Background Metoclopramide is primarily a dopamine receptor antagonist, with 5HT3 receptor antagonist and 5HT4 receptor agonist activity, and used as an antiemetic and gastroprokinetic since almost 50 years. Regulatory authorities issued restrictions and recommendations regarding long‐term use of the drug at oral doses exceeding 10 mg 3‐4 times daily because of the risk for development of tardive dyskinesia. The aim of our study was to review mechanism(s) of action and pharmacokinetic‐pharmacodynamic properties of metoclopramide, as well as the risk of metoclopramide‐induced tardive dyskinesia, factors that may change drug exposure in humans, and to summarize the clinical context for appropriate use of the drug. Methods A PubMed, Google Scholar, and Cross Reference search was done using the key words and combined searches: drug‐drug interaction, gastroparesis, metoclopramide, natural history, pharmacokinetics, pharmacodynamics, drug‐drug interaction, outcome, risk factors, tardive dyskinesia. Key results Data show that the risk of tardive dyskinesia from metoclopramide is low, in the range of 0.1% per 1000 patient years. This is far below a previously estimated 1%‐10% risk suggested in treatment guidelines by regulatory authorities. High‐risk groups are elderly females, diabetics, patients with liver or kidney failure, and patients with concomitant antipsychotic drug therapy, which reduces the threshold for neurological complications. Conclusions & Inferences The risk of tardive dyskinesia due to metoclopramide is far below approximated numbers in treatment guidelines. This risk and the influence of known risk factors should be considered when starting a course of metoclopramide for treatment of gastroparesis.

The effect of peptide YY (PYY) on the myoelectric activity of the small intestine was studied in relation to the transit of a 51Cr marker solution in fasted conscious rats. The myoelectric activity was recorded by means of bipolar electrodes implanted at 5, 20, and 35 cm from the pylorus. The marker was administered in the duodenum immediately after an activity front of a migrating myoelectric complex (MMC) had passed the first recording site. Under control conditions, the propagation of one activity front over the three recording levels was accompanied by the propulsion of 90.2 +/- 11.4% of the total radioactivity as one portion distal to the third electrode site. The median peak of the radioactivity was recovered at a distance approximately twice that propagated by an activity front. Intravenous infusion of PYY (50 pmol X kg-1 X min-1) had no effect on the occurrence of the MMC in the duodenum but interrupted its distal propagation and almost totally abolished the spiking activity in the jejunum. In comparison with controls, the transport of the marker was significantly retarded, and the median peak of the radioactivity was recovered proximal to the third electrode site. The results indicate that the small-intestinal contents are propelled as one portion in front of a propagating activity front. The inhibition of the activity front by PYY may account for the delay in the transit of the small-intestinal contents.(ABSTRACT TRUNCATED AT 250 WORDS)

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