Drugs

, Volume 12, Issue 2, pp 81–131

Metoclopramide: A Review of its Pharmacological Properties and Clinical Use

  • R. M. Pinder
  • R. N. Brogden
  • Phyllis R. Sawyer
  • T. M. Speight
  • G. S. Avery
Evaluations on New Drugs

Summary

Synopsis: Metoclopramide 1 , 4-amino-5-chlorO’2-methoxy-N-(2-diethyl-aminoethyl) benzamide, is advocated for use in gastro-intestinal diagnostics, and in treating various types of vomiting and a variety of functional and organic gastro-intestinal disorders.

Published data have indicated that metoclopramide assists radiological identification of lesions in the small intestine, facilitates duodenal intubation and small intestine biopsy, and eases emergency endoscopy in upper gastro-intestinal haemorrhage. Metoclopramide reduces post-operative vomiting and radiation sickness, and ameliorates some types of drug-induced vomiting. It may provide symptomatic relief in dyspepsia and possibly in vertigo, reflux oesophagitis and hiccups, but further controlled trials are needed to confirm the efficacy of metoclopramide in these proposed areas of use. It promotes gastric emptying prior to anaesthesia. Its effects in healing gastric ulcer and preventing relapse of duodenal ulcer remain unproven.

Side-effects are few and transient, though alarming extrapyramidal reactions can occur in a small proportion of patients receiving therapeutic doses but more usually following excessive doses in young subjects. They respond rapidly to withdrawal of the drug.

Pharmacodynamic studies in man and in a variety of experimental animals have established that metoclopramide, after oral or intravenous administration, rapidly affects the motility of the gastro-intestinal tract. Its effects include improved resting tone of the oesophageal sphincter, improved tone and peristalsis of the stomach with accelerated gastric emptying (but with slowing in some cases), enhanced pyloric activity, distension of the duodenal bulb, and increased peristalsis of the duodenum with accelerated transit through the duodenum and jejunum. It has comparatively little overall effect on colonic motor activity in vivo. The actions of metoclopramide on motility are blocked by atropine and can be reproduced in vitro on animal and human smooth muscle. It is unclear whether the drug is effective in all post-vagotomy patients. Metoclopramide has no effect on gastric secretion, and may sensitise gut muscle to the action of endogenous acetylcholine.

The accelerated gastric emptying usually produced by metoclopramide is reflected in its effects on the absorption of other drugs. Intramuscular metoclopramide promoted the absorption of salicylate from the depressed levels associated with attacks of migraine to those characteristic of normal subjects. Paracetamol absorption was both accelerated and enhanced in normal subjects. Metoclopramide also accelerated absorption of tetracycline and pivampicillin, ethanol, and levodopa, but did not affect that of isoniazid. The absorption of digoxin from slow-release tablets was depressed by multiple doses of metoclopramide given to patients on maintenance digoxin therapy.

Metoclopramide is effective in preventing apomorphine-induced vomiting in man, and appears to be equipotent with prochlorperazine but superior to trimethobenzamide. In animals it is a potent antagonist of vomiting induced by apomorphine, hydergine, reserpine, tetrodotoxin and copper sulphate. Metoclopramide has behavioural properties in animals which suggest that it is a central dopaminergic antagonist, and it may exert its anti-emetic effects by blocking the chemoreceptor trigger zone for vomiting. In cats, spontaneous electrical discharges from this part of the central nervous system were abolished by metoclopramide and stimulated by apomorphine. Other effects of metoclopramide on the central nervous system include typical neuroleptic properties in animals; catalepsy and reversal of the behavioural stereotypies produced by apomorphine or amphetamine. In man, however, metoclopramide is without significant antipsychotic or sedative properties.

Metoclopramide lacks significant cardiovascular effects, and large intravenous doses in patients with heart disease had no marked influence on haemodynamic parameters. Intracardiac conduction is unaffected by metoclopramide, though large doses prevent experimentally-induced cardiac arrhythmias in animals and produce a slight and transient decrease in blood pressure. Metoclopramide has a negligible effect on blood pressure responses in animals to acetylcholine, adrenaline, histamine and noradrenaline but it blocks the hypotensive action of dopamine.

Pharmacokinetic studies of metoclopramide in man are limited, but animal experiments suggest that the drug is well absorbed and rapidly excreted, with a short half-life and only partial metabolism by O-demethylation, N-de-ethylation and amide hydrolysis. Maximum plasma levels occur within 30 to 120 minutes of oral dosage, and human studies indicate that levels of 0.2gmg/ml are achieved following intramuscular doses of 40mg. Plasma half-life in animals is 1 to 2 hours, and metoclopramide is distributed principally to the intestinal mucosa, liver, biliary tract, and salivary glands. Within the central nervous system the drug is localised at the area postrema, which contains the chemoreceptor trigger zone for vomiting. Metoclopramide binds only moderately to human plasma protein and 24% of the dose was excreted unchanged in the first 24 hours following an intramuscular dose of 40mg in human volunteers.

Therapeutic trials under controlled conditions have shown that metoclopramide in intramuscular doses of 10 to 20mg is significantly better than placebo in controlling postoperative vomiting. Metoclopramide was also slightly more effective than prochlorperazine (10mg, im) in one study and significantly superior to perphenazine (5mg, im) in one of two studies but there was no significant difference between metoclopramide (20mg, iv) and trimethobenzamide (300mg, iv). The effects of metoclopramide seem to be independent of either the type of anaesthetic or the premedicant used but for optimum effect may need to be given towards the end of the operation. Controlled trials have demonstrated that 10mg intramuscular metoclopramide is significantly superior to placebo, perphenazine (5mg, im), or prochlorperazine (10mg, im) in preventing vomiting due to pethidine or morphine. The drug was effective in women during labour, in the elderly, and in surgical patients, and it abolished pre-operative vomiting associated with pethidine administration. Clinical experience suggests that daily doses of 30 to 80mg metoclopramide are effective in controlling nausea and vomiting in Parkinsonian patients receiving levodopa, without compromising the therapeutic efficacy of levodopa. However, controlled trials show that the drug has no place in relieving emesis induced by some cytostatic drugs or by iodipamide.

Radiation sickness was ameliorated by daily metoclopramide, which was not significantly different in its effect from prochlorperazine. Metoclopramide was indistinguishable from prochlorperazine and significantly superior to placebo in a controlled trial in the relief of vomiting of pregnancy, without apparent deleterious effects on the fetus. Clinical experience confirms these effects, but like all new drugs metoclopramide should probably not be given to women during the first 3 months of pregnancy since its safety in use has not been established, despite the lack of dysmorphogenic effects in animals. Limited controlled trials show that metoclopramide may be useful in providing symptomatic relief, particularly from nausea and vomiting, in patients with a variety of disorders. Further controlled trials in large groups of selected patients are needed to confirm these effects.

Results of a controlled study indicate that metoclopramide may be effective in treating nausea and vomiting of vertigo and certain associated disorders, but it appears to have no place in the treatment of seasickness. Migraine may respond to the drug, but in the studies to date patients have continued to take their usual analgesic medication, the absorption of which is promoted by metoclopramide. The lack of sufficient controlled trials, however, leaves the role of metoclopramide in these disorders uncertain.

