Antiemetic Efficacy of High-Dose Metoclopramide: Randomized Trials with Placebo and Prochlorperazine in Patients with Chemotherapy-Induced Nausea and Vomiting

Gralla, Richard J.; Itri, Loretta M.; Pisko, Sharon E.; Squillante, Anna E.; Kelsen, David P.; Braun, David; Bordin, Laurie A.; Braun, Thomas J.; Young, Charles W.

doi:10.1056/nejm198110153051601

Cited by 676 publications

(160 citation statements)

References 13 publications

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“…In the objective assessment we did not find the measurement of volume of vomitus to be sufficiently reliable to include in the analysis, as others have attempted (Gralla et al, 1981); the volume is also probably of less relevance to the patients than the number of vomiting or retching episodes.…”

Section: Discussionmentioning

confidence: 75%

“…Newer agents being evaluated are high-dose metoclopramide, dexamethasone and the cannabinoids (Gralla et al, 1981;Trounce, 1982). Most controlled studies of the latter have hitherto been conducted in the United States; those of nabilone have demonstrated useful oral efficacy and superiority over oral prochlorperazine in mixed groups of patients with various malignancies on different chemotherapeutic regimes (Herman et al, 1979;Steele et al, 1980).…”

Section: Discussionmentioning

confidence: 99%

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Anti-emetic efficacy and toxicity of nabilone, a synthetic cannabinoid, in lung cancer chemotherapy

Ahmedzai¹,

Carlyle²,

Calder³

et al. 1983

Br J Cancer

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Section: Discussionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Anti-emetic efficacy and toxicity of nabilone, a synthetic cannabinoid, in lung cancer chemotherapy

Ahmedzai¹,

Carlyle²,

Calder³

et al. 1983

Br J Cancer

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“…Modern medicine is particularly effective at provoking nausea and vomiting, including many drug treatments and post surgery recovery. A significant impetus to develop anti-emetic drugs originated from a desire to inhibit nausea and vomiting produced by some anti-cancer agents with high emetic potential, such as cisplatin (Gralla et al, 1981). An assortment of other drugs also have side effects of nausea and vomiting in prescribed doses, and many drugs will produce these effects at high dosages.…”

Section: Why Are Nausea and Vomiting Important In Today's World?mentioning

confidence: 99%

Why is the neurobiology of nausea and vomiting so important?

2008

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Nausea and vomiting are important as biological systems for drug side effects, disease co-morbidities, and defenses against food poisoning. Vomiting can serve the function of emptying a noxious chemical from the gut, and nausea appears to play a role in a conditioned response to avoid ingestion of offending substances. The sensory pathways for nausea and vomiting, such as gut and vestibular inputs, are generally defined but the problem of determining the brain's final common pathway and central pattern generator for nausea and vomiting is largely unsolved. A neurophysiological analysis of brain pathways provides an opportunity to more closely determine the neurobiology of nausea and vomiting and its prodromal signs (e.g., cold sweating, salivation).

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“…Firstly, it was found that, unlike conventional doses of metoclopramide (Maxolon; Beecham Pharmaceuticals) which antagonise dopamine receptors and stimulate gastric motility, high doses of the drug greatly reduced cis-platin-evoked emesis (Gralla et al, 1981). In contrast, even high doses of the dopamine antagonists, domperidone (Motilium; Janssen Pharmaceuticals) or alizapride, have little or no ability to prevent cis-platininduced emesis (Tonato et al, 1985;Saller & Hellenbrecht, 1985).…”

mentioning

confidence: 99%

Evidence that 5-hydroxytryptamine3 receptors mediate cytotoxic drug and radiation-evoked emesis

Miner

Sanger²,

Turner³

1987

Br J Cancer

113

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Summary The involvement of 5-hydroxytryptamine (5-HT) 5-HT3 receptors in the mechanisms of severe emesis evoked by cytotoxic drugs or by total body irradiation have been studied in ferrets. Anti-emetic compounds tested were domperidone (a dopamine antagonist), metoclopramide (a gastric motility stimulant and dopamine antagonist at conventional doses, a 5-HT3 receptor antagonist at higher doses) and BRL 24924 (a potent gastric motility stimulant and a 5-HT3 receptor antagonist). Domperidone or metoclopramide prevented apomorphine-evoked emesis, whereas BRL 24924 did not. Similar doses of domperidone did not prevent emesis evoked by cis-platin or by total body irradiation, whereas metoclopramide or BRL 24924 greatly reduced or prevented these types of emesis. Metoclopramide and BRL 24924 also prevented emesis evoked by a combination of doxorubicin and cyclophosphamide. These results are discussed in terms of a fundamental role for 5-HT3 receptors in the mechanisms mediating severely emetogenic cancer treatment therapies.There have recently been two important advances relating to the improvement of anti-emetic treatment given to patients undergoing anti-cancer therapies. Firstly, it was found that, unlike conventional doses of metoclopramide (Maxolon; Beecham Pharmaceuticals) which antagonise dopamine receptors and stimulate gastric motility, high doses of the drug greatly reduced cis-platin-evoked emesis (Gralla et al., 1981). In contrast, even high doses of the dopamine antagonists, domperidone (Motilium; Janssen Pharmaceuticals) or alizapride, have little or no ability to prevent cis-platininduced emesis (Tonato et al., 1985;Saller & Hellenbrecht, 1985). Mechanisms other than dopamine receptor antagonism have therefore been implicated in this antiemetic action of metoclopramide (McRitchie et al., 1984).Secondly, metoclopramide is an antagonist of 5-hydroxytryptamine (5-HT) acting on 5-HT3 receptors (previously known as 5-HT M-receptors; see Bradley et al., 1986 for definition of this receptor) located in the peripheral nervous system (Fozard, 1984a); the effective concentrations of metoclopramide are higher than those required to antagonise dopamine receptors or to stimulate gut motility (Sanger, 1984). We subsequently suggested that such high doses of metoclopramide may prevent cis-platin-induced emesis by means of antagonising 5-HT3 receptors .The involvement of 5-HT3 receptors in the mechanisms of emesis have now been further investigated using chemo-and radio-emetic stimuli in the ferret. The ferret has previously been shown to be suitable for studying emesis evoked by cisplatin (Florczyk et al., 1982;), a combination of doxorubicin and cyclophosphamide (Schurig et al., 1984) or by whole-body irradiation (Andrews et al., 1986;Gylys & Gidda, 1986

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Antiemetic Efficacy of High-Dose Metoclopramide: Randomized Trials with Placebo and Prochlorperazine in Patients with Chemotherapy-Induced Nausea and Vomiting

Cited by 676 publications

References 13 publications

Anti-emetic efficacy and toxicity of nabilone, a synthetic cannabinoid, in lung cancer chemotherapy

Anti-emetic efficacy and toxicity of nabilone, a synthetic cannabinoid, in lung cancer chemotherapy

Why is the neurobiology of nausea and vomiting so important?

Evidence that 5-hydroxytryptamine3 receptors mediate cytotoxic drug and radiation-evoked emesis

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