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Drugs

, Volume 52, Issue 5, pp 773–794 | Cite as

Ondansetron

A Review of its Pharmacology and Preliminary Clinical Findings in Novel Applications
  • Michelle I. Wilde
  • Anthony Markham
Drug Evaluation

Abstract

Synopsis

The use of ondansetron, a selective serotonin 5-HT3 receptor antagonist, is well established in patients with nausea and vomiting associated with cancer chemotherapy, radiotherapy or anaesthesia and surgery. The wide distribution of 5-HT3 receptors in the body and the role of these receptors in disease have provided the rationale for investigation of ondansetron in novel applications.

Preliminary data have shown ondansetron to have clinical benefit in patients with nausea and vomiting associated with drug overdosage or poisoning, anti-infective or antidepressant therapies, uraemia or neurological trauma, and in patients with pruritus. Patients with gastrointestinal motility disorders (e. g. carcinoid syndrome, irritable bowel syndrome, diarrhoea associated with cryptosporidiosis or diabetes, and chronic refractory diarrhoea) have also shown some improvement when treated with ondansetron, as have patients with certain pain or CNS-related disorders [e. g. alcohol (ethanol) dependence, opiate withdrawal, vertigo, cerebellar tremor and Parkinson’s disease treatment-related psychosis].

In contrast to conventional antiemetics, ondansetron is generally well tolerated with a lower incidence of sedation and only isolated case reports of extrapyramidal reactions. Furthermore, unlike dopamine receptor-blocking neuroleptics, ondansetron does not appear to worsen the symptoms of Parkinson’s disease.

Thus, in addition to its established indications, preliminary results suggest that ondansetron may be beneficial in a number of novel applications. This drug may represent a treatment alternative in patients with refractory disease, or an effective treatment of conditions for which current therapies are either poorly tolerated or not available. Further investigation of ondansetron in a range of potential new applications appears to be warranted.

Pharmacodynamic Properties

Ondansetron, a carbazole derivative, is a competitive and selective antagonist of serotonin 5-HT3 receptors. 5-HT3 receptors are present in both the central and peripheral nervous systems and are associated with several serotonin-mediated physiological and pathological processes.

The mechanisms by which ondansetron produces its clinical effects in the novel applications reviewed are not fully understood. Effects related to the peripheral nervous system are thought to involve inhibition of 5-HT3 receptor-induced depolarisation of vagal afferent nerves and inhibition of myenteric neurons and 5-HT3 receptor-mediated nociceptive responses. Blockade of 5-HT3 receptors at central sites (including the area postrema, nucleus tractus solitarius, amygdala and dorsal raphe nucleus) and blockade of dopamine release/cell firing in the nucleus accumbens (via 5-HT3 receptor antagonism) are possible mechanisms of CNS-related effects of ondansetron.

In animal studies, ondansetron has been shown to delay or increase gastric emptying, increase gastric mucosal blood flow and basal acid and sodium secretion, prevent or reduce stress- or alcohol (ethanol)-induced gastric mucosal damage, inhibit fluid loss and inflammation in small bowel obstruction, and reduce abdominal responses to rectal distension and viscerosensitive changes during experimental colitis. In healthy volunteers, ondansetron did not significantly affect gastric emptying, distension or compliance. However, colonic transit times were significantly longer with ondansetron than with placebo, and ondansetron inhibited tonic colonic postprandial responses. Duodenal motility, small intestinal transit and mouth to caecum transit times were unaffected.

The drug had no significant effects on basal cognitive performance and/or scopolamine-induced cognitive and/or behavioural effects in elderly or young healthy volunteers. However, ondansetron has been shown to have favourable effects on cognitive performance in animal studies.

In general, alcohol (ethanol) consumption was either reduced or unaffected by ondansetron in animal models of alcohol dependence. Ondansetron had no significant effects on self-administration of cocaine, heroin or nicotine, or on nicotine hypersensitivity in animals. However, ondansetron reduced withdrawal symptoms and had varied effects on behaviour associated with chronic alcohol, cocaine, benzodiazepine or nicotine administration in animals. Pretreatment with intravenous ondansetron did not modify the effects of alcohol in 2 studies of social drinkers. However, oral ondansetron significantly attenuated the pleasurable effects of alcohol in social drinkers and decreased their desire to drink.

Ondansetron inhibited or reduced raised mesolimbic dopamine activity and antagonised increased locomotor activity caused by dopamine excess in animals; dopamine metabolism was unaffected. Ondansetron has shown variable anxiolytic activity in animal models of anxiety. Data on the effects of ondansetron on the development of tolerance to or withdrawal from benzodiazepines in animals are varied. Ondansetron did not impair psychomotor and/or driving performance in healthy volunteers or patients with anxiety.

Pharmacokinetic Properties

In healthy adults, oral ondansetron (8mg in single or multiple doses) is completely and rapidly absorbed with a mean maximum plasma concentration (Cmax) of 20 to 48 μg/L, area under the plasma concentration-time curve of 101 to 351 μg/L • h and time to Cmax of 1 to 2.1 hours. Bioavailability is only approximately 60% as a result of significant first-pass metabolism. There is no evidence of accumulation after repeated oral doses, and coadministration with food or antacids does not appear to affect absorption. Oral ondansetron has a terminal elimination half-life of ≈ 2.5 to 5.4 hours.

Oral ondansetron has a volume of distribution of approximately 135 to 160L and binds only moderately to plasma proteins (70 to 76%). CSF concentrations are < 15% of plasma concentrations.

Ondansetron undergoes extensive hepatic oxidative metabolism. Metabolites contribute little to the activity of the drug and are excreted in the urine and faeces; renal clearance accounts for less than 5% of total unaltered ondansetron clearance.

Cytochromes P450 IA2, 2D6 and 3A are involved in the hydroxylation of ondansetron; therefore, drug interactions between ondansetron and agents that compete for these enzymes could potentially occur. However, no significant pharmacokinetic differences for ondansetron were observed in poor or extensive debrisoquine metabolisers.

The overall pharmacokinetics of ondansetron in children appear to be similar to those in adults. Ondansetron clearance is reduced in patients with hepatic impairment; dosage adjustments may be necessary, especially in patients with severe hepatic impairment (see Dosage and Administration summary).

Clinical Findings in Novel Applications

The wide distribution of 5-HT3 receptors throughout the body, the ability of ondansetron to act at multiple sites and the promising findings from animal studies and studies in healthy volunteers have provided the rationale for investigation of this drug in several novel applications. However, much of the available data on ondansetron in these applications is of a preliminary nature. Reports to date have involved only a small number of patients, most with refractory disease, and current treatments for many of the applications reviewed are minimally effective, poorly tolerated or nonexistent.

Single or multiple doses of intravenous ondansetron 5 to 10mg (or 0.14 or 0.15 mg/kg) or oral ondansetron 8mg relieved or improved nausea and/or vomiting associated with the following: theophylline, paracetamol (acetaminophen), colchicine or baclofen overdosage or poisoning and/or their antidotes/treatments; anti-infective and antidepressant therapies; uraemia; and neurological trauma.

Some clinical improvement in gastrointestinal symptoms with oral or intravenous ondansetron 8 to 16mg 2 or 3 times daily has been observed in patients with carcinoid syndrome or other gastrointestinal motility disorders including diarrhoea associated with cryptosporidiosis or diabetes and chronic refractory diarrhoea. Data from 2 placebo-controlled studies in patients with irritable bowel syndrome indicate that ondansetron significantly improved stool consistency (and stool frequency in 1 study); however, there were no between-treatment differences for a number of other clinical parameters in these studies. No beneficial effect was seen in patients with gastric stasis syndrome or diabetic gastroparesis.