Dyspepsia responds to metoclopramide, which was significantly superior to placebo or the anticholinergic drug pipenzolate in controlled trials. Metoclopramide was more effective in controlling nausea, vomiting, epigastric burning, heartburn, and regurgitation of sour fluid than the flatulent symptoms of belching, bloating, and abdominal distension. Nevertheless, there is still some debate as to whether metoclopramide is effective in preventing gastro-oesophageal reflux. Metoclopramide may be useful in treating hiccup.

Limited controlled trials suggest that metoclopramide provides symptomatic relief and may accelerate the healing of gastric ulcer and prevent relapse of duodenal ulcer, but its role remains unproven. Some functional gastro-intestinal disorders appear to respond to metoclopramide. In controlled trials, it was significantly more effective than carbachol or placebo in relieving post-vagotomy gastric stasis, superior to placebo in alleviating gastritis and gastroptosis, and as effective as isopropamide plus haloperidol against irritable colon and spastic constipation. It has been used successfully in the conservative management of complete pyloric obstruction due to duodenal ulcer, in order to avoid emergency surgery but it probably should not be used in pyloric stenosis due to carcinoma or severe fibrosis.

The dual action of metoclopramide in preventing emesis and accelerating gastric emptying, has established its use in anaesthetic practice. It is especially useful in emergency anaesthesia, including during labour, when rapid clearance of gastric contents is required.

Diagnostic uses: In diagnostic radiology or cineradiology, metoclopramide given before barium meal provides excellent conditions for the diagnosis of lesions in the duodenum, jejunum and ileum, and prevents vomiting of barium in nauseated patients such as those with jaundice. It significantly increases the rate of gastric emptying and reduces the transit time for barium to reach the caecum. Controlled trials have shown that small intestine examinations are complete within 1 hour in over 80% of metoclopramide-treated patients compared with in less than 20% of untreated patients. Both oral and intravenous metoclopramide were superior to placebo in speeding gastric emptying and reducing the number of films needed for complete visualisation of the small intestine, but in one study oral metoclopramide gave an increased number of radiographically poor examinations.

Metoclopramide is useful in facilitating duodenal intubation ad permitting rapid and successful biopsy of the small intestine, in the absence of significant side-effects. It speeds the passage of biopsy capsules across the pylorus, and was significantly superior to both placebo and pharyngeal anaesthesia in controlled trials. In patients with functional pyloric stenosis, metoclopramide facilitated endoscopic observation of the duodenal bulb.

Emergency endoscopy of upper gastro-intestinal haemorrhage is facilitated by the administration of metoclopramide, which clears the viewing area of blood. However, it is possible that the increased stomach activity may in itself cause further haemorrhage.

Side-effects with metoclopramide are usually mild, transient, and readily reversed by withdrawal of drug. A review of one published trial suggests that they occur in about 11% of patients, but the incidence may be different in clinical practice. They consist principally of drowsiness and lassitude, bowel disturbances, and dizziness and faintness. Metoclopramide may increase lactation by stimulating the release of prolactin.

Extrapyramidal effects are alarming but uncommon (in about 1% of patients). They consist of dystonic reactions such as trismus, torticollis, facial spasms, opisthotonos, and oculogyric crises, but Parkinsonian-like symptoms are absent. Metoclopramide-induced dystonia occurs more often in females and in the young patient; when it occurs it is usually following excessive doses, but may also occur at normal therapeutic dosage, and resembles in many respects the dyskinesias induced by the phenothiazines. It responds readily to withdrawal of drug, but severe cases may benefit from intramuscular benztropin or diazepam. Children are particularly susceptible, but restriction of the daily dose to 0.5mg/kg usually prevents overdosage in young patients. Signs of overdosage in children usually include extreme irritability and agitation, with muscle hypertonia. Two adult cases of attempted suicide with 360 and 800mg metoclopramide recovered uneventfully following gastric lavage and observation; somnolence and disorientation were reported, but there were no extrapyramidal signs.

Contra-indications and precautions: Metoclopramide should neither be given with, or within 2 weeks of treatment with monoamine oxidase inhibitors, tricyclic antidepressants, or sympathomimetic drugs, nor to women in the first 3 months of pregnancy, as the safety of use of such associations has not been established. It may potentiate the central action of some antipyschotic drugs, and its own action on the gastro-intestinal tract may be potentiated by acetylcholine-like drugs and blocked by atropine-like agents. It should not be given with phenothiazines.

The ability of metoclopramide to provide symptomatic relief in gastro-intestinal disorders does not replace proper investigation and diagnosis of the patient’s symptoms. Metoclopramide should not be given to patients with epilepsy or extrapyramidal syndromes, though it may be safely used in Parkinsonian patients to control vomiting. The dosage for children should be carefully adjusted from initially low levels. Increasing the adult dosage beyond the recommended level does not normally lead to a corresponding enhancement of therapeutic effects.

Dosage: Metoclopramide is given before or just after meals, or 20 minutes before symptoms are likely to occur, in oral, intramuscular, or intravenous doses of 10mg, up to 3 times daily, in adults, and 5 to 10mg 2 to 3 times daily in young adults. Children under 14 should receive 1 to 5mg, 2 to 3 times daily, according to age and body weight. The total daily dose in children and young adults should not exceed 0.5mg/kg.

For diagnostic purposes, the adult dose is 20mg orally, 20 minutes before examination, or 10 to 20mg by injection 5 minutes before examination. Children receive, according to age and body weight, 1 to 5mg, 5 to 10 minutes before examination.

