Metoclopramide in Gastroparesis: Its Mechanism of Action and Safety Profile

Metoclopramide has been the cornerstone of gastroparesis management for the past 40 years as it is the only FDA-approved medication for gastroparesis. Other medications such as erythromycin and domperidone have been used off-label with variable efficacy. Historically, metoclopramide has been used in oral, intravenous, and subcutaneous formulations. It is an antiemetic and prokinetic medication that acts through the inhibition of central (chemoreceptor trigger zone) and peripheral dopaminergic and serotogenic receptors. Due to its antidopaminergic effects, extrapyramidal symptoms have been reported, with the most feared adverse event being tardive dyskinesia. Subsequently, the FDA issued a metoclopramide black box warning label in February 2009 due to its risk of causing tardive dyskinesia, which can be irreversible. The incidence and prevalence of tardive dyskinesia among metoclopramide users have been variable in different studies. However, upon review of the current literature, the true prevalence of tardive dyskinesia seems to be lower than previously thought. This review will focus on metoclopramide and the extrapyramidal symptoms associated with its use.