Single or multiple doses of intravenous and/or oral ondansetron 4 or 8mg relieved or reduced pruritus in patients with cholestatic disease, terminal uraemia or itching following intrathecal morphine administration. This effect was significant compared with placebo in a small number of patients with cholestatic disease.

Various doses/dosages of ondansetron have also shown clinical benefit in some pain or CNS-related disorders (including nonsevere alcohol dependence, opiate withdrawal, intractable vertigo, cerebellar tremor and Parkinson’s disease treatment-related psychosis). Anxiety was not reduced by this agent in the one available study to date.

Tolerability and Drug Interactions

Tolerability data on ondansetron in potential new applications are limited. According to available clinical reports, headache and constipation were the adverse events most commonly observed in patients with nausea and vomiting associated with anti-infective therapy or in patients with cerebellar tremor, vertigo or Parkinson’s disease treatment-related psychosis.

These findings are supported by tolerability data from postoperative nausea and vomiting trials involving a total of 1900 patients. Headache (14%), dizziness (12%) and drowsiness/sedation (2%) were the most commonly reported adverse effects; their incidence was similar with ondansetron and placebo.

In contrast to conventional antiemetics, ondansetron has been associated with a lower incidence of sedation and only isolated case reports of extrapyramidal reactions. There have been reports (>20 cases to date) of anaphylactoid/ anaphylactic reactions associated with intravenous ondansetron.

Abnormalities in liver function tests have been associated with ondansetron therapy. No adverse cardiovascular events have been reported.

Dosage and Administration

Specific dosage recommendations for the use of ondansetron in potential new applications are not available at present. Oral and intravenous dosages of ondansetron have ranged widely in the available literature. In patients with severe hepatic impairment, the dosage of ondansetron should be ≤8mg once daily. Dosage adjustments do not appear to be required in the elderly, in patients with renal impairment or on the basis of gender alone.