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References

  1. Ahtee, L. and Buncombe, G.: Metoclopramide induces catalepsy and increases striatal homovanillic acid content in mice. Acta Pharmacologica et Toxicologica 35: 429 (1974).PubMedCrossRefGoogle Scholar
  2. Arita, T.; Hori, R.; Ito, K.; Ichikawa, K. and Uesugi, T.: Transformation and excretion of drugs in biological systems. II. Transformation of metoclopramide in rabbits. Chemical and Pharmaceutical Bulletin 18: 1663 (1970a).CrossRefGoogle Scholar
  3. Arita, T.; Hori, R.; Ito, K. and Ichikawa, K.: Transformation and excretion of drugs in biological systems. III. Separatory determination of metoclopramide and its N4-glucuronide and N4-sulfenate in rabbit urine and bile. Chemical and Pharmaceutical Bulletin 18: 1670 (1970b).CrossRefGoogle Scholar
  4. Arita, T.; Hori, R.; Ito, K. and Sekikawa, H.: Transformation and excretion of drugs in biological systems. IV. Reabsorption of biliary metoclopramide-N4 4-glucuronide and -N4-sulfonate from rabbit intestine. Chemical and Pharmaceutical Bulletin 18: 1675 (1970c).CrossRefGoogle Scholar
  5. Armstrong, R.F.: Metoclopramide and gastric emptying. British Journal of Anaesthesia 45: 123 (1973).PubMedCrossRefGoogle Scholar
  6. Arvanitakis, C; Gonzales, G. and Rhodes, J.B.: The role of metoclopramide in peroral jejunal biopsy —a controlled, randomised trial. Gastroenterology 68: 859 (1975).Google Scholar
  7. Assaf, R.A.E.; Clarke, R.S.J. and Dundee, J.W.: Studies of drugs given before anaesthesia. XXIV. Metoclopramide with morphine and pethidine. British Journal of Anaesthesia 46: 514 (1974a).PubMedCrossRefGoogle Scholar
  8. Assaf, R.A.E.; Dundee, J.W. and Samuel, I.O.: The efficacy of metoclopramide against narcotic-induced emetic symptoms. British Journal of Clinical Pharmacology 1: 1778 (1974b).Google Scholar
  9. Bader, E.: Metoclopramide and emergency endoscopy for upper gastro-intestinal bleeding. Lancet 1: 101 (1973).PubMedCrossRefGoogle Scholar
  10. Bakke, O.M. and Segura, J.: The absorption and elimination of metoclopramide in three animal species. Journal of Pharmacy and Pharmacology 28: 32 (1976).PubMedCrossRefGoogle Scholar
  11. Banke, L.: Research on the action of metoclopramide in the gastro-intestinal tract. In Modern Gastroenterology (Proceedings of VIII International Congress on Gastroenterology, Prague, July 1968), pp 571–572 (Schattauer, Stuttgart 1969).Google Scholar
  12. Banke, L.; Mahnstrom, J. and Heltberg, J.: The influence of metoclopramide (Primperan) and neostigmine upon early postvagotomy motor disturbances. Scandinavian Journal of Gastroenterology 7: 33 (1972).PubMedCrossRefGoogle Scholar
  13. Bar, J.: A propos d’une tentative de suicide sans consequence facheuse, avec le métoclopramide. Therapie 21: 349 (1966).PubMedGoogle Scholar
  14. Bastos, W.P.: Action of metoclopramide in arrhythmias provoked by a bensol-adrenaline association. Ciencia e Cultura 20: 389 (1968).Google Scholar
  15. Baumann, H.W.; McCallum, R.W. and Strudevant, R.A.L.: Metoclopramide. A possible antagonist of dopamine in the esophagus of man. Gastroenterology 70: 862 (1976).Google Scholar
  16. Beani, L.; Bianchi, C. and Crema, C: Effects of metoclopramide on isolated guinea-pig colon. 1) Peripheral sensitisation to acetylcholine. European Journal of Pharmacology 12: 320 (1970).PubMedCrossRefGoogle Scholar
  17. Beckett, A.H. and Huizing, G.: In vitro metabolism of metoclopramide. Journal of Pharmacy and Pharmacology 27 (Suppl.): 42P (1975).Google Scholar
  18. Behar, J. and Biancani, P.: Effect of oral metoclopramide on gastroesophageal reflux in the post-cibal state. Gastroenterology 70: 331 (1976).PubMedGoogle Scholar
  19. Bhaduri, T. and Bradley, G.W.: The effect of metoclopramide (Maxolon) on intragastric pressure and gastric motility. Clinical Trials Journal 6: 13 (1969).Google Scholar
  20. Bianchi, C; Beani, L. and Crema, C: Effects of metoclopramide on isolated guinea-pig colon. 2) Interference with ganglionic stimulant drugs. European Journal of Pharmacology 12: 332 (1970).PubMedCrossRefGoogle Scholar
  21. Birtley, R.D.N. and Baines, M.W.: The effects of metoclopramide on some isolated intestinal preparations. Postgraduate Medical Journal 49 (Suppl.4): 13 (1973).PubMedGoogle Scholar
  22. Bloch, A.: Incorrect use of metoclopramide. Harefuah 86: 411 (1974).PubMedGoogle Scholar
  23. Boissier, J.R.; Simon, P.; Lwoff, J.M. and Fichelle-Pagny, J.: Action psycholeptique du métoclopramide. Comptes Rendus des Séances de la Société de Biologie de Paris 158: 1859 (1964).Google Scholar
  24. Boisson, J. and Albot, G: Sur l’intérét thérapeutique du métoclopramide. A propos de 2,300 observations. Revue critique et indications de son emploi. Cahiers du Collège de Médecine 7: 45 (1966).Google Scholar
  25. Bolin, T.D.: The facilitation of duodenal intubation with metoclopramide. Med. J. Aust. 1: 1078 (1969).Google Scholar
  26. Bonechi, I.; Biagini, M. and Giagnoni, P.: Azione antiemetica delia Metoclopramide nell’uremia. Riforma Medica 82 (Suppl.): 1691 (1968).Google Scholar
  27. Borenstein, P. and Bles, G.: Effets cliniques et électroencéphalographiques du metoclopramide en psychiatrie. Thérapie 20: 975 (1965).PubMedGoogle Scholar
  28. Breivik, H. and Lind, B.: Anti-emetic and propulsive peristaltic properties of metoclopramide. British Journal of Anaesthesia 43: 400 (1971).PubMedCrossRefGoogle Scholar
  29. Bremner, CG. and Bremner, C.H.: Augmentation of lower oesophageal sphincter tone with metoclopramide (maxolon) in normals and in patients with sphincter incompetence. South African Journal of Surgery 10: 211 (1972).PubMedGoogle Scholar
  30. Brownlee, M. and Kroopf, S.S.: Metoclopramide for gastroparesis diabeticorum. New England Journal of Medicine 291: 1257 (1974).PubMedGoogle Scholar
  31. Buckingham, M.; Welphy, G.; Miller, J.F. and Elstein, M.: Gastro-intestinal absorption and transplacental transfer of amoxycillin during labour and the influence of metoclopramide. Current Medical Research and Opinion 3: 392 (1975).PubMedCrossRefGoogle Scholar
  32. Cannon, J.G.: Chemistry of dopaminergic agonists. Advances in Neurology 9: 177 (1975).PubMedGoogle Scholar
