Losigamone decreases spontaneous synaptic activity in cultured hippocampal neurons

Losigamone is a new antiepileptic drug with an unknown mechanism of action. Here we report on the effects of losigamone on the synaptic activity in a network of cultured rat hippocampal neurons. Losigamone dose dependently reduced the frequency of spontaneous synaptic events without affecting the mean current amplitude. The drug affected equally the isolated inhibitory as well as excitatory postsynaptic currents. Miniature postsynaptic currents were not altered by losigamone, suggesting that the mechanism of action depends on functional Na+ channels. Consistent with these findings, the drug decreased the frequency of spontaneous action potentials and suppressed repetitive firing of neurons. Thus, losigamone generally depresses synaptic activity in a neuronal network without selectively modulating a specific postsynaptic receptor type. We conclude that losigamone acts via a presynaptic mechanism reducing neuronal excitability.