Keywords

Irritable Bowel Syndrome Ondansetron Granisetron Carcinoid Syndrome Hyperemesis Gravidarum 
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. 1.
    Kim H, Rosenberg SA, Steinberg SM, et al. A randomized double-blinded comparison of the antiemetic efficacy of ondansetron and droperidol in patients receiving high-dose interleukin-2. J Immunother Emphasis Tumor Immunol 1994 Jul; 16: 60–5PubMedCrossRefGoogle Scholar
  2. 2.
    Naguib M, Bakry AK, Khoshim MHB, et al. Prophylactic anti-emetic therapy with ondansetron, tropisetron, granisetron and metoclopramide in patients undergoing laparoscopic cholecystectomy: a randomized, double-blind comparison with placebo. Can J Anaesth 1996 Mar; 43: 226–31PubMedCrossRefGoogle Scholar
  3. 3.
    Markham A, Sorkin EM. Ondansetron: an update of its therapeutic use in chemotherapy-induced and postoperative nausea and vomiting. Drugs 1993 Jun; 45: 931–52PubMedCrossRefGoogle Scholar
  4. 4.
    Paxton LD, McKay AC, Mirakhur RK. Prevention of nausea and vomiting after day case gynaecological laparoscopy: a comparison of ondansetron, droperidol, metoclopramide and placebo. Anaesthesia 1995 May; 50: 403–6PubMedCrossRefGoogle Scholar
  5. 5.
    Joslyn AF. Ondansetron, clinical development for postoperative nausea and vomiting: current studies and future directions. Anaesthesia 1994 Jan; 49 Suppl.: 34–7PubMedCrossRefGoogle Scholar
  6. 6.
    Peroutka SJ. Serotonin and neuropsychiatrie disorders: implications for the discovery of new psychotherapeutic agents. VI. Serotonin receptor subtypes and neuropsychiatric diseases: focus on 5-HT1D and 5-HT3 receptor agents. Pharmacol Rev 1991 Dec; 43: 579–86PubMedGoogle Scholar
  7. 7.
    Gyermek L. 5-HT3 receptors: pharmacologic and therapeutic aspects. J Clin Pharmacol 1995 Sep; 35: 845–55PubMedGoogle Scholar
  8. 8.
    Oxford AW, Bell JA, Kilpatrick GJ, et al. Ondansetron and related 5-HT3 antagonists: recent advances. Prog Med Chem 1992; 29: 239–70PubMedCrossRefGoogle Scholar
  9. 9.
    Grant KA. The role of 5-HT3 receptors in drug dependence. Drug Alcohol Depend 1995; 38: 155–71PubMedCrossRefGoogle Scholar
  10. 10.
    Allan SG. The 5HT3 antagonists. New generation antiemetics. Curr Ther 1993 Jul; 34: 15–8Google Scholar
  11. 11.
    Tyers MB. Pharmacology and preclinical antiemetic properties of ondansetron. Semin Oncol 1992 Aug; 19 Suppl. 10: 1–8PubMedGoogle Scholar
  12. 12.
    Naylor RJ, Rudd JA. Pharmacology of ondansetron. Eur J Anaesthesiol 1992 Nov; 9 Suppl. 6: 3–10Google Scholar
  13. 13.
    Gebauer A, Merger M, Kilbinger H. Modulation by 5-HT3 and 5-HT4 receptors of the release of 5-hydroxytryptamine from the guinea-pig small intestine. Naunyn Schmiedebergs Arch Pharmacol 1993; 347: 137–40PubMedCrossRefGoogle Scholar
  14. 14.
    Costall B, Naylor RJ. Serotonin and psychiatric disorders. A key to new therapeutic approaches. Arzneimittel Forschung 1992 Feb; 42: 246–9PubMedGoogle Scholar
  15. 15.
    Deegan R. Ondansetron: pharmacology of a specific 5HT3-receptor antagonist. Am J Med Sci 1992 Dec; 304: 373–8PubMedCrossRefGoogle Scholar
  16. 16.
    Cho CH, Koo MWL, Ko JKS. Modulatory role of 5-HT3 receptors in gastric function and ethanol- induced mucosal damage in rat stomachs. Pharmacology 1994 Sep; 49: 137–43PubMedCrossRefGoogle Scholar
  17. 17.
    Kaneko H, Mitsuma T, Morise K, et al. Effect of serotonin on the immunoreactive thyrotropin-releasing hormone concentrations of the rat stomach. Digestion 1992; 53: 149–56PubMedCrossRefGoogle Scholar
  18. 18.
    Endo T, Minami M, Monma Y, et al. Effect of ondansetron, a 5-HT3 antagonist, on copper sulfate-induced emesis in the ferret. Biog Amines 1991; 8(2): 79–86Google Scholar
  19. 19.
    Malinowska B, Gothert M, Godlewski G, et al. Inhibitory effect of ethanol on the 5-hydroxytryptamine-induced Bezold-Ja-risch reflex-involvement of peripheral 5-HT3 receptors. Eur J Pharmacol 1995 May 26; 293: 71–6PubMedCrossRefGoogle Scholar
  20. 20.
    Martelletti P, Stirparo G, Rinaldi C, et al. Upregulated expression of peripheral serotonergic receptors in migraine and cluster headache by sumatriptan. Int J Clin Pharmacol Res 1994; 14(5–6): 165–75PubMedGoogle Scholar
  21. 21.
    Yoshioka M, Ikeda T, Abe M, et al. Effect of 5-hydroxytryptamine on external carotid nerve activity and its blockade by GR38032F in anesthetized rats. Res Commun Chem Pathol Pharmacol 1991 Oct; 74: 39–45PubMedGoogle Scholar
  22. 22.
    Hagan RM, Kilpatrick GJ, Tyers MB. Interactions between 5-HT3 receptors and cerebral dopamine function: implications for the treatment of schizophrenia and psychoactive substance abuse. Psychopharmacology 1993; 112 Suppl.: 68–75CrossRefGoogle Scholar
  23. 23.
    Montgomery AMJ, Rose IC, Herberg LJ. The effect of a 5-HT3 receptor antagonist, ondansetron, on brain stimulation reward, and its interaction with direct and indirect stimulants of central dopaminergic transmission. J Neural Transm Gen Sect 1993; 91(1): 1–11PubMedCrossRefGoogle Scholar
  24. 24.
    Fox AJ, Morton IKM. An examination of the 5-HT3 receptor mediating contraction and evoked [3H]-acetylcholine release in the guinea-pig ileum. Br J Pharmacol 1990 Nov; 101: 553–6PubMedCrossRefGoogle Scholar
  25. 25.
    Matsumoto M, Yoshioka M, Togashi H, et al. Modulation of norepinephrine release by serotonergic receptors in the rat hippocampus as measured by in vivo microdialysis. J Pharmacol Exp Ther 1995 Mar; 272: 1044–51PubMedGoogle Scholar
  26. 26.
    Mongeau R, De Montigny C, Blier P. Activation of 5-HT3 receptors enhances the electrically evoked release of [3H]nor-adrenaline in rat brain limbic structures. Eur J Pharmacol 1994 May 2; 256: 269–79PubMedCrossRefGoogle Scholar
  27. 27.
    Broocks A, Pigott T, Canter S, et al. The highly-selective 5-HT3-antagonist, ondansetron, inhibits GH secretion in healthy volunteers and patients with obsessive-compulsive disorder [abstract]. Neuropsychopharmacology 1994 May; 10 Suppl. Pt 2: 151Google Scholar
  28. 28.
    Levy AD, Li Q, Rittenhouse PA, et al. Investigation of the role of 5-HT3 receptors in the secretion of prolactin, ACTH and renin. Neuroendocrinology 1993 Jul; 58: 65–70PubMedCrossRefGoogle Scholar
  29. 29.
    Jorgensen H, Knigge U, Warberg J. Effect of serotonin 5-HT1, 5-HT2, and 5-HT3 receptor antagonists on the prolactin response to restraint and ether stress. Neuroendocrinology 1992 Sep; 56: 371–7PubMedCrossRefGoogle Scholar
  30. 30.
    Ulrich U, Nowara I, Rossmanith WG. Serotoninergic control of gonadotrophin and prolactin secretion in women. Clin En-docrinol Oxf 1994 Dec; 41: 779–85CrossRefGoogle Scholar