  33. Carnevali, G.; Roncoroni, L.; Bissanti, A. and Mainardi, L.: Action du metoclopramide sur l’evacuation gastrique. Échos de la Médecine 39: 8 (1968).Google Scholar
  34. Casteels-Van Daele, M.; Jaeken, J.; Van Der Schueren, P.; Zimmerman, A. and Van Den Bon, P.: Dystonic reactions in children caused by metoclopramide. Archives of Diseases of Children 45: 130 (1970).CrossRefGoogle Scholar
  35. Cecco, L. de; Ragni, N.; Sbernini, R.; Uleri, G. and Molinaroli, P.: Effect of metoclopramide on intestinal motility in pregnancy and the puerperium. Riforma Medica 82 (Suppl.): 1786 (1968).Google Scholar
  36. Clark, M.M. and Storrs, J.A.; The prevention of postoperative vomiting after abortion: metoclopramide. British Journal of Anaesthesia 41: 890 (1969).PubMedCrossRefGoogle Scholar
  37. Clarke, R.S.J. and Dundee, J.W.: Side-effects of antiemetics: Results of a class experiment. European Journal of Pharmacology 14: 291 (1971).PubMedCrossRefGoogle Scholar
  38. Cochlin, D.L.: Dystonic reactions due to metoclopramide and phenothiazines resembling tetanus. British Journal of Clinical Practice 28: 201 (1974).PubMedGoogle Scholar
  39. Connell, A.M. and George, J.D.: Effect of metoclopramide on gastric function in man. Gut 10: 678 (1969).PubMedCrossRefGoogle Scholar
  40. Costall, B. and Naylor, R.J.: The nucleus amygdaloideus centralis and neuroleptic activity in the rat. European Journal of Pharmacology 25: 138 (1974).PubMedCrossRefGoogle Scholar
  41. Costall, B. and Naylor, R.J.: Neuroleptic and non-neuroleptic catalepsy. Arzneimittel-Forschung 23: 674 (1973).PubMedGoogle Scholar
  42. Cousin, J.; Katende, G.; Pauli, A. and Fournier, A.: L’intoxication par le métoclopramide chez l’enfant. Journal des Sciences Médicates de Lille 91: 1 (1973).Google Scholar
  43. Davies, J.A.H. and Howells, T.H.: Management of anaesthesia for the full stomach case in the casualty department. Postgraduate Medical Journal 49 (Suppl. 4): 58 (1973).PubMedGoogle Scholar
  44. Day, M.D.: Cardiovascular dopamine receptor stimulation antagonised by metoclopramide. Journal of Pharmacy and Pharmacology 27: 276 (1975).PubMedCrossRefGoogle Scholar
  45. De Silva, K.L.; Muller, P.J. and Pearce, J.: Acute drug-induced extrapyramidal syndromes. Practitioner 211: 316 (1973).PubMedGoogle Scholar
  46. De Vries, P.M.: A double-blind crossover clinical evaluation of metoclopramide and a combination of haloperidol and isopropamide iodide in gastroenterology. Arzneimittel-Forschung 19: 1766 (1969).PubMedGoogle Scholar
  47. Dias Martins, A.: Metoclopramida nas nauseas e vomitos da gravidez. O’Hospital (Rio de Janeiro) 71: 1631 (1967).Google Scholar
  48. Dilawari, J.B. and Misiewicz, J.J.: Does oral metoclopramide increase cardiac sphincter pressure? Gut 13: 856 (1972).PubMedGoogle Scholar
  49. Diliwari, J.B. and Misiewicz, J.J.: Action of oral metoclopramide on the gastro-oesophageal junction in man. Gut 14: 380 (1973).CrossRefGoogle Scholar
  50. Dippy, J.E.; Rhodes, J. and Cross, S.: Bile reflux in gastric ulcer: The effect of smoking, metoclopramide and carbenoxolone sodium. Current Medical Research and Opinion 1: 569 (1973).PubMedCrossRefGoogle Scholar
  51. Dobkin, A.E.; Evers, W. and Israel, J.S.: Double-blind evaluation of metoclopramide (MK 745, Sinemet), trimethobenzamide (Tigan), and a placebo as postanaesthetic anti-emetics following methoxyflurane anaesthesia. Canadian Anaesthetist’s Society Journal 15: 80 (1968).CrossRefGoogle Scholar
  52. Dougan, D.F.H.; Mearrick, P.T. and Wade, D.N.: Metoclopramide as a dopamine antagonist in the heart and gut of the mollusc Tapes Watlingi Clinical and Experimental Pharmacology and Physiology 1: 473 (1974).PubMedCrossRefGoogle Scholar
  53. Douthwaite, A.H.: Hiccup. Lancet 1: 144 (1968).PubMedCrossRefGoogle Scholar
  54. Dundee, J.W. and Clarke, R.S.J.: The premedicant and anti-emetic action of metoclopramide. Postgraduate Medical Journal 49 (Suppl.4): 34 (1973).PubMedGoogle Scholar
  55. Dundee, J.W.; Clarke, R.S.J. and Howard, P.J.: Studies of drugs given before anaesthesia. XXIII. Metoclopramide. British Journal of Anaesthesia 46: 509 (1974).PubMedCrossRefGoogle Scholar
  56. Dundee, J.W.; Kirwan, M.J. and Clarke, R.S.J.: Anaesthesia and premedication as factors in postoperative vomiting. Acta Anaesthetica Scandinavica 9: 223 (1965).CrossRefGoogle Scholar
  57. Dolphin, A.; Jenner, P.; Marsden, CD.; Pycock, C. and Tarsy, D.: Pharmacological evidence for cerebral dopamine receptor blockade by metoclopramide in rodents. Psychopharmacologia 41: 133 (1975).PubMedCrossRefGoogle Scholar
  58. Editorial: Hiccup. British Medical Journal 2: 234 (1971).Google Scholar
  59. Eisner, M.: Gastro-intestinal effects of metoclopramide in man. In vitro experiments with human smooth muscle preparations. British Medical Journal 4: 679 (1968).PubMedCrossRefGoogle Scholar
  60. Eisner, M.: Effect of metoclopramide on gastro-intestinal motility in man. Digestive Diseases 16: 409 (1971).CrossRefGoogle Scholar
  61. Ellis, F.R. and Spence, A.A.: Clinical trials of metoclopramide (Maxolon) as an anti-emetic in anaesthesia. Anaesthesia 25: 368 (1970).PubMedCrossRefGoogle Scholar
  62. Fanelli, A.: The use of metoclopramide in obstetrics and gynaecology. Riforma Medica 82 (Suppl.): 1806 (1968).Google Scholar
  63. Fischer, P.A.; Schneider, E.; Jacobi, P. and Maxion, H.: Kombinationsbehandlung des Parkinson-Syndroms mit 1-Dopa und einem Decarboxylasehemmer. Medizin-ische Welt 24: 1742 (1973).Google Scholar
  64. Flavell Matts, S.G.: Metoclopramide in the treatment of migraine. Practitioner 212: 887 (1974).Google Scholar
  65. Fontaine, J. and Reuse, J.J.: Transmural stimulation of isolated guinea-pig ileum: action of metoclopramide and sulpiride. Archives Internationales de Pharmaco-dynamie et de Thérapie 197: 396 (1972).Google Scholar
  66. Fournier, A.; Pauli, A.; Ducoulombier, M. and Cousin, J.: Effets du surdosage en metoclopramide chez l’enfant. Pédiatrie 24: 799 (1969).PubMedGoogle Scholar
  67. Fritel, D.; Meyer, P.; Rey, L.P. and Grivaux, M.: Les troubles gastriques de l’insuffisance renale et leur traitement par le metoclopramide. Semaine des Hôpitaux, Therapeutique 41: 217 (1965).Google Scholar
