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 possi bly be ascribed to agonist activity at 5-HT4 receptors. The 5-HT3 anta gonist tropisetron is thought to act as an antagonist at 5-HT4 recepto rs. In the present study aldosterone secretion in response to the admi nistration of these two drugs was explored to examine the role of the 5-HT4 receptor in aldosterone secretion.Methods: Following a single-bl ind, random design, ten normal male volunteers received one of the fol lowing regimens on three occasions, with at least 2-week intervals: me toclopramide 10 mg i.v.; tropisetron 5 mg by slow i.v.i., or; tropiset ron by slow i.v.i., followed by 10 mg metoclopramide i.v. Results: In response to metoclopramide alone the mean plasma aldosterone level ros e significantly to 149% of basal level and remained significantly elev ated for the next 20 min. With tropisetron alone, there was a signific ant 37.8% drop at 60 min and the aldosterone levels remained low for t he duration of the experiment. Metoclopramide reversed the decline med iated by tropisetron significantly at 30 and 90 min. Aldosterone level s after the latter regimen also did not differ significantly from base line at any time period. Conclusion: These results would suggest the e xistence of a tonic stimulatory influence of 5-HT via 5-HT4 receptors on aldosterone secretion, which could be augmented by metoclopramide a nd blocked by tropisetron. However, the effect of tropisetron per se s hould be interpreted with caution given the lack of a saline group.