  31. 31.
    Costall B. The breadth of action of the 5-HT3 receptor antagonists. Int Clin Psychopharmacol 1993 Nov; 8 Suppl. 2: 3–9PubMedCrossRefGoogle Scholar
  32. 32.
    Ito H, Akuzawa S, Tsutsumi R, et al. Comparative study of the affinities of the 5-HT3 receptor antagonists, YM060 YM114 (KAE-393), granisetron and ondansetron in rat vagus nerve and cerebral cortex. Neuropharmacology 1995 Jun; 34: 631–7PubMedCrossRefGoogle Scholar
  33. 33.
    Koch KL, Xu L, Bingaman S, et al. Effects of ondansetron on morphine-induced nausea, vasopressin and gastric myoelectrical activity in healthy humans [abstract]. Gastroenterology 1993 Apr; 104 Suppl.: A535Google Scholar
  34. 34.
    Dyr W, Kostowski W. Evidence that the amygdala is involved in the inhibitory effects of 5-HT3 receptor antagonists on alcohol drinking in rats. Alcohol 1995 Jul–Aug; 12: 387–91PubMedCrossRefGoogle Scholar
  35. 35.
    Costall B, Jones BJ, Kelly ME, et al. Sites of action of ondansetron to inhibit withdrawal from drugs of abuse. Pharmacol Biochem Behav 1990 May; 36: 97–104PubMedCrossRefGoogle Scholar
  36. 36.
    Forster ER, Dockray GJ. The effect of ondansetron on gastric emptying in the conscious rat. Eur J Pharmacol 1990 Nov 27; 191: 235–8PubMedCrossRefGoogle Scholar
  37. 37.
    Costall B, Gunning SJ, Naylor RJ, et al. The effect of GR38032F, novel 5-HT3-receptor antagonist on gastric emptying in the guinea-pig. Br J Pharmacol 1987; 91: 263–4PubMedCrossRefGoogle Scholar
  38. 38.
    Ogle CW, Hui S-CG, Qiu BS, et al. 5-Hydroxytryptamine3-re-ceptor blockade protects against gastric mucosal damage in rats. Acta Physiol Hung 1992; 80: 181–8PubMedGoogle Scholar
  39. 39.
    Qiu BS, Hui S-CG, Wong D, et al. A study on the influence of peripheral or central administration of ondansetron on stress-induced gastric ulceration [abstract]. Can J Physiol Pharmacol 1994; 72 Suppl. 1: 240Google Scholar
  40. 40.
    Ogle CW, Hui S-CG. The influence of peripheral or central administration of ondansetron on stress-induced gastric ulceration in rats. Experientia 1995 Aug 16; 51: 786–9PubMedCrossRefGoogle Scholar
  41. 41.
    Morteau O, Julia V, Eeckhout C, et al. Influence of 5-HT3 receptor antagonists in visceromotor and nociceptive responses to rectal distension before and during experimental colitis in rats. Fundam Clin Pharmacol 1994; 8: 553–62PubMedCrossRefGoogle Scholar
  42. 42.
    Moss HE, Sanger GJ. The effects of granisetron, ICS 205-930 and ondansetron on the visceral pain reflex induced by duodenal distension. Br J Pharmacol 1990 Jul; 100: 497–501PubMedCrossRefGoogle Scholar
  43. 43.
    Nellgård P, Jönsson A, Cassuto J. Anti-inflammatory and antisecretory effects of the 5-HT3 receptor antagonist ondansetron on intestinal obstruction in the rat [abstract]. Acta Physiol Scand 1992; 146 Suppl. 608: 61Google Scholar
  44. 44.
    Sommers DK, Van WM, Snyman JR, et al. Influence of granisetron, ondansetron and metoclopramide on gastric emptying, oro-caecal transit time and theophylline absorption from a sustained-release formulation. Med Sci Res 1994 May 1–31; 22: 329–31Google Scholar
  45. 45.
    Van Wyk M, Sommers D-K, Snyman JR, et al. The effect of metoclopramide, ondansetron, and granisetron on liquid gastric emptying in normal subjects. Curr Ther Res 1995; 56(6): 581–6CrossRefGoogle Scholar
  46. 46.
    Gore S, Gilmore IT, Haigh CG, et al. Colonic transit in man is slowed by ondansetron (GR38032F), a selective 5-hydroxy-tryptamine receptor (type 3) antagonist. Aliment Pharmacol Ther 1990 Apr; 4: 139–44PubMedCrossRefGoogle Scholar
  47. 47.
    Wilmer A, Tack J, Coremans G, et al. Effect of ondansetron, a 5-HT3-receptor antagonist, on perception of gastric distension and gastric compliance in healthy man [abstract]. Gastroenterology 1993 Apr; 104 Suppl.: A603Google Scholar
  48. 48.
    Fiorucci S, Santucci L, Morelli A. 5-Hydroxytryptamine 3-re-ceptor antagonist modulates gallbladder emptying and motilin release induced by erythromycin. Dig Dis Sci 1993 Dec; 38: 2236–40PubMedCrossRefGoogle Scholar
  49. 49.
    Talley NJ, Phillips SF, Haddad A, et al. GR 38032F (ondansetron), a selective 5HT3 receptor antagonist, slows colonic transit in healthy man. Dig Dis Sci 1990 Apr; 35: 477–80PubMedCrossRefGoogle Scholar
  50. 50.
    von der Ohe MR, Hanson RB, Camilleri M. Serotonergic mediation of postprandial colonic tonic and phasic responses in humans. Gut 1994 Apr; 35: 536–41PubMedCrossRefGoogle Scholar
  51. 51.
    Scolapio JS, Camilleri M, von der Ohe MR, et al. Ascending colon response to feeding: evidence for a 5-hydroxytryptamine-3 mechanism. Scand J Gastroenterol 1995 Jun; 30: 562–7PubMedCrossRefGoogle Scholar
  52. 52.
    Talley NJ, Phillips SF, Haddad A, et al. Effect of selective 5HT3 antagonist (GR 38032F) on small intestinal transit release of gastrointestinal peptides. Dig Dis Sci 1989 Oct; 34: 1511–5PubMedCrossRefGoogle Scholar
  53. 53.
    Wilmer A, Coremans G, Janssens J, et al. Effects of ondansetron, a selective 5-HT3 receptor antagonist, on duodenal motility in man [abstract]. Gastroenterology 1992 Apr; 102 (Pt 2): A534Google Scholar
  54. 54.
    Brown NJ, Horton A, Rumsey RDE, et al. The influence of ondansetron & granisetron on the gastrointestinal response to ileal lipid infusion [abstract]. J Gastrointest Motil 1992 Sep; 4: 212Google Scholar
  55. 55.
    Allescher HD, Willis S, Stoschus B, et al. Effect of molsidomin and ondansetron on human esophageal motility [abstract]. J Gastrointest Motil 1993 Sep; 5: 178Google Scholar
  56. 56.
    Barnes JM, Costall B, Coughlan J, et al. The effects of ondansetron, a 5-HT3 receptor antagonist, on cognition in rodents and primates. Pharmacol Biochem Behav 1990 Apr; 35: 955–62PubMedCrossRefGoogle Scholar
  57. 57.
    Carey GJ, Costall B, Domeney AM, et al. Ondansetron and arecoline prevent scopolamine-induced cognitive deficits in the marmoset. Pharmacol Biochem Behav 1992 May; 42: 75–83PubMedCrossRefGoogle Scholar
  58. 58.
    Domeney AM, Costall B, Gerrard PA, et al. The effect of ondansetron on cognitive performance in the marmoset. Pharmacol Biochem Behav 1991 Jan; 38: 169–75PubMedCrossRefGoogle Scholar
  59. 59.
    Fontana DJ, Daniels SE, Henderson C, et al. Ondansetron improves cognitive performance in the Morris water maze spatial navigation task. Psychopharmacology 1995 Aug; 120(4): 409–17PubMedCrossRefGoogle Scholar
  60. 60.
    Hodges H, Sowinski P, Turner JJ, et al. Comparison of the effects of the 5-HT3 receptor antagonists WAY-100579 and ondansetron on spatial learning in the water maze in rats with excitotoxic lesions of the forebrain cholinergic projection system. Psychopharmacology 1996; 125: 146–61PubMedCrossRefGoogle Scholar