  68. Fry, E.N.S.: Metoclopramide and drinking before general anaesthesia. Anaesthesia 29: 754 (1974).PubMedCrossRefGoogle Scholar
  69. Fry, E.N.S.: Metoclopramide and oral premedication. Anaesthesia 30: 690 (1975).PubMedCrossRefGoogle Scholar
  70. Galetti, A.; De Santis, L. and Famularo, L.: Three cases of metoclopramide poisoning (two iatrogenic and one accidental). Gaslini 6: 173 (1974).Google Scholar
  71. Galindo, F. and Mahmud, H.R.: Acción de la metoclopramida sobre la secreción pancréatica externa y el esfinter de Oddi. La Prensa Médica Argentina 59: 1615 (1972).Google Scholar
  72. Gibbons, D.O. and Lant, A.F.: Effects of intravenous and oral propantheline and metoclopramide on ethanol absorption. Clinical Pharmacology and Therapeutics 17: 578 (1975).PubMedGoogle Scholar
  73. Giger, M.: Toxische Wirkungen von Metoclopramid. Schweizerische Rundschau fur Medizin (Praxis) 64: 930 (1975).Google Scholar
  74. Glanville, J.N. and Walls, W.D.: Effect of intravenous metoclopramide on gastro-oesophagealreflux. Gut 13: 31 (1972).PubMedCrossRefGoogle Scholar
  75. Gothoni, G.; Pentikäinen, P.; Vapaatalo, H.I.; Hackman, R. and Af Björksten, K.: Absorption of antibiotics: Influence of metoclopramide and atropine on serum levels of pivampicillin and tetracycline. Annals of Clinical Research 4: 228 (1972).PubMedGoogle Scholar
  76. Guelrud, M.: Effect of intravenous metoclopramide on the incompetent lower oesophageal sphincter. American Journal of Gastroenterology 61: 119 (1974).PubMedGoogle Scholar
  77. Hackman, R.; Pentikäinen, P.; Neuvonen, P.J. and Vapaatalo, H.: Inhibition of the apomorphine gnawing compulsion by amphetamine. Experientia 34: 1524 (1973).CrossRefGoogle Scholar
  78. Hancock, B.D.; Bowen-Jones, E.; Dixon, R.; Dymock, I.W. and Cowley, DJ.: The effect of metoclopramide on gastric emptying of solid meals. Gut 15: 462 (1974).PubMedCrossRefGoogle Scholar
  79. Handley, A.J.: Metoclopramide in the prevention of postoperative nausea and vomiting. British Journal of Clinical Practice 21: 460 (1967).PubMedGoogle Scholar
  80. Harris, M.J.; Harrington, G. and Beveridge, J.: Modification to the technique for small bowel biopsy in children. American Journal of Diseases in Children 115: 43 (1968).Google Scholar
  81. Hay, A.M.: The mechanism of action of metoclopramide. Gut 16: 403 (1975).PubMedGoogle Scholar
  82. Heading, R.C.; Nimmo, J.; Prescott, L.F. and Tothill, P.: The dependence of paracetamol absorption on the rate of gastric emptying. British Journal of Pharmacology 47: 415 (1973).PubMedCrossRefGoogle Scholar
  83. Heitmann, P. and Möller, N.: The effect of metoclopramide on the gastro-oesophageal junctional zone and the distal oesophagus in man. Scandinavian Journal of Gastroenterology 5: 621 (1970).Google Scholar
  84. Herranz-Fernandez, J.L.; Monfort-Marti, A.; Moreno-Rubio, J.A. and Perez-Santos, J.L.: Efectos secundarios de la metoclopramida en pediatria. Revista Espanola de Pediatria 31: 99 (1975).Google Scholar
  85. Hoskins, E.O.L.: Metoclopramide in benign gastric ulceration. Postgrad, med. J. 49 (Suppl. 4): 95 (1973).Google Scholar
  86. Howard, F.A. and Sharp, D.S.: Effect of metoclopramide on gastric emptying during labour. British Medical Journal 1: 446 (1973).PubMedCrossRefGoogle Scholar
  87. Howarth, F.H.; Cockel, R.; Roper, B.W. and Hawkins, CF.: The effect of metoclopramide upon gastric motility and its value in barium progress meals. Clinical Radiology 20: 294 (1969).PubMedCrossRefGoogle Scholar
  88. Howells, T.H.; Khanam, T.; Kreel, L.; Seymour, C; Oliver, B. and Davies, J.A.H.: Pharmacological emptying of the stomach with metoclopramide. British Medical Journal 2: 558 (1971).PubMedCrossRefGoogle Scholar
  89. Hradsky, M. and Stockbrügger, R.: The effect of metoclopramide (Primperan) during gastroscopic observation of the antrum and pylorus. Gastrointestinal Endo-scopy 21: 55 (1974).CrossRefGoogle Scholar
  90. Hucker, H.B.; Hochberg, A.; Hoffman, E.A. and Miller, J.K.: Studies on the physiological distribution of metoclopramide. Pharmacologist 8: 220 (1966).Google Scholar
  91. Hukuhara, T.; Nakayama, S.; Fukuda, H.; Siina, H. and Neya, T.: Effects of N-(diethylamineethyl)-2-methoxy-4-amino-5-chlorobenzamide dihydrochloride (metoclopramide) upon the movements of the stomach and small intestine of dogs. Japanese Journal of Smooth Muscle Research 2: 15 (1966).CrossRefGoogle Scholar
  92. Ingrand, J. and Boulu, R.: Study of the distribution of tritiated metoclopramide in the mouse. Thérapie 25: 741 (1970).PubMedGoogle Scholar
  93. Jacoby, H.I. and Brodie, D.A.: Gastro-intestinal actions of metoclopramide. An experimental study. Gastroenterology 52: 676 (1967).Google Scholar
  94. James, W.B. and Hume, R.: Action of metoclopramide on gastric emptying and small bowel transit time. Gut 9: 203 (1968).PubMedCrossRefGoogle Scholar
  95. James, W.B. and Melrose, A.G.: Metoclopramide in gastrointestinal radiology. Clinical Radiology 20: 57 (1969).PubMedCrossRefGoogle Scholar
  96. Janssen, P.A.J.; Niemegeers, C.J.E.; Schellekens, K.H.L. and Lenaerts, F.M.: Is it possible to predict the clinical effects of neuroleptic drugs (major tranquillisers) from animal data? Arzneimittel-Forschung 17: 841 (1967).PubMedGoogle Scholar
  97. Johnson, A.G.: The action of metoclopramide on the canine stomach, duodenum, and gall-bladder. British Journal of Surgery 56: 696 (1969).PubMedCrossRefGoogle Scholar
  98. Johnson, A.G.: The effect of metoclopramide on gastro-duodenal and gallbladder contractions. Gut 12: 158 (1971a).PubMedCrossRefGoogle Scholar
  99. Johnson, A.G.: The action of metoclopramide on human gastroduodenal motility. Gut 12: 421 (1971b).PubMedCrossRefGoogle Scholar
  100. Johnson, A.G.: Controlled trial of metoclopramide in the treatment of flatulent dyspepsia. British Medical Journal 2: 25 (1971c).PubMedCrossRefGoogle Scholar
  101. Johnson, A.G.: Gastroduodenal motility and synchronisation. Postgraduate Medical Journal 49 (Suppl.4): 29 (1973a).PubMedGoogle Scholar
  102. Johnson, A.G.: Flatulent dyspepsia. Postgraduate Medical Journal 49 (Suppl.4): 104 (1973b).PubMedGoogle Scholar
