Review article: metoclopramide and tardive dyskinesia.
BACKGROUND
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.


OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
Community prevalence and pharmacogenetic mechanisms involved in metoclopramide-induced tardive dyskinesia require further study to define the benefit-risk ratio more clearly.
Rao
A S
AS
Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), College of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Camilleri
M
M
D018492:Dopamine Antagonists / Q000009:adverse effects / Q000493:pharmacokinetics*; D004409:Dyskinesia, Drug-Induced / Q000209:etiology*; D006801:Humans; D008787:Metoclopramide / Q000009:adverse effects / Q000493:pharmacokinetics*; D016017:Odds Ratio; D015995:Prevalence; D012307:Risk Factors
D018492:Dopamine Antagonists; D008787:Metoclopramide