  61. 61.
    Little JT, Broocks A, Martin A, et al. Serotonergic modulation of anticholinergic effects on cognition and behavior in elderly humans. Psychopharmacology 1995 Aug; 120(3): 280–8PubMedCrossRefGoogle Scholar
  62. 62.
    Broocks A, Little JT, Martin A, et al. The effect of ondansetron and m-CPP on scopolamine-induced cognitive and behavioral changes in young healthy volunteers [abstract]. Pharmacopsychiatry 1995 Sep; 28: 168Google Scholar
  63. 63.
    Meert TF. Effects of various serotonergic agents on alcohol intake and alcohol preference in Wistar rats selected at two different levels of alcohol preference. Alcohol Alcohol 1993 Mar; 28: 157–70PubMedGoogle Scholar
  64. 64.
    Tomkins DM, Le AD, Sellers EM. Effect of the 5-HT3 antagonist ondansetron on voluntary ethanol intake in rats and mice maintained on a limited access procedure. Psychopharmacology 1995 Feb; 117(4): 479–85PubMedCrossRefGoogle Scholar
  65. 65.
    Beardsley PM, Lopez OT, Gullikson G, et al. Serotonin 5-HT3 antagonists fail to affect ethanol self-administration of rats. Alcohol 1994 Sep–Oct; 11: 389–95PubMedCrossRefGoogle Scholar
  66. 66.
    Kostowski W, Bisaga A, Jankowska E, et al. Studies on the effects of certain 5-HT-3 receptor antagonists on ethanol preference and withdrawal seizures in the rat. Pol J Pharmacol 1994 May–Jun; 46: 133–7PubMedGoogle Scholar
  67. 67.
    Higgins GA, Tomkins DM, Fletcher PJ, et al. Effect of drugs influencing 5-HT function on ethanol drinking and feeding behaviour in rats: studies using a drinkometer system. Neurosci Biobehav Rev 1992; 16: 535–52PubMedCrossRefGoogle Scholar
  68. 68.
    Svensson L, Fahlke C, Hard E, et al. Involvement of the serotonergic system in ethanol intake in the rat. Alcohol 1993; 10: 219–24PubMedCrossRefGoogle Scholar
  69. 69.
    Costall B, Jones BJ, Kelly ME, et al. Ondansetron inhibits a behavioural consequence of withdrawing from drugs of abuse. Pharmacol Biochem Behav 1990 Jun; 36: 339–44PubMedCrossRefGoogle Scholar
  70. 70.
    Vanhaaren F. Effects of cocaine alone and in combination with prazosin or ondansetron on multiple fixed-interval fixed-ratio performance in pigeons. Pharmacol Biochem Behav 1992 Aug; 42: 849–53CrossRefGoogle Scholar
  71. 71.
    King GR, Joyner CM, Ellinwood Jr EH. 5-HT3 receptor modulation of behavior during withdrawal from continuous or intermittent cocaine. Pharmacol Biochem Behav 1994 Mar; 47: 399–407PubMedCrossRefGoogle Scholar
  72. 72.
    Depoortere RY, Li DH, Lane JD, et al. Parameters of self-administration of cocaine in rats under a progressive-ratio schedule. Pharmacol Biochem Behav 1993 Jul; 45: 539–48PubMedCrossRefGoogle Scholar
  73. 73.
    Peltier R, Schenk S. GR38032F, a serotonin 5-HT3 antagonist, fails to alter cocaine self-administration in rats. Pharmacol Biochem Behav 1991 May; 39: 133–6PubMedCrossRefGoogle Scholar
  74. 74.
    Higgins GA, Wang Y, Corrigall WA, et al. Influence of 5-HT3 receptor antagonists and the indirect 5-HT agonist, dexfenfluramine, on heroin self-administration in rats. Psychopharmacology Berl 1994 May; 114: 611–9PubMedCrossRefGoogle Scholar
  75. 75.
    Lane JD, Pickering CL, Hooper ML, et al. Failure of ondansetron to block the discriminative or reinforcing stimulus effects of cocaine in the rat. Drug Alcohol Depend 1992 Jun; 30: 151–62PubMedCrossRefGoogle Scholar
  76. 76.
    Joharchi N, Sellers EM, Higgins GA. Effect of 5-HT3 receptor antagonists on the discriminative stimulus properties of morphine in rats. Psychopharmacology 1993 Aug; 112: 111–5PubMedCrossRefGoogle Scholar
  77. 77.
    Arnold B, Allison K, Ivanova S, et al. 5HT3 receptor antagonists do not block nicotine induced hyperactivity in rats. Psychopharmacology 1995 May; 119: 213–21PubMedCrossRefGoogle Scholar
  78. 78.
    Doty P, Zacny JP, de Wit H. Effects of ondansetron pretreatment on acute responses to ethanol in social drinkers. Behav Pharmacol 1994 Aug; 5: 461–9PubMedCrossRefGoogle Scholar
  79. 79.
    Johnson BA, Campling GM, Griffiths P, et al. Attenuation of some alcohol-induced mood changes and the desire to drink by 5-HT3 receptor blockade: a preliminary study in healthy male volunteers. Psychopharmacology 1993 Aug; 112: 142–4PubMedCrossRefGoogle Scholar
  80. 80.
    Pei Q, Zetterström T, Leslie RA, et al. 5-HT3 receptor antagonists inhibit morphine-induced stimulation of mesolimbic dopamine release and function in the rat. Eur J Pharmacol 1993 Jan 5; 230: 63–8PubMedCrossRefGoogle Scholar
  81. 81.
    Bell JM, Tyers MB. Preclinical evaluation of the antipsychotic potential of ondansetron, a novel antagonist at the 5HT3 receptor [abstract]. J Clin Pharmacol 1991 Mar; 31: 268Google Scholar
  82. 82.
    Warburton EC, Joseph MH, Feldon J, et al. Antagonism of amphetamine-induced disruption of latent inhibition in rats by haloperidol and ondansetron: implications for a possible antipsychotic action of ondansetron. Psychopharmacology 1994 May; 114: 657–64PubMedCrossRefGoogle Scholar
  83. 83.
    Koulu M, Sjöholm B, Lappalainen J, et al. Effects of acute GR38032F (odansetron), a 5-HT3 receptor antagonist, on dopamine and serotonin metabolism in mesolimbic and nigrostriatal dopaminergic neurons. Eur J Pharmacol 1989 Oct 10; 169: 321–4PubMedCrossRefGoogle Scholar
  84. 84.
    Koulu M, Lappalainen J, Hietala J, et al. Effects of chronic administration of ondansetron (GR38032F), a selective 5-HT3 receptor antagonist, on monoamine metabolism in mesolimbic and nigrostriatal dopaminergic neurons and on striatal D2-receptor binding. Psychopharmacology 1990; 101(2): 168–71PubMedCrossRefGoogle Scholar
  85. 85.
    Silverstone PH, Oldman D, Johnson B, et al. Ondansetron, a 5-HT3 receptor antagonist, partially attenuates the effects of amphetamine: a pilot study in healthy volunteers. Int Clin Psychopharmacol 1992; 7(1): 37–43PubMedCrossRefGoogle Scholar
  86. 86.
    Handley SL, McBlane JW. 5HT drugs in animal models of anxiety. Psychopharmacology 1993 Aug; 112: 13–20PubMedCrossRefGoogle Scholar
  87. 87.
    Rodgers RJ, Cole JC, Tredwell JM. Profile of action of 5-HT3 receptor antagonists, ondansetron and WAY 100289, in the elevated plus-maze test of anxiety of mice. Psychopharmacology 1995 Feb; 117(3): 306–12PubMedCrossRefGoogle Scholar
  88. 88.
    Stefanski R, Palejko W, Kostowski W, et al. The comparison of benzodiazepine derivatives and serotonergic agonists and antagonists in 2 animal models of anxiety. Neuropharmacology 1992 Dec; 31: 1251–8PubMedCrossRefGoogle Scholar
