EFFECTS OF PRETREATMENT 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 aldos terone response to metoclopramide. Ten healthy ambulatory male volunte ers participated. Following a single-blind, random design, on each exp erimental 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 eve ning and 05:00 h in the morning with one of the following: venlafaxine 37.5 mg; dexfenfluramine 30 mg; placebo. In response to metoclopramid e administration C-max (maximum plasma concentration) was significantl y higher than baseline with placebo (P < 0.004), venlafaxine (P < 0.00 9) and dexfenfluramine (P < 0.004). The AUC (area under the plasma con centration-time curve) of dexfenfluramine was significantly larger tha n both that with placebo (P < 0.005) and venlafaxine (P < 0.006), whil e 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 secreti on, while venlafaxine blunted this response, possibly through 5-HT4 re ceptor antagonism. This could suggest the existence of a tonic stimula tory influence of 5-HT via 5-HT4 receptors on aldosterone secretion. M ed Sci Res 26:573-575 (C) 1998 Lippincott Williams & Wilkins.