FIGURE 2.

Serotonergic mechanisms of action of fenfluramine: (1) increase of GABAergic dendritic arborization via 5‐HT and GABAergic activity ¹⁶⁸ ; (2) decrease of serotonin reuptake by inhibition of SERT ¹⁶⁹ ; (3) increase of fusion and release of synaptic vesicles ¹⁷⁰ ; (4) the two previous modulatory lead to an increase of 5‐HT in the synaptic cleft and thereby stimulation of 5‐HT receptor subtypes; and (5) fenfluramine directly stimulates at least five serotonin (5‐HT) receptor subtypes (5‐HT_1D,2A,2C,4,7) (zebrafish and mice data), ¹³ , ¹⁷¹ thereby increasing gamma‐aminobutyric acid inhibitory input and decreasing glutaminergic excitatory output. Regarding the sigma receptor modulation, we refer to Martin et al 2020. ¹² 5‐HT = serotonin; GABA = gamma aminobutyric acid; GLUT = glutamine; SERT = serotonin transporter