  89. 89.
    Stefanski R, Palejko W, Bidzinski A, et al. Serotonergic innervation of the hippocampus and nucleus accumbens septi and the anxiolytic-like action of the 5-HT3 receptor antagonists. Neuropharmacology 1993 Oct; 32: 987–93PubMedCrossRefGoogle Scholar
  90. 90.
    Nevins ME, Anthony EW. Antagonists at the serotonin-3 receptor can reduce the fear-potentiated startle response in the rat: evidence for different types of anxiolytic activity? J Pharmacol Exp Ther 1994 Jan; 268: 248–54PubMedGoogle Scholar
  91. 91.
    Dunn RW, Carlezon Jr WA, Corbett R. Preclinical anxiolytic versus antipsychotic profiles of the 5-HT3 antagonists ondansetron, zacopride, 3α-tropanyl-lH-indole-3-carboxylic acid ester, and 1αH, 3α, 5-αH-tropan-3-yl-3,5-dichloro-benzoate. Drug Dev Res 1991; 23(4): 289–300CrossRefGoogle Scholar
  92. 92.
    Eglen RM, Lee CH, Khabbaz M, et al. Comparison of potencies of 5-HT3 receptor antagonists at inhibiting aversive behavior to illumination and the von Bezold-Jarisch reflex in the mouse. Neuropharmacology 1994 Feb; 33: 227–34PubMedCrossRefGoogle Scholar
  93. 93.
    Castejon AM, Aquino R, Cubeddu LX. Comparative effects of diazepam, chlordiazepoxide, buspirone and ondansetron in punished and unpunished responding in pigeons [abstract]. Can J Physiol Pharmacol 1994; 72 Suppl. 1: 363Google Scholar
  94. 94.
    Goudie AJ, Leathley MJ. Effects of the 5-HT3 antagonist GR38032F (ondansetron) on benzodiazepine withdrawal in rats. Eur J Pharmacol 1990 Aug 28; 185: 179–86PubMedCrossRefGoogle Scholar
  95. 95.
    Costall B, Jones BJ, Kelly ME, et al. The effects of ondansetron (GR38032F) in rats and mice treated subchronically with diazepam. Pharmacol Biochem Behav 1989 Dec; 34: 769–78PubMedCrossRefGoogle Scholar
  96. 96.
    Valdman EA, Garibova TL, Kalinina TS, et al. Effects of ondansetron and buspirone in benzodiazepine withdrawal syndrome. Behav Pharmacol 1996; 7 Suppl. 1: 114CrossRefGoogle Scholar
  97. 97.
    Mizoguchi H, Shirayama N, Tsuda M, et al. Potentiation of physical dependence on diazepam by ondansetron in rats. Life Sci 1994; 54(9): PL131–6PubMedCrossRefGoogle Scholar
  98. 98.
    Mizoguchi H, Suzuki T, Misawa M. Effects of serotonergic anxiolytics on physical dependence on diazepam in mice. Neurosci Lett 1993 Sep 17; 160: 41–4PubMedCrossRefGoogle Scholar
  99. 99.
    Goudie AJ, Leathley MJ. Effects of the 5-HT3 antagonist ondansetron on benzodiazepine-induced operant behavioural dependence in rats. Psychopharmacology 1992 Dec; 109: 461–5PubMedCrossRefGoogle Scholar
  100. 100.
    Prather PL, Rezazadeh SM, Lane JD, et al. Conflicting evidence regarding the efficacy of ondansetron in benzodiazepine withdrawal. J Pharmacol Exp Ther 1993 Feb; 264: 622–30PubMedGoogle Scholar
  101. 101.
    O’Hanlon JF, Vermeeren A, Uiterwijk MMC, et al. Anxiolytics’ effects on the actual driving performance of patients and healthy volunteers in a standardized test: an integration of three studies. Neuropsychobiology 1995; 31(2): 81–8PubMedCrossRefGoogle Scholar
  102. 102.
    van Veggel LMA, Preston C, O’Hanlon JF. Ondansetron and diazepam effects on actual driving and psychomotor performance. [abstract]. Neuropsychopharmacology 1994; 10 (3S Pt 2): 27S.Google Scholar
  103. 103.
    Hall ST, Ceuppens PR. A study to evaluate the effect of ondansetron on psychomotor performance after repeated oral dosing in healthy subjects. Psychopharmacology 1991; 104(1): 86–90PubMedCrossRefGoogle Scholar
  104. 104.
    Martin P, Gozlan H, Puech AJ. 5-HT3 receptor antagonists reverse helpless behaviour in rats. Eur J Pharmacol 1992 Feb 25; 212: 73–8PubMedCrossRefGoogle Scholar
  105. 105.
    Roila F, Del Favero A. Ondansetron clinical pharmacokinetics. Clin Pharmacokinet 1995 Aug; 29: 95–109PubMedCrossRefGoogle Scholar
  106. 106.
    Spahr-Schopfer IA, Lerman J, Sikich N, et al. Pharmacokinetics of intravenous ondansetron in healthy children undergoing ear, nose, and throat surgery. Clin Pharmacol Ther 1995 Sep; 58: 316–21PubMedCrossRefGoogle Scholar
  107. 107.
    Bozigian HP, Pritchard JF, Gooding AE, et al. Ondansetron absorption in adults: effect of dosage form, food, and antacids. J Pharm Sci 1994; 83(7): 1011–3PubMedCrossRefGoogle Scholar
  108. 108.
    Hsyu P-H, Pritchard JF, Bozigian HP, et al. Comparison of the pharmacokinetics of an ondansetron solution (8 mg) when administered intravenously, orally, to the colon, and to the rectum. Pharm Res 1994 Jan; 11: 156–9PubMedCrossRefGoogle Scholar
  109. 109.
    Simpson KH, Murphy P, Colthup PV, et al. Concentration of ondansetron in cerebrospinal fluid following oral dosing in volunteers. Psychopharmacology 1992 Dec; 109: 497–8PubMedCrossRefGoogle Scholar
  110. 110.
    Pritchard JF. Ondansetron metabolism and pharmacokinetics. Semin Oncol 1992; 19 Suppl. 10: 9–15PubMedGoogle Scholar
  111. 111.
    Dixon CM, Colthup PV, Serabjit-Singh CJ, et al. Multiple forms of cytochrome P450 are involved in the metabolism of ondansetron in humans. Drug Metab Dispos 1995 Nov; 23: 1225–30PubMedGoogle Scholar
  112. 112.
    Fischer V, Vickers AEM, Heitz F, et al. The polymorphic cytochrome P-4502D6 is involved in the metabolism of both 5-hydroxytryptamine antagonists, tropisetron and ondansetron. Drug Metab Dispos 1994 Mar–Apr; 22: 269–74PubMedGoogle Scholar
  113. 113.
    Ashforth EIL, Palmer JL, Bye A, et al. The pharmacokinetics of ondansetron after intravenous injection in healthy volunteers phenotyped as poor or extensive metabolisers of debrisoquine. Br J Clin Pharmacol 1994 Apr; 37: 389–91PubMedCrossRefGoogle Scholar
  114. 114.
    Blake JC, Palmer JL, Minton NA, et al. The pharmacokinetics of intravenous ondansetron in patients with hepatic impairment. Br J Clin Pharmacol 1993 Apr; 35: 441–3PubMedCrossRefGoogle Scholar
  115. 115.
    Figg WD, Dukes GE, Pritchard JF, et al. Pharmacokinetics of ondansetron in patients with hepatic insufficiency. J Clin Pharmacol 1996 Mar; 36: 206–15PubMedGoogle Scholar
  116. 116.
    Colthup PV, Felgate CC, Palmer JL, et al. Determination of ondansetron in plasma and its pharmacokinetics in the young and elderly. J Pharm Sci 1991 Sep; 80: 868–71PubMedCrossRefGoogle Scholar
  117. 117.
    Pritchard JF, Bryson JC, Kernodle AE, et al. Age and gender effects on ondansetron pharmacokinetics: evaluation of healthy aged volunteers. Clin Pharmacol Ther 1992; 51: 51–5PubMedCrossRefGoogle Scholar
  118. 118.
    Kennard D, Butcher M, Palmer J, et al. The anti-emetic efficacy, pharmacokinetics and safety of ondansetron in the elderly receiving cancer chemotherapy or radiotherapy. Eur J Cancer 1991; 27: S27Google Scholar
