Metoclopramide Increases Vasopressin Secretion

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Abstract
The possibility that metoclopramide (MCP), a potent stimulator of aldosterone secretion, might influence vasopressin secretion in man was studied. MCP (10 mg, iv) increased plasma vasopressin (mean ± SD) from 1.3 ± 0.1 to 2.4 ± 0.1 pg⁄ml at 10 min and to 2.65± 0.1 pg⁄ml at 20 min (P < 0.01) in 10 recumbent normal subjects. No changes in plasma osmolality or peripheral hemodynamics, which might have accounted for the increase in vasopressin, were found. Sulpiride (100 mg iv), haloperidol (2 mg, iv), and domperidone (20 mg, iv), three chemically unrelated antidopaminergic agents, as well as TRH (200 μg, iv), failed to modify plasma vasopressin, thus suggesting that the MCP effect on vasopressin is not linked to its antidopaminergic and⁄or PRL-releasing properties. MCP also was effective in releasing vasopressin in 5 dehydrated subjects, in whom plasma vasopressin increased from 1.9 ± 0.2 to 3.1 ± 4 pg⁄ml (P < 0.05), and in 5 subjects during steady state water diuresis, in whom free water excretion decreased from 9 to 1 ml⁄min (P < 0.01) and plasma vasopressin increased from 0.3 ± 0.1 to 1.2 ± 0.2 pg⁄ml (P < 0.05). No changes in either vasopressin secretion or free water excretion occurred in 4 patients with severe central diabetes insipidus. These results suggest that MCP stimulates the release of biologically active vasopressin in man.