Increased prolactin and thyrotrophin secretion following oral metoclopramide: dose-response relationships

Four normal men received 1, 5, 10 and 20 mg doses of oral metoclopramide, a dopamine receptor antagonist, or placebo to determine the effect of this drug on anterior pituitary hormone secretion. Increases in serum prolactin (PRL) occurred even after the 1 mg tablet (P less than 0.01) while maximal responses were observed 60 min after ingestion of the 20 mg tablet (mean 27.8 ng/ml; range 25.6-30.3 ng/ml). Serum PRL levels peaked 60-90 min after ingestion of any dose of metoclopramide and values remained significantly elevated (P less than 0.05) for up to 8h after the tablet. Increases in serum thyrotrophin (TSH) also occurred after the 10 and 20 mg doses of metoclopramide. Peak responses were seen at 120-180 min, with significant elevation (P less than 0.05) persisting from 60 to 240 min after ingestion. No consistent changes in serum FSH, LH or GH were observed and no side-effects were reported. It was concluded that metoclopramide elevated serum PRL and TSH. The threshold dose of metoclopramide required for these effects was different for the two hormones; their peak responses occurred at different times and the duration of the elevation was dissimilar, suggesting a mechanism other than the release of hypothalamic thyrotrophin-releasing hormone (TRH).