  119. 119.
    Sage TA, Jones WN, Clark RE Ondansetron in the treatment of intractable nausea associated with theophylline toxicity. Ann Pharmacother 1993 May; 27: 584–5PubMedGoogle Scholar
  120. 120.
    Daly D, Taylor JN. Ondansetron in theophylline overdose. Anaesth Intensive Care 1993 Aug; 21: 474–5PubMedGoogle Scholar
  121. 121.
    Roberts JR, Carney S, Boyle SM, et al. Ondansetron quells drug-resistant emesis in theophylline poisoning. Am J Emerg Med 1993 Nov; 11: 609–10PubMedCrossRefGoogle Scholar
  122. 122.
    Brown SGA, Prentice DA. Ondansetron in the treatment of theophylline overdose. Med J Aust 1992 Apr 6; 156: 512PubMedGoogle Scholar
  123. 123.
    Clark RF, Chen R, Williams SR, et al. The use of ondansetron in the treatment of nausea and vomiting associated with acetaminophen poisoning. J Toxicol Clin Toxicol 1996 Mar; 34: 163–7PubMedCrossRefGoogle Scholar
  124. 124.
    Tobias JD, Gregory DF, Deshpande JK. Ondansetron to prevent emesis following N-acetylcysteine for acetaminophen intoxication. Pediatr Emerg Care 1992 Dec; 8: 345–6PubMedCrossRefGoogle Scholar
  125. 125.
    Reed MD, Marx CM. Ondansetron for treating nausea and vomiting in the poisoned patient. Ann Pharmacother 1994 Mar; 28: 331–3PubMedGoogle Scholar
  126. 126.
    Dones I, Servello D, Ferrazza C, et al. Ondansentron as a treatment of intrathecal baclofen overdosage: a case report. J Neurology 1995; 242 Suppl. 2: 94Google Scholar
  127. 127.
    Gompels M, McWilliams S, Ohare M, et al. Ondansetron usage in HIV positive patients: a pilot study on the control of nausea and vomiting in patients on high dose co-trimoxazole for Pneumocystis-Carinii pneumonia. Int J STD AIDS 1993 Sep–Oct; 4: 293–6PubMedGoogle Scholar
  128. 128.
    Bailey J, Potokar J, Nutt D. Can the GI disturbance produced by SSRIs be attenuated by a 5-HT3 antagonist? [abstract]. Neuropsychopharmacology 1994 May; 10 Suppl. Pt 2: 220Google Scholar
  129. 129.
    Sullivan CA, Johnson CA, Roach H, et al. A pilot study of intravenous ondansetron for hyperemesis gravidarum. Am J Obstet Gynecol 1996; 174: 1565–8PubMedCrossRefGoogle Scholar
  130. 130.
    Guikontes E, Spantideas A, Diakakis J. Ondansetron and hyperemesis gravidarum. Lancet 1992 Nov 14; 340: 1223PubMedCrossRefGoogle Scholar
  131. 131.
    Andrews PA, Quan V, Ogg CS. Ondansetron for symptomatic relief in terminal uraemia. Nephrol Dial Transplant 1995; 10(1): 140PubMedGoogle Scholar
  132. 132.
    Andrews PA. Use of ondansetron, a new antiemetic, in uremia. Semin Dialysis 1995 Jul–Aug; 8: 245–6CrossRefGoogle Scholar
  133. 133.
    Kleinerman KB, Deppe SA, Sargent AI. Use of ondansetron for control of projectile vomiting in patients with neurosurgical trauma: two case reports. Ann Pharmacother 1993 May; 27: 566–8PubMedGoogle Scholar
  134. 134.
    Abell TL, Werkman R, Voeller G, et al. Long-term therapy with ondansetron is effective in patients with refractory nausea and vomiting [abstract]. Gastroenterology 1995 Apr; 108 Suppl.: 1CrossRefGoogle Scholar
  135. 135.
    Tobias JD. Ondansetron: indications and applications in the paediatric intensive care unit. Anaesth Intensive Care 1992 Nov; 20: 504–6PubMedCrossRefGoogle Scholar
  136. 136.
    von-der-Ohe MR, Camilleri M, Kvols LK. A 5HT3 antagonist corrects the postprandial colonic hypertonic response in carcinoid diarrhea. Gastroenterology 1994 May; 106: 1184–9PubMedGoogle Scholar
  137. 137.
    Leijsma JK, Kleibeuker JH, Sleijfer DT, et al. Effects of ondansetron on symptoms and gastric emptying in carcinoid patients [abstract]. Proc Am Soc Clin Oncol 1994 Mar; 13: 190Google Scholar
  138. 138.
    Schwörer H, Münke H, Stöckmann F, et al. Treatment of diarrhea in carcinoid syndrome with ondansetron, tropisetron, and clonidine. Am J Gastroenterol 1995 Apr; 90: 645–8PubMedGoogle Scholar
  139. 139.
    Platt AJ, Heddle RM, Rake MO, et al. Ondansetron in carcinoid syndrome. Lancet 1992 Jun 6; 339: 1416PubMedCrossRefGoogle Scholar
  140. 140.
    Steadman CJ, Talley NJ, Phillips SF, et al. Selective 5-hydroxytryptamine type 3 receptor antagonism with ondansetron as treatment for diarrhea-predominant irritable bowel syndrome: a pilot study. Mayo Clin Proc 1992 Aug; 67: 732–8PubMedCrossRefGoogle Scholar
  141. 141.
    Maxton DG, Morris J, Whorwell PJ. Selective 5-hydroxytrypt-amine antagonism: a role in irritable bowel syndrome and functional dyspepsia. Aliment Pharmacol Ther 1996; 10: 595–9PubMedCrossRefGoogle Scholar
  142. 142.
    Hammer J, Phillips SF, Talley NJ, et al. Effect of a 5HT3-antagonist (ondansetron) on rectal sensitivity and compliance in health and the irritable bowel syndrome. Aliment Pharmacol Ther 1993 Oct; 7: 543–51PubMedCrossRefGoogle Scholar
  143. 143.
    Goldberg PA, Kamm MA, Setti-Carraro P, et al. 5HT3 antagonism (ondansetron) does not modify visceral sensation, bowel compliance or symptoms in healthy subjects or irritable bowel patients [abstract]. Gut 1993; 34(4) Suppl.: 55Google Scholar
  144. 144.
    Schwörer H, Hartmann H, Ramadori G. Treatment of chronic cryptosporidiosis-induced diarrhea with a serotonin receptor antagonist. Am J Gastroenterol 1994 Mar; 89: 458PubMedGoogle Scholar
  145. 145.
    Nielsen OH, Hvid-Jacobsen K, Lund P, et al. Gastric emptying and subjective symptoms of nausea: lack of effects of a 5-hydroxytryptamine-3 antagonist ondansetron on gastric emptying in patients with gastric stasis syndrome. Digestion 1990 Jun; 46: 89–96PubMedCrossRefGoogle Scholar
  146. 146.
    Bossi A, Baresi A, Ballini A, et al. Ondansetron in the treatment of diabetic diarrhea. Diabetes Care 1994 May; 17: 453–4PubMedGoogle Scholar
  147. 147.
    Evans JE. Nausea, abdominal pain and diarrhoea of uncertain cause responding to ondansetron. Med J Aust 1993 Jul 19; 159: 125–7PubMedGoogle Scholar
  148. 148.
    Schwörer H, Ramadori G. Treatment of pruritus: a new indication for serotonin type 3 receptor antagonists. Clin Investig 1993 Aug; 71: 659–62PubMedCrossRefGoogle Scholar
  149. 149.
    Raderer M, Müller C, Scheithauer W. Ondansetron for pruritus due of cholestasis. N Engl J Med 1994 May 26; 330: 1540PubMedCrossRefGoogle Scholar
  150. 150.
    Schwörer H, Hartmann H, Ramadori G. Relief of cholestatic pruritus by a novel class of drugs: 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists: effectiveness of ondansetron. Pain 1995 Apr; 61: 33–7PubMedCrossRefGoogle Scholar
  151. 151.
    Crighton IM, Hobbs GJ, Reid MF. Ondansetron for the treatment of pruritis after spinal opioids. Anaesthesia 1996 Feb; 51: 199–200PubMedCrossRefGoogle Scholar
  152. 152.
