Metoclopramide

Harrington, RA; Hamilton, Cindy W.; Brogden, Rex N.; Linkewich, Joseph A.; Romankiewicz, John A.; Heel, R. C.

doi:10.2165/00003495-198325050-00002

Cited by 334 publications

(22 citation statements)

References 148 publications

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“…However, the inability of conventional doses of metoclopramide or of domperidone to inhibit cis-platin-evoked emesis is in marked conflict with this suggestion. At these doses, both drugs have been shown to stimulate gut motility in man and a variety of small laboratory animals (Brogden et al, 1982;Harrington et al, 1983). The gastric prokinetic activity of metoclopramide and BRL 24924 may, nevertheless, prevent nausea and vomiting associated with other conditions.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…1 4 This was attributed to the short duration of effect of the drug. 10,14 Thus, we decided to give a second dose of both drugs six hours after the first administration since the plasma half life of both drugs, metoclopramide and dimenhydrinate, is similar (about 4-6 hr 15,16 ).…”

Section: Discussionmentioning

confidence: 99%

Dimenhydrinate and metoclopramide alone or in combination for prophylaxis of PONV

Eberhart

Seeling

Ulrich

et al. 2000

Can J Anesth/J Can Anesth

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Purpose: Dimenhydrinate and metoclopramide are inexpensive antiemetic drugs. Metoclopramide, especially, has been studied extensively in the past, but there are no studies on the combination of both drugs for prevention of postoperative nausea and vomiting (PONV).Methods: One hundred and sixty male inpatients undergoing endonasal surgery were randomized to receive one of four antiemetic regimens in a double-blind manner: placebo, 1 mg·kg -1 dimenhydrinate, 0.3 mg·kg -1 metoclopramide, or the combination of both drugs was administered after induction of anesthesia. Patients received a second dose of these drugs six hours after the first administration to mitigate their short half-life. Standardized general anesthesia included benzodiazepine premedication, propofol, desflurane in N 2 O/O 2 vecuronium, and a continuous infusion of remifentanil. Postoperative analgesia and antiemetic rescue medication were standardized. Episodes of vomiting, retching, nausea, and the need for additional antiemetics were recorded for 24 hr. The incidences of PONV were analyzed with Fisher´s Exact test and the severity of PONV (rated by a standardized scoring algorithm) with the Jonckheere-Terpestra-test. Results:The incidence of patients free from PONV was 62.5% in the placebo-group and increased to 72.5% in the metoclopramide-group (P = 0.54), 75.0% in the dimenhydrinate-group (P = 0.34), and 85.0% in the combination-group (P = 0.025). In the latter group, the severity of PONV was reduced compared with placebo treatment (P = 0.017; Jonckheere-Terpestra-test).Conclusion: Dimenhydrinate and metoclopramide were ineffective in reducing the incidence and the severity of PONV. Their combination reduced the incidence of PONV compared with placebo.Objectif : Le dimenhydrinate et le métoclopramide sont des antiémétiques pas chers. Beaucoup d'études ont déjà été faites, avec le métoclopramide surtout, mais aucune avec la combinaison des deux comme moyen de prévention des nausées et des vomissements postopératoires (NVPO).Méthode : Cent soixante patients masculins qui devaient subir une intervention endonasale ont consenti à participer à une étude prospective, randomisée et en double aveugle, et à recevoir un des quatre traitements antiémétiques suivants : un placebo; 1 mg·kg-1 de dimenhydrinate; 0,3 mg·kg-1 de métoclopramide ou une combinaison des deux médicaments après l'induction de l'anesthésie. Ceux qui ont reçu du dimenhydrinate ou les deux médicaments ont eu une seconde dose de dimenhydrinate six heures après la première étant donné la courte demi-vie de ce médicament. L'anesthésie générale standardisée comprenait une prémédication de benzodiazépine, du propofol, du desflurane dans un mélange de N 2 O/O 2 , du vécuronium et une perfusion continue de rémifentanil. L'analgésie postopératoire et les antiémétiques de rattrapage ont été standardisés. Les nausées, les vomissements, les efforts pour vomir et les demandes d'antiémétiques additionnels ont été enregistrés pendant 24 h. Les incidences de NVPO ont été analysées selon le test Exact ...

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“…In 2 = In a + n In C C, = Ae-"t + Be-0' (2) where C is the plasma concentration at time t, a and p are the apparent distribution and terminal elimination rate constants, respectively, and A and B are the intercepts of the a and p phases, …”

Section: "Cmentioning

confidence: 99%