydroxytryptamine-induced tachycardia in the pig by the putative 5-HT4 receptor. British Journal of Pharmacology 100: 665–667, 1990aPubMedCrossRefGoogle Scholar
  148. Villalon CM, Heiligers J, Den Boer MO, Saxena PR. Putative 5-HT4 receptor mediates 5-hydroxytryptamine-induced tachycardia in the anaesthetized pig. European Journal of Pharmacology 183: 1160, 1990bCrossRefGoogle Scholar
  149. Waeber C, Dixon K, Hoyer D, Palacios JM. Localisation by auto-radiography of neuronal 5-HT-3 receptors in the mouse CNS. European Journal of Pharmacology 151: 351–352, 1988PubMedCrossRefGoogle Scholar
  150. Waeber C, Hoyer D, Palacios JM. 5-Hydroxytryptamine3 receptors in the human brain: autoradiographic visualization using [3H]ICS 205-930. Neuroscience 31: 393–400, 1989PubMedCrossRefGoogle Scholar
  151. Warr D. A double-blind randomized comparison of the novel antiemetic BRL43694A versus dexamethasone plus prochlor-perazine. Abstract P-0515. Proceedings of the European Congress of Clinical Oncology 5, 1989Google Scholar
  152. Watling KJ, Aspley S, Swain CJ, Saunders J. [3H]-Quaternised ICS 205-930 labels 5-HT3 receptor binding sites in rat brain. European Journal of Pharmacology 149: 397–398, 1988PubMedCrossRefGoogle Scholar
  153. Williams P. An open trial of ondansetron (GR38032F) in the treatment of acute schizophrenia. Abstract B.54. Schizophrenia Research 3: 48, 1990CrossRefGoogle Scholar
  154. Wong DT, Robertson DW, Reid LR. Specific [3H]LY278584 binding to 5-HT3 recognition sites in rat cerebral cortex. European Journal of Pharmacology 166: 107–110, 1989PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 1991

Authors and Affiliations

  • Matti S. Aapro
    • 1
    • 2
  1. 1.Division d’Onco-HématologieHôpital Cantonal UniversitaireGenève 4Switzerland
  2. 2.Centre AnticancéreuxGenolierSwitzerland

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