  103. Jones, C.T.: Metoclopramide in the treatment of nausea. A double-blind trial. New Zealand Medical Journal 68: 388 (1968).Google Scholar
  104. Justin-Besancon, L. and Laville, C: Action antiémétique du métoclopramide vis-á-vis de l’apomorphine et de l’hydergine. Comptes Rendus des Séances de la Société de Biologie de Paris 158: 723 (1964a).Google Scholar
  105. Justin-Besancon, L. and Laville, C: Action du métoclopramide sur le systeme nerveux autonome. Comptes Rendus des Séances de la Société de Biologie de Paris 158: 1016 (1964b).Google Scholar
  106. Katevuo, K.; Kanto, J. and Pihlajamaki, K.: The effect of metoclopramide on the contraction of the human gallbladder. Investigative Radiology 10: 197 (1975).PubMedCrossRefGoogle Scholar
  107. Kelly, J.M.: Metoclopramide in the vagotomised stomach. Part II —In dog. Postgraduate Medical Journal 49 (Suppl.4): 83 (1973).PubMedGoogle Scholar
  108. Kennedy, T.: Metoclopramide in the vagotomised stomach. Part I —In man. Postgraduate Medical Journal 49 (Suppl.4): 81 (1973a).PubMedGoogle Scholar
  109. Kennedy, T.: In discussion. Postgraduate Medical Journal 49 (Suppl.4): 98 (1973b).Google Scholar
  110. Klein, R.L.; Militello, T.E. and Ballinger, C.M.: Antiemetic effect of metoclopramide... Evaluation in humans. Anaesthesia and Analgesia 47: 259 (1968).Google Scholar
  111. Kocian, J. and Kocianova, J.: Klinische Erfahrungen mit Paspertin in der Gastroenterologie. Medizinische Welt 26: 1939 (1975).PubMedGoogle Scholar
  112. Korczyn, A.D.: Hiccup. British Medical Journal 2: 590 (1971).PubMedCrossRefGoogle Scholar
  113. Kreel, L.: The use of oral metoclopramide in the barium meal and follow-through examination. British Journal of Radiology 43: 31 (1970).PubMedCrossRefGoogle Scholar
  114. Kreel, L.: The use of metoclopramide in radiology. Postgraduate Medical Journal 49 (Suppl. 4): 42 (1973).PubMedGoogle Scholar
  115. Kreel, L.; Trott, M. and Howells, T.H.: The influence of oral metoclopramide on gastric emptying after a fixed water load. Clinical Radiology 23: 213 (1972).PubMedCrossRefGoogle Scholar
  116. Kumada, S.: Details on the discovery of Primperan, its security and destiny in a living body. First Symposium on Therapy with New Drugs, Nagoya, 1965, pp. 23–26.Google Scholar
  117. La Barre, J.: A propos du mode d’action du métoclopramide en thérapeutique gastro-intestinale. Pathologie et Biologie 17: 663 (1969).PubMedGoogle Scholar
  118. Laville, C: Protection exercée par le métoclopramide contre les effets vomitifs du sulfate de cuivre. Pathologie et Biologie 12: 577 (1964).PubMedGoogle Scholar
  119. Lind, B. and Breivik, H.: Metoclopramide and perphenazine in the prevention of postoperative nausea and vomiting. A double-blind comparison. British Journal of Anaesthesia 42: 614 (1970).Google Scholar
  120. McCallum, R.; Ippoliti, A.; Cooney, C and Sturdevant, R.A.L.: A double-blind trial of metoclopranide in symptomatic gastro-oesophageal reflux. Gastroenterology 70: 962 (1976).Google Scholar
  121. McCallum, R.W.; Kline, M.M.; Curry, N. and Sturdevant, R.A.L.: Comparative effects of metoclopramide and bethanechol on lower oesophageal sphincter pressure in reflux patients. Gastroenterology 68: 1114 (1975).PubMedGoogle Scholar
  122. McGarry, J.M.: A double-blind comparison of the antiemetic effect during labour of metoclopramide and perphenazine. British Journal of Anaesthesia 43: 613 (1971).PubMedCrossRefGoogle Scholar
  123. McMurray, G.N.: An evaluation of metoclopramide as an anti-emetic in seasickness. Postgraduate Medical Journal 49 (Suppl.4): 38 (1973).PubMedGoogle Scholar
  124. McNeilly, A.S.; Thomer, M.O.; Volans, G. and Besser, G.M.: Metoclopramide and prolactin. British Medical Journal 2: 729 (1974).PubMedCrossRefGoogle Scholar
  125. Madanagopolan, N.: Metoclopramide in hiccup. Current Medical Research and Opinion 3: 371 (1975).PubMedCrossRefGoogle Scholar
  126. Malméjac J. and Laville, C: Effets cardiovasculaires du métoclopramide. Pathologie et Biologie 12: 1074 (1964).PubMedGoogle Scholar
  127. Manninen, V.; Apajalahti, A.; Melin, J. and Karesoja, M.: Altered absorption of digoxin in patients given propantheline and metoclopramide. Lancet 1: 398 (1973a).PubMedCrossRefGoogle Scholar
  128. Manninen, V.; Apajalahti, A.; Simonen, H. and Reissei, P.: Effect of propantheline and metoclopramide on absorption of digoxin. Lancet 1: 1118 (1973b).PubMedCrossRefGoogle Scholar
  129. Margieson, G.R.; Sorby, A. and Williams, H.B.L.: The action of metoclopramide on gastric emptying: A radiological assessment. Medical Journal of Australia 2: 1272 (1966).PubMedGoogle Scholar
  130. Margieson, G.R. and Williams, H.B.L.: Radiopharmacology of the stomach with special reference to the effects of metoclopramide. Australian Radiology 12: 239 (1968).CrossRefGoogle Scholar
  131. Marino, A.; Girone, E.; Battista, O. and De Marino, V.: Effetti della metoclopramide sul comportamento spontaneo e condiazionato, sulla convulsivita da cardiazolo e sull’elettrocardiogramma. Antologia di Medicina e Igiene 6: 1173 (1968).Google Scholar
  132. Marmo, E.; Di Giacomo, S. and Imperatore, A.: Metoclopramid und electrokardiographische Veranderungen-durch KCl, BaCl2, CaCl2, MgCl2, Aconitin, k-Strophanthosid, Vasopressin und durch Asphyxie. Arzneimittel-Forschung 20: 12 (1970a).PubMedGoogle Scholar
  133. Marmo, E.; Di Mezza, F.; Imperatore, A. and Di Giacomo, S.: Metoclopramid und die Muskulatur von Ösophagus, Magen, Darm, Milz, Trachea, Gallen- und Harnblase: Untersuchungen in vitro. Arzneimittel-Forschung 20: 18 (1970b).Google Scholar
  134. Marmo, E.; Imperatore, A. and di Giacomo, S.: Effects of metoclopramide on the cardiovascular apparatus and on the relative autonomic nervous system. La Clinica Terapeutica 51: 509 (1969).PubMedGoogle Scholar
  135. Marshall, N.W.: A double-blind trial of metoclopramide and prochlorperazine in general practice. British Journal of Clinical Practice 24: 25 (1970).PubMedGoogle Scholar
  136. Martin, P.D. and Scobie, B.A.: Metoclopramide and gastric emptying. New Zealand Medical Journal 67: 494 (1967).Google Scholar
  137. Matuchansky, C; Huet, P.M.; Mary, J.Y.; Rambaud, J.C. and Bernier, J.J.: Effects of cholecystokinin and metoclopramide on jejunal movements of water and electrolytes and on the transit time of luminal fluid in man. European Journal of Clinical Investigation 2: 169 (1972).CrossRefGoogle Scholar
