Effects of pre-treatment with desfenfluramine and venlafaxine on metoclopramide-induced aldosterone secretion in male volunteers

We have used a placebo-controlled study to compare the effect of acute pre-treatment with dexfenfluramine and fluoxetine on the plasma aldosterone response to metoclopramide. Ten healthy ambulatory male volunteers participated. Following a single-blind, random design, on each experimental day each volunteer received metoclopramide as an i.v, bolus of 10 mg at 07:00 h. They were pre-treated at 22:00 h the previous evening and 05:00 h in the morning with one of the following: venlafaxine 37.5 mg; dexfenfluramine 30 mg; placebo. In response to metoclopramide administration C-max (maximum plasma concentration) was significantly higher than baseline with placebo (P < 0.004), venlafaxine (P < 0.009) and dexfenfluramine (P < 0.004). The AUC (area under the plasma concentration-time curve) of dexfenfluramine was significantly larger than both that with placebo (P < 0.005) and venlafaxine (P < 0.006), while that of the latter was significantly smaller than that of placebo (P < 0.01). Dexfenfluramine, a 5-HT releaser reuptake blocker, mediated an expected augmentation of metoclopramide-induced aldosterone secretion, while venlafaxine blunted this response, possibly through 5-HT4 receptor antagonism. This could suggest the existence of a tonic stimulatory influence of 5-HT via 5-HT4 receptors on aldosterone secretion. Med Sci Res 26:573-575 (C) 1998 Lippincott Williams & Wilkins.