Effects of pretreatment with dexfenfluramine and fluoxetine on metoclopramide-induced aldosterone secretion in healthy volunteers

Objective: The present placebo-controlled study was designed to compare the effect of acute pretreatment with dexfenfluramine and fluoxetine on the plasma aldosterone response to metoclopramide. Study Participants and Design: Ten healthy ambulatory male volunteers participated. Following a single-blind, randomised design, each volunteer received metoclopramide as an intravenous bolus of 10mg at 0700 hours on each experimental day. Participants were pretreated at 2200 hours the previous evening and 0500 hours in the morning with one of the following: fluoxetine 20mg, dexfenfluramine 30mg, or placebo. Results: In response to metoclopramide administration, the maximum concentration was significantly higher (p = 0.004) than baseline with placebo, fluoxetine and dexfenfluramine. The area under the curve of dexfenfluramine was significantly larger than that with both placebo (p = 0.007) and fluoxetine (p = 0.004), while that of fluoxetine was significantly larger than that of placebo (p = 0.01). Conclusion: Acute pretreatment with both dexfenfluramine and fluoxetine caused an enhancement of metoclopramide-induced aldosterone secretion, probably by augmenting serotonergic neurotransmission via serotonin (5-HT)(4) receptors. The plasma aldosterone levels were significantly higher with dexfenfluramine compared with fluoxetine, probably as a result of larger 5-HT concentrations being available for stimulation of glomerulosa cell activity.