  138. Mearrick, P.T.; Wade, D.N.; Birkett, D.J. and Morris, J.: Metoclopramide, gastric emptying and l-dopa absorption. Australian and New Zealand Journal of Medicine 4: 144 (1974).PubMedCrossRefGoogle Scholar
  139. Medin, S. and Nyberg, L.: Effect of propantheline and metoclopramide on absorption of digoxin. Lancet 1: 1393 (1973).PubMedCrossRefGoogle Scholar
  140. Meeroff, J.C.: The effect of metoclopramide on human gastric emptying and secretion. Acta Gastroenterologica Latin America 6: 55 (1974).Google Scholar
  141. Middleton, R.S.W.: The use of metoclopramide in the elderly. Postgraduate Medical Journal 49 (Suppl. 4): 90 (1973).PubMedGoogle Scholar
  142. Metzger, W.; Cano, R. and Sturdevant, R.A.L.: Effect of metoclopramide in chronic gastric retention after gastric surgery. Gastroenterology 68: 954 (1975).Google Scholar
  143. Mitchell, A.B.S. and Parkins, R.A.: Metoclopramide as an adjunct to small bowel intubation. Gut 10: 690 (1969).PubMedCrossRefGoogle Scholar
  144. Miyake, T.; Yamamoto, Y.; Ariyoshi, J.; Suzaki, T.; Hajiro, K.; Todo, A.; Ohishi, M.; Hoshino, T. and Yanagihara, K.: Clinical evaluation of metoclopramide (Primperan) —a double-blind controlled trial. Japanese Archives of Internal Medicine 19: 249 (1972).Google Scholar
  145. Modica, G.; Sorrentino, F.; Gulisano, G. and Bortoli, M.G.de.: Effects of metoclopramide on the motility of the biliary ducts. Riforma Medica 84: 817 (1970).Google Scholar
  146. Moertel, CG. and Reitemeier, R.J.: Controlled clinical studies of orally administered antiemetic drugs. Gastroenterology 57: 262 (1969).PubMedGoogle Scholar
  147. Moshal, M.G.: The propulsive action of metoclopramide (Maxolon). South African Medical Journal 46: 1871 (1972).PubMedGoogle Scholar
  148. Moshal, M.G.: Trials with metoclopramide in duodenal ulceration. Postgraduate Medical Journal 49 (Suppl. 4): 100 (1973).PubMedGoogle Scholar
  149. Muller, J.M.; Denis, B.; Schaerer, R. and Cordonnier, D.: Utilisation clinique du Métoclopramide dans le traitement des nausées, des vomissements et du hoquet des insuffisants renaux chroniques. Grenoble Medico-Chirurgical 6: 73 (1968).Google Scholar
  150. Mur Linares, J. and Llorca, V.: La metoclopramide en el ulcus gastroduodenal. Cinco anos de observacion clinico-biologico-radiologica. Medizinishce Klinik (Edicion en Espanol) 8: 38 (1968).Google Scholar
  151. Nakra, B.R.S.; Bond, A.J. and Lader, M.H.: Comparative psychotropic effects of metoclopramide and prochlorperazine in normal subjects. Journal of Clinical Pharmacology 15: 449 (1975).PubMedGoogle Scholar
  152. Natale, L.: Trattamento di alcuni disturbi funzionali dell’apparato digerente: sperimentazione clinica di confronto fra un preparato d’associazione di medazepam e metoclopramide ed uno d’associazione di medazepam con un anticolinergico. La Clinica Terapeutica 72: 141 (1975).PubMedGoogle Scholar
  153. Nimmo, J.: The influence of metoclopramide on drug absorption. Postgraduate Medical Journal 49 (Suppl. 4): 25 (1973).PubMedGoogle Scholar
  154. Nimmo, J.; Heading, R.C.; Tothill, P. and Prescott, L.F.: Pharmacological modification of gastric emptying: Effects of propantheline and metoclopramide on paracetamol absorption. British Medical Journal 1: 587 (1973).PubMedCrossRefGoogle Scholar
  155. Öigaard, A.: The motor-stimulating effect of metoclopramide and pyridostigmine bromide in normal man and laparotomised patients. Scandinavian Journal of Gastroenterology 10: 65 (1975).PubMedGoogle Scholar
  156. Pagnini, G. and Di Carlo, R.: Investigations on the interaction of 2-methoxy-5-chloroprocainamide (metoclopramide) with serum proteins. Arzneimittel-Forschung 22: 780 (1972).PubMedGoogle Scholar
  157. Pauli, A. and Kerr Grant, A.: A controlled trial of meto-clopramide in reflux oesophagitis. Medical Journal of Australia 2: 627 (1974).Google Scholar
  158. Pearson, M.C.; Edwards, D.; Tate, A.; Gilkes, R.; Saxton, H.M. and Rowland, C: Comparison of the effects of oral and intravenous metoclopramide on the small bowel. Postgraduate Medical Journal 49 (Suppl. 4): 47 (1973).PubMedGoogle Scholar
  159. Peringer, E.; Jenner, P. and Marsden, CD.: Effect of metoclopramide on turnover of brain dopamine, noradrenaline and 5-hydroxytryptamine. Journal of Pharmacy and Pharmacology 27: 442 (1975).PubMedCrossRefGoogle Scholar
  160. Pirola, R.C.: Rapid duodenal intubation with metoclopramide. American Journal of Digestive Diseases 12: 913 (1967).PubMedCrossRefGoogle Scholar
  161. Poignant, J.C.; Laubie, M.; Tsoucaris-Kupfer, D. and Schmitt, H.M.: The effect of various pharmacological agents on the stereotyped movements produced in the rat by injection of l-(2″-pyrimidyl)-4-piperonylpiperazine (piribedil). Comptes Rendus Hebdomadaires des seances de l’Academie des Sciences, Paris, Series D 275: 715 (1972).Google Scholar
  162. Ramos, A.O.; Bastos, W.P. and Sakata, M.: Influence of metoclopramide in experimental arrhythmias induced by barium or by chloroform and adrenaline. Medecina et Pharmacologia Experimentalis 17: 385 (1967).Google Scholar
  163. Ramsbottom, N. and Hunt, J.N.: Studies of the effect of metoclopramide and apomorphine on gastric emptying and secretion in man. Gut 11: 989 (1970).PubMedCrossRefGoogle Scholar
  164. Rentzhog, L. and Wikstrom, S.: Pharmacological effects of gastric emptying following laparotomy in the rat. Acta Chirurgica Scandinavic 141: 649 (1975).Google Scholar
  165. Robinson, O.P.W.: Metoclopramide —a new pharmacological approach? Postgraduate Medical Journal 49 (Suppl. 4): 77 (1973b).PubMedGoogle Scholar
  166. Salas, J.R.: Metoclopramide for vertigo. New Zealand Medical Journal 66: 870 (1967).PubMedGoogle Scholar
  167. Savio, E. and Pontiggia, P.: Metoclopramide e assorbimento intestinale di isoniazide. Annali di Medicina Sondalol 3: 402 (1965).Google Scholar
  168. Scalabrino, R. and Pasquariello, G.: Effeti indesideriabili da farmaci. Esperienze con metoclopramide. Riforma Medica 82 (Suppl.): 1562 (1968).Google Scholar
