Effects of enhancement and antagonism of 5-hydroxytryptamine activity on metoclopramide-induced aldosterone secretion in man

Abstract

This study examines the contribution of the serotonergic system to metoclopramide-induced aldosterone secretion. Six normal male volunteers, at 13 h, 9 h, and 2 h before the i.v. bolus of 10 mg metoclopramide, received the following pre-treatments in a single-blind cross-over randomized sequence: fluoxetine 20 mg, metergoline 6 mg, pizotifen 0.5 mg, or methysergide 2 mg. One regimen consisted of metoclopramide alone. Pizotifen and fluoxetine pre-treatment increased metoclopramide-induced aldosterone secretion significantly after 15 min, for the duration in the case of fluoxetine, and up to 90 min with pizotifen. The increase with metergoline was never significant, while methysergide had a negligible influence. Serotonin is postulated to play an intermediary role in acetylcholine-facilitated aldosterone release. The mechanism of fluoxetine-mediated serotonin increase is a re-uptake inhibition and that of pizotifen is suggested to be the elimination of an auto-inhibitory mechanism.