Differences between d-fenfluramine and d-norfenfluramine in serotonin presynaptic mechanisms.

The abilities of d-fenfluramine (d-F) and that of d-norfenfluramine (d-NF) to inhibit [3H]serotonin ([3H]5-HT) accumulation in normal and reserpinized synaptosomes were compared to establish to what extent the serotonin-releasing activity of the two drugs might contribute to reduced accumulation of [3H]5-HT. The results indicate that the inhibitory action of (d-NF) on [3H]5-HT accumulation is due principally to its ability to release [3H]5-HT. In contrast, the interference of release in accumulation studies does not seem to play an important role for d-F, suggesting that release from the granular pool and true uptake inhibition are two different mechanisms by which d-F affects serotonin neurons in vitro.