G. Bonanno, A. Fassio, Paolo Severi
Sep 1, 1994
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Journal
Journal of Neurochemistry
Abstract
Abstract: Fenfluramine is the most widely used anorexigenic drug in humans. In animal experiments d‐fenfluramine has been shown to act as a potent releaser of brain serotonin [5‐hydroxytryptamine (5‐HT)]. Here we have investigated the effects of d‐fenfluramine on the release of [3H]5‐HT from isolated nerve endings of human neocortex. The drug elicited release of unmetabolized [3H]5‐HT, and this effect was concentration dependent. However, the mechanism of release seems to differ profoundly depending on the concentrations of d‐fenfluramine used. At 5 µM, the release of [3H]5‐HT was blocked by the 5‐HT transporter inhibitor fluoxetine and was Ca2+ independent and insensitive to the human autoreceptor 5‐HT1D agonist sumatriptan. The release of [3H]5‐HT elicited by 0.5 µMd‐fenfluramine was similarly blocked by fluoxetine, but it was strongly Ca2+ dependent and sensitive to sumatriptan. It is suggested that, at relatively high concentrations, d‐fenfluramine largely diffuses into serotonergic terminals and causes release of 5‐HT through the 5‐HT carrier working in the inside‐outside direction; at relatively low concentrations d‐fenfluramine enters the terminals through the 5‐HT transporter but elicits release of 5‐HT by an exocytotic‐like mechanism.