LOSIGAMONE DECREASES SPONTANEOUS SYNAPTIC ACTIVITY IN CULTURED HIPPOCAMPAL-NEURONS

Losigamone is a new antiepileptic drug with an unknown mechanism of ac tion. Here we report on the effects of losigamone on the synaptic acti vity in a network of cultured rat hippocampal neurons. Losigamone dose dependently reduced the frequency of spontaneous synaptic events with out affecting the mean current amplitude. The drug affected equally th e isolated inhibitory as well as excitatory postsynaptic currents. Min iature postsynaptic currents were not altered by losigamone, suggestin g that the mechanism of action depends on functional Na+ channels. Con sistent with these findings, the drug decreased the frequency of spont aneous action potentials and suppressed repetitive firing of neurons. Thus, losigamone generally depresses synaptic activity in a neuronal n etwork without selectively modulating a specific postsynaptic receptor type. We conclude that losigamone acts via a presynaptic mechanism re ducing neuronal excitability.