Figure 1.

Potential mechanism of fenfluramine. Epilepsy is thought to generate an imbalance between inhibitory GABA signaling and excitatory glutamatergic signaling, leading to seizures. In the above figures, the balance between inhibitory and excitatory signaling is indicated by the blue balance beam. (A) Too much glutamate signaling results in seizures (e.g., the right arm of the balance beam moves upward). (B) Balance between inhibition and excitation is restored by the dual activities of fenfluramine: the activity of fenfluramine at 5-HT receptors results in increased GABA signaling, boosting inhibition, while the activity of fenfluramine at the Sigma1R reduces glutamatergic signaling, decreasing excitation. This mechanism is consistent with much, but not all, of the published research and is presented as a working model. 5-HT, serotonin; GABA, gamma aminobutyric acid; Sigma1R, Sigma1 receptor.