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The effect of losigamone (AO‐33) on electrical activity and excitatory amino acid release in mouse cortical slices
Author(s) -
Srinivasan Jayashri,
Richens Alan,
Davies John A.
Publication year - 1997
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0701539
Subject(s) - veratridine , excitatory postsynaptic potential , chemistry , nmda receptor , glutamate receptor , ampa receptor , biophysics , potassium , pharmacology , amino acid , neuroscience , biochemistry , biology , sodium , receptor , sodium channel , organic chemistry
1 Losigamone is a novel anticonvulsant the mechanism of action of which is not known. This study investigated the effect of losigamone on spontaneous, NMDA‐ and AMPA‐induced depolarizations in the cortical wedge preparation of the DBA/2 mouse (which are susceptible to sound‐induced seizures) and on endogenous amino acid release from BALB/c mouse cortical slices. 2 Cortical wedges exhibit spontaneous depolarizations in magnesium‐free medium and losigamone was effective in significantly reducing these spontaneous depolarizations at concentrations of 100 μ M and above. 3 NMDA‐induced depolarizations were significantly reduced by losigamone at concentrations of 25 μ M and above. Losigamone had no effect on AMPA‐induced depolarizations. 4 Veratridine (20 μ M ) and potassium (60 m M ) were used to stimulate the release of amino acids from mouse cortex. Veratridine‐stimulated release of glutamate was significantly reduced by losigamone at concentrations of 100 μ M and above, while potassium‐stimulated release was significantly reduced by losigamone at 200 μ M . 5 NMDA antagonism and inhibition of excitatory amino acid release may contribute to the anticonvulsant effect of losigamone.