Modafinil prevents glutamate cytotoxicity in cultured cortical neurons

THE ability of modafinil (Modiodal®) to protect cortical neurons from glutamate-induced degeneration was evaluated by measuring electrically evoked [ 3 H]GABA release and [ 3 H]GABA uptake in primary cerebral cortical cultures. In normal cells, electrical stimulation (10 Hz, 2 min) increased [ 3 H]GABA release (FR-NER St 1 = 0.77 ± 0.14; St 2 /St 1 ratio = 0.94 ± 0.02). The exposure of sister cells to glutamate, reduced electrically evoked [ 3 H]GABA release (FR-NER St 1 = 0.40 ± 0.05; St 2 /St 1 ratio = 0.60 ± 0.08). Modafinil (0.3-1 μM) prevented the glutamate-induced reduction of the St 2 /St 1 ratio (0.85 ± 0.11; 0.88 ± 0.05, respectively). A similar protective effect was observed for [ 3 H]GABA uptake. These findings suggest that modafinil may be neuroprotective in that it attenuates glutamate-induced excitotoxicity in cortical neurons.