Effects of metoclopramide and tropisetron on aldosterone secretion possibly due to agonism and antagonism at the 5-HT4 receptor

Objective: Part of the prokinetic activity of metoclopramide can possibly be ascribed to agonist activity at 5-HT4 receptors. The 5-HT3 antagonist tropisetron is thought to act as an antagonist at 5-HT4 receptors. In the present study aldosterone secretion in response to the administration of these two drugs was explored to examine the role of the 5-HT4 receptor in aldosterone secretion. Methods: Following a single-blind, random design, ten normal male volunteers received one of the following regimens on three occasions, with at least 2-week intervals: metoclopramide 10 mg i.v.; tropisetron 5 mg by slow i.v.i., or; tropisetron by slow i.v.i., followed by 10 mg metoclopramide i.v. Results: In response to metoclopramide alone the mean plasma aldosterone level rose significantly to 149% of basal level and remained significantly elevated for the next 20 min. With tropisetron alone, there was a significant 37.8% drop at 60 min and the aldosterone levels remained low for the duration of the experiment. Metoclopramide reversed the decline mediated by tropisetron significantly at 30 and 90 min. Aldosterone levels after the latter regimen also did not differ significantly from baseline at any time period. Conclusion: These results would suggest the existence of a tonic stimulatory influence of 5-HT via 5-HT4 receptors on aldosterone secretion, which could be augmented by metoclopramide and blocked by tropisetron. However, the effect of tropisetron per se should be interpreted with caution given the lack of a saline group.