The effect of losigamone (AO-33) on electrical activity and excitatory amino acid release in mouse cortical slices

British Journal of Pharmacology
J SrinivasanJ A Davies

Abstract

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 microM and above. 3. NMDA-induced depolarizations were significantly reduced by losigamone at concentrations of 25 microM and above. Losigamone had no effect on AMPA-induced depolarizations. 4. Veratridine (20 microM) and potassium (60 mM) 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 microM and above, while potassium-stimulated release was significantly reduced by losigamone at 200 microM. 5. NMDA antagonism and inhibition of excitatory amino acid release may contribute to the anticonvulsant effect of losigamone.

References

Jul 1, 1992·Epilepsy Research·B S Meldrum
Oct 20, 1992·European Journal of Pharmacology·A J PalmerD Lodge
Dec 8, 1992·European Journal of Pharmacology·B G Dickie, J A Davies
Apr 1, 1980·Journal of Neuroscience Methods·M C Minchin
Jun 1, 1993·Journal of Ethnopharmacology·B AbilaJ A Davies
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Citations

Sep 16, 2003·Epilepsy Research·M BaulacUNKNOWN Losigamone Study Group
Dec 1, 1999·British Journal of Pharmacology·F A Jones, J A Davies
Jan 5, 2001·Expert Opinion on Investigational Drugs·M C Walker, J W Sander
May 16, 2009·Pharmacological Reports : PR·Jarogniew J Luszczki
Dec 19, 2012·Epilepsia·Pablo M Casillas-EspinosaTerence J O'Brien
Apr 8, 2006·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Kinga K BorowiczStanislaw J Czuczwar
Oct 29, 2005·European Journal of Pharmacology·Brian P Kirby, Graham G Shaw

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