    Schwörer H, Ramadori G. Treatment of acute gouty arthritis with the 5-hydroxytryptamine antagonist ondansetron. Clin Investig 1994 Oct; 72: 811–3PubMedCrossRefGoogle Scholar
  153. 153.
    Hrycaj P, Stratz T, Mennet P, et al. Pathogenetic aspects of responsiveness to ondansetron (5-hydroxytryptamine type 3 receptor antagonist) in patients with primary fibromyalgia syndrome — a preliminary study. J Rheumatol 1996; 23: 1418–23PubMedGoogle Scholar
  154. 154.
    Stratz T, Schochat T, Hrycaj P, et al. Therapy of fibromyalgia by blocking of S3 receptors [in German]. Z Rheumatol 1994 Nov–Dec; 53: 335–8PubMedGoogle Scholar
  155. 155.
    Sellers EM, Toneatto T, Romach MK, et al. Clinical efficacy of the 5-HT3 antagonist ondansetron in alcohol abuse and dependence. Alcohol Clin Exp Res 1994 Aug; 18: 879–85PubMedCrossRefGoogle Scholar
  156. 156.
    Loimer N, Hofmann P, Chaudhry H. Ultrashort noninvasive opiate detoxification [letter]. Am J Psychiatry 1993 May; 150: 839PubMedGoogle Scholar
  157. 157.
    Sell LA, Cowen PJ, Robson PJ. Ondansetron and opiate craving: a novel pharmacological approach to addiction. Br J Psychiatry 1995 Apr; 166: 511–4PubMedCrossRefGoogle Scholar
  158. 158.
    Rice GPA, Ebers GC. Ondansetron for intractable vertigo complicating acute brainstem disorders. Lancet 1995 May 6; 345: 1182–3PubMedCrossRefGoogle Scholar
  159. 159.
    Rice G, Dickey C, Lesaux J, et al. Ondansetron for disabling cerebellar tremor [abstract]. Ann Neurol 1995 Dec; 38: 973Google Scholar
  160. 160.
    Zoldan J, Friedberg G, Weizman A, et al. Zofran Rm (ondansetron), a 5-HT3 receptor antagonist: administration in 16 patients with Parkinson’s disease and levodopa-associated psychosis [abstract]. Neurology 1994 Apr; 44 Suppl. 2: 254Google Scholar
  161. 161.
    Zoldan J, Friedberg G, Weizman A, et al. Psychosis in levodopa-treated Parkinsonian patients: clinical features and response to ondansetron, a selective 5-HT3 antagonist [abstract]. Neurology 1995 Apr; 45 Suppl. 4: 167Google Scholar
  162. 162.
    López del Val LJ, Jericó Pascual I, López del Val JA. Treatment of hallucinations with ondansetron in 23 patients with advanced Parkinson’s disease. Mov Disord 1996; 11 Suppl. 1: 193Google Scholar
  163. 163.
    Zoldan J, Friedberg G, Weizman A, et al. Recurrent acute psychosis following repeated trials of levodopa initiation in de novo patients with Parkinson’s disease: reversal of intolerance by preparatory pretreatment with ondansetron, a 5-HT3 antagonist [abstract], Mov Disord 1995 Sep; 10: 694Google Scholar
  164. 164.
    White A, Corn TH, Feetham C, et al. Ondansetron in treatment of schizophrenia. Lancet 1991 May 11; 337: 1173PubMedCrossRefGoogle Scholar
  165. 165.
    Mathew RJ, Wilson WH. Evaluation of the effects of diazepam and an experimental anti-anxiety drug on regional cerebral blood flow. Psychiatry Res Neuroimaging 1991 Oct; 40: 125–34CrossRefGoogle Scholar
  166. 166.
    Plosker GL, Milne RJ. Ondansetron: a pharmacoeconomic and quality-of-life evaluation of its antiemetic activity in patients receiving cancer chemotherapy. PharmacoEconomics 1992; 2(4): 285–304PubMedCrossRefGoogle Scholar
  167. 167.
    Krstenansky PM, Petree J, Long G. Extrapyramidal reaction caused by ondansetron [letter]. Ann Pharmacother 1994 Feb; 28: 280PubMedGoogle Scholar
  168. 168.
    Camp-Sorrell D. Managing an extrapyramidal reaction caused by ondansetron. Oncol Nurs Forum 1995 May; 22: 718–9PubMedGoogle Scholar
  169. 169.
    Mathews IIIHG, Tancil CG. Extrapyramidal reaction caused by ondansetron. Ann Pharmacother 1996 Feb; 30: 196PubMedGoogle Scholar
  170. 170.
    Jacobsen MB. Ondansetron in carcinoid syndrome [letter]. Lancet 1992 Jul 18; 340: 185PubMedCrossRefGoogle Scholar
  171. 171.
    Sargent AI, Deppe SA, Chan FA. Seizure associated with ondansetron. Clin Pharm 1993 Aug; 12: 613–5PubMedGoogle Scholar
  172. 172.
    Mitchell KE, Popkin MK, Trick W, et al. Psychiatric complications associated with ondansetron. Psychosomatics 1994 Mar–Apr; 35: 161–3PubMedCrossRefGoogle Scholar
  173. 173.
    Oren DA. Dysphoria after treatment with ondansetron [letter]. Am J Psychiatry 1995 Jul; 152: 1101PubMedGoogle Scholar
  174. 174.
    Chen M, Tanner A, Gallo-Torres H. Anaphylactoid-anaphylactic reactions associated with ondansetron [letter]. Ann Intern Med 1993 Oct 15; 119: 862PubMedGoogle Scholar
  175. 175.
    Madera J, Sanz S, Pérez CI, et al. Urticaria and angioedema caused by ondansetrom. Allergy 1995; 50 Suppl. 26: 214Google Scholar
  176. 176.
    Kossey JL, Kwok KK. Anaphylactoid reactions associated with ondansetron. Ann Pharmacother 1994 Sep; 28: 1029–30PubMedGoogle Scholar
  177. 177.
    Verrill M, Judson I. Jaundice with ondansetron. Lancet 1994 Jul 16; 344: 190–1PubMedCrossRefGoogle Scholar
  178. 178.
    Heyman JS, Young ML, Bagshaw RJ, et al. Cardiovascular stability with rapid intravenous infusion of ondansetron. Can J Anaesth 1993 May; 40 (Pt 1): 448–52PubMedGoogle Scholar
  179. 179.
    Rose JB, McCloskey JJ. Rapid intravenous administration of ondansetron or metoclopramide is not associated with cardiovascular compromise in children. Paediatr Anaesth 1995; 5(2): 121–4PubMedCrossRefGoogle Scholar
  180. 180.
    Johnson BA, Rue J, Cowen PJ. Ondansetron and alcohol pharmacokinetics. Psychopharmacology 1993 Aug; 112: 145PubMedCrossRefGoogle Scholar
  181. 181.
    Capacio B, Byers CE, Matthews RL. Effect of pyridostigmine on pharmacokinetics of the 5-HT3 receptor antagonist ondansetron [abstract]. FASEB J 1993 Feb 23; 7 (Pt II): A699Google Scholar
  182. 182.
    Sullivan CA, Johnson CA, Roach H, et al. A prospective, randomized, double-blind comparison of the serotonin antagonist ondansetron to a standardized regimen of promethazine for hyperemesis gravidarum. A preliminary investigation [abstract]. Am J Obstet Gynecol 1995 Jan; 172 (Pt 2): 299Google Scholar
  183. 183.
    World MJ. Ondansetron and hyperemesis gravidarum [letter]. Lancet 1993 Jan 16; 341: 185PubMedCrossRefGoogle Scholar
  184. 184.
    Maxton DG, Haigh CG, Whorwell PJ. Clinical trial of ondansetron, a selective 5HT3 antagonist in irritable bowel syndrome [abstract]. Gastroenterology 1991 May; 100 (Pt 2) Suppl.: A468Google Scholar
  185. 185.
    Schwörer H, Ramadori G. Improvement of cholestatic pruritus by ondansetron. Lancet 1993 May 15; 341: 1277PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 1996

Authors and Affiliations

  • Michelle I. Wilde
    • 1
  • Anthony Markham
    • 1
  1. 1.Adis International LimitedMairangi Bay, Auckland 10New Zealand

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