Review article: metoclopramide and tardive dyskinesia
- 2 December 2009
- journal article
- review article
- Published by Wiley in Alimentary Pharmacology & Therapeutics
- Vol. 31 (1), 11-19
- https://doi.org/10.1111/j.1365-2036.2009.04189.x
Abstract
Metoclopramide is a dopamine receptor antagonist which has been used for treatment of a variety of gastrointestinal symptoms over the last thirty years. In 2009, the FDA issued a black box warning regarding long-term or high-dose use of this medication because of the risk of developing tardive dyskinesia. To review the mechanism of action and pharmacokinetic properties of metoclopramide, the risk of metoclopramide-induced tardive dyskinesia, potential mechanisms that may alter and to summarize the clinical context for appropriate use of the drug. We conducted a PubMed search using the following key words and combined searches: metoclopramide, neuroleptics, tardive dyskinesia, incidence, prevalence, dopamine, receptors, pharmacokinetic, pharmacology, pharmacogenetics, DRD3 Ser9Gly polymorphism, cytochrome P450, p-glycoprotein, risk factors, gastroparesis, outcome, natural history. Available data show that risk of tardive dyskinesia from metoclopramide use is likely to be <1%, much less than the estimated 1-10% risk previously suggested in national guidelines. Tardive dyskinesia may represent an idiosyncratic response to metoclopramide; pharmacogenetics affect pharmacokinetic and dopamine receptor pharmacodynamics in response to neuroleptic agents that cause similar neurological complications. Community prevalence and pharmacogenetic mechanisms involved in metoclopramide-induced tardive dyskinesia require further study to define the benefit-risk ratio more clearly.Keywords
This publication has 38 references indexed in Scilit:
- Managing Drug-Risk Information — What to Do with All Those New NumbersNew England Journal of Medicine, 2009
- The Incidence, Prevalence, and Outcomes of Patients With Gastroparesis in Olmsted County, Minnesota, From 1996 to 2006Gastroenterology, 2009
- Metoclopramide, an Increasingly Recognized Cause of Tardive DyskinesiaThe Journal of Clinical Pharmacology, 2008
- Evidence of lowest brain penetration of an antiemetic drug, metopimazine, compared to domperidone, metoclopramide and chlorpromazine, using an in vitro model of the blood–brain barrierPharmacological Research, 2007
- Clinical implications of enteric and central D2 receptor blockade by antidopaminergic gastrointestinal prokineticsAlimentary Pharmacology & Therapeutics, 2004
- The broad‐spectrum anti‐emetic activity of AS‐8112, a novel dopamine D2, D3 and 5‐HT3 receptors antagonistBritish Journal of Pharmacology, 2001
- Proposed Schizophrenia-Related Gene Polymorphism: Expression of the Ser9Gly Mutant Human Dopamine D3Receptor with the Semliki Forest Virus SystemBiochemical and Biophysical Research Communications, 1996
- Peripheral receptor populations involved in the regulation of gastrointestinal motility and the pharmacological actions of metoclopramide-like drugsLife Sciences, 1985
- Tardive dyskinesia associated with metoclopramide.BMJ, 1984
- Clinical Pharmacokinetics of MetoclopramideClinical Pharmacokinetics, 1983