A. Draguhn et al., LOSIGAMONE DECREASES SPONTANEOUS SYNAPTIC ACTIVITY IN CULTURED HIPPOCAMPAL-NEURONS, European journal of pharmacology, 325(2-3), 1997, pp. 245-251
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.