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Metoclopramide also acts at serotonin receptors.

I was pleased to read the article by Fujii and Uemura (1), which explored one of the less well known properties of metoclopramide, that of pain minimisation with propofol injection. The drug has a number of other useful effects, some of which were discussed in the text. The reference to dopaminergic blockade as the main mechanism of action for these other effects however is inaccurate. Since the paper by Albibi and McCallum (2), a body of evidence has accumulated which indicates that much of the therapeutic effect is due to serotonin (5HT) receptor modulation, whilst dopamine antagonism causes most of the side-effects (3-5). Metoclopramide's peripheral action to increase lower oesophageal sphincter tone and gastric emptying occurs via 5HT4 receptor stimulation (3,4), whilst the central antiemetic effect may be attributed to 5HT3 receptor blockade (3-5). Although the drug is less potent than the newer highly selective 5HT3 blocking agents at the 5HT3 receptor (3,5), peak levels achieved after intravenous injection are probably sufficient for a short therapeutic period of centrally mediated antiemesis. Metoclopramide has been shown to have a lasting antiemetic effect in some chemotherapy regimensat adult doses from 1 to 4 mg/kg, however at these levels dopaminergic side-effects are more likely (5). This data may be reconciled with the systematic review findings that during the first six or 48 hours postoperatively, metoclopramide at lower doses is no better than placebo at preventing nausea and vomiting (4).


Adelaide, South Australia


(1.) Fujii Y, Uemura A. Effect of metoclopramide on pain on injection of propofol. Anaesth Intensive Care 2004; 32:653-656.

(2.) Albibi R, McCallum R. Metoclopramide: Pharmacology and clinical application. Ann Intern Med 1983; 98:86-95.

(3.) Murphy EJ. A Reappraisal of Metoclopramide. In: Keneally J, Jones M, eds. Australasian Anaesthesia 2003. Australian and New Zealand College of Anaesthetists, Melbourne, Victoria 2003; 79-88.

(4.) Henzi I, Walder B, Tramer MR. Metoclopramide in the prevention of postoperative nausea and vomiting: a quantitative systematic review of randomized, placebo-controlled studies. Br J Anaesth 1999; 83:761-771.

(5.) Tyers MB. Pharmacology and preclinical anti-emetic properties of ondansetron. Semin Oncol 1992; 19(4 Suppl 10):1-8.
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Title Annotation:Correspondence
Author:Murphy, E.
Publication:Anaesthesia and Intensive Care
Article Type:Letter to the editor
Date:Jun 1, 2007
Previous Article:Yearbook of Intensive Care and Emergency Medicine 2007.
Next Article:The Worst of Evils: The Fight Against Pain.

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