  169. Scarzella, R.; Gario, S. and Ferrari, G.: Nota preliminare sull’azione di alte dosi di metoclopramide nell’uomo. Riforma Medica 82 (Suppl.): 2010 (1968).Google Scholar
  170. Schmid, E. and Ritter, U.: Enfluss von rektal appliziertem Hyoscin-N-butylbromide auf die Dündarnmotilitat. Arzneimittel-Forschung 22: 2149 (1972).PubMedGoogle Scholar
  171. Schütz, E.: Fortschritte in der Therapie des Ulcus duodeni. de Verkürzte Heildauer unter hohen Gaben von Paspertin. Münchener Medizinische Wochenshrift 118: 231 (1976).Google Scholar
  172. Sethobhakdi, S.; Sricharoen, V. and Wilairatana, S.: The effect of metoclopramide on gastric emptying. American Journal of Proctology 26: 51 (1975).Google Scholar
  173. Shah, Z.P. and Wilson, J.: An evaluation of metoclopramide (Maxolon) as an anti-emetic in minor gynaecological surgery. British Journal of Anaesthesia 44: 865 (1972).PubMedCrossRefGoogle Scholar
  174. Shaklai, M.; Pinkhas, J. and De Vries, A.: Metoclopramide and cardiac arrhythmia. British Medical Journal 2: 385 (1974).PubMedCrossRefGoogle Scholar
  175. Sicard, J.-P.; Reignier, A. and Bakouche, P. Manifestations extrapyramidales dues au métoclopramide. A propos de 6 observations. La Nouvelle Presse Médicale 2: 31 (1973).Google Scholar
  176. Singh, M.S. and Lean, T.H.: The use of metoclopramide (Maxolon) in hyperemesis gravidarum. Proceedings of the Obstetrical and Gynaecological Society, Singapore 1: 43 (1970).Google Scholar
  177. Sousa, P.L.R.: Metoclopramide and breast-feeding. British Medical Journal 1: 512 (1975).PubMedCrossRefGoogle Scholar
  178. Stadaas, J. and Aune, S.: The effect of metoclopramide (Primperan) on gastric motility before and after vagotomy in man. Scandinavian Journal of Gastroenterology 6: 17 (1971).PubMedCrossRefGoogle Scholar
  179. Stadaas, J.O. and Aune, S.: Clinical trial of metoclopramide in postvagotomy gastric stasis. Archives of Surgery 104: 684 (1972).PubMedCrossRefGoogle Scholar
  180. Stanciu, C. and Bennett, J.R.: Metoclopramide in gastro-oesophageal reflux. Gut 14: 275 (1973).PubMedCrossRefGoogle Scholar
  181. Stewart, I.A. and Maran, A.G.D.: The effects of metoclopramide on nystagmus and vertigo. Postgraudate Medical Journal 49 (Suppl. 4): 19 (1973).Google Scholar
  182. Takaori, S.; Nakai, Y.; Matsuoka, I.; Sasa, M.; Fukuda, N. and Shimamoto, K.: The mechanism of antagonism between apomorphine and metoclopramide on unit discharges from nuclear structures in the brainstem of the cat. International Journal of Neuropharmacology 7: 115 (1968).PubMedCrossRefGoogle Scholar
  183. Takaori, S.; Nakai, Y.; Matsuoka, I.; Sasa, M. and Shimamoto, K.: Pharmacological action of N-(Diethylaminoethyl)-2-methoxy-4-amino-5-chloro-benzamide dihydrochloride. Current Clinics 1: 158 (1967).Google Scholar
  184. Tarpila, S. and Wiljasalo, M.: Metoclopramide accelerating the introduction of an intraduodenal tube. Annales Medecinae Internae Fenniae. 55: 75 (1966).Google Scholar
  185. Tarsy, D.; Parkes, J.D. and Marsden, CD.: Metoclopramide and pimozide in Parkinson’s disease and levodopa-induced dyskinesias. Journal of Neurology, Neurosurgery, and Psychiatry 38: 331 (1975).PubMedCrossRefGoogle Scholar
  186. Thompson, W.G.: Altered absorption of digoxin in patients given propantheline and metoclopramide. Lancet 1: 783 (1973).PubMedCrossRefGoogle Scholar
  187. Thorburn, C.W. and Sowton, E.: The haemodynamic effects of metoclopramide. Postgraduate Medical Journal 49 (Suppl. 4): 22 (1973).PubMedGoogle Scholar
  188. Tinker, J. and Cox, A.G.: Effect of metoclopramide on transport in the small intestine of the dog. Gut 10: 986 (1969).PubMedCrossRefGoogle Scholar
  189. Tornetta, F.J.: Clinical studies with the new antiemetic, metoclopramide. Anesthesia and Analgesia 48: 198 (1969).PubMedGoogle Scholar
  190. Trafford, J.A.P.; Fisher, A.M.H.: Marshall, S. and Douth-waite, A.H.: Metoclopramide (Maxolon) —A new anti-emetic. British Journal of Clinical Practice 21: 457 (1967).PubMedGoogle Scholar
  191. Uzeta Mejia, S.: Estudio doble ciego con metoclopramida y placebo en diversos trastomos dispepticos. Revista Faculdad Medica 14: 367 (1971).Google Scholar
  192. Valenzuela, J.E.; Defilippi, C. and Csendes, A.: Manometric studies on the human pyloric sphincter. Effect of cigarette smoking, metoclopramide, and atropine. Gastroenterology 70: 481 (1976).Google Scholar
  193. Venables, C.W.; Bell, D. and Eccleston, D.: A double-blind study of metoclopramide in symptomatic peptic oesophagitis. Postgraduate Medical Journal 49 (Suppl. 4): 73 (1973).PubMedGoogle Scholar
  194. Vialatte, J. and Paupe, J.: Applications du métoclopramide aux vomissements du nourisson et de l’enfant. Semaine des Hôpitaux de Paris 40: 2367 (1964).PubMedGoogle Scholar
  195. Volans, G.N.: The effect of metoclopramide on the absorption of effervescent aspirin in migraine. British Journal of Clinical Pharmacology 2: 57 (1975).PubMedGoogle Scholar
  196. Ward, H.W.C.: Metoclopramide and prochlorperazine in radiation sickness. British Medical Journal 2: 52 (1973).PubMedCrossRefGoogle Scholar
  197. Ward, H.W.C.: Metoclopramide and prolactin. British Medical Journal 3: 169 (1974).PubMedCrossRefGoogle Scholar
  198. Watanabe, N.; Nakai, T.; Iwanami, K. and Fujii, T.: Studies on the subchronic and chronic toxicity of metoclopramide. Yakugaku Kenkyu (Japanese Journal of Pharmaceutical Chemistry) 39: 75 (1968a).Google Scholar
  199. Watanabe, N.; Iwanami, K. and Nakahara, N.: Teratogenicity of metoclopramide Yakugaku Kenkyu (Japanese Journal of Pharmaceutical Chemistry) 39: 92 (1968b).Google Scholar
  200. Weisbrodt, N.W.; Wiley, J.N.; Overholt, CF. and Bass, P.: A relation between gastroduodenal muscle contractions and gastric emptying. Gut 10: 543 (1969).PubMedCrossRefGoogle Scholar
  201. Zer, M. and Dintsman, M.: The use of metoclopramide in acute pyloric obstruction. American Journal of Gastroenterology 63: 232 (1975).PubMedGoogle Scholar

Copyright information

© ADIS Press 1976

Authors and Affiliations

  • R. M. Pinder
    • 1
  • R. N. Brogden
    • 1
  • Phyllis R. Sawyer
    • 1
  • T. M. Speight
    • 1
  • G. S. Avery
    • 1
  1. 1.Australasian Drug Information ServicesBikenhead, Auckland 10New Zealand

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