Effects of levetiracetam on astroglial release of kynurenine-pathway metabolites

British Journal of Pharmacology
Kouji Fukuyama, Motohiro Okada

Abstract

Several preclinical studies have demonstrated the unique profiles of levetiracetam (LEV), inhibits spontaneous absence epilepsy models but does not affect traditional convulsion models; however, the detailed pharmacological mechanisms of action of LEV remain to be clarified. We determined the interaction between LEV and IFNγ regarding astroglial release of anti-convulsive (kynurenic acid and xanthurenic acid), pro-convulsive (quinolinic acid) and anti-convulsive but pro-absence (cinnabarinic acid) kynurenine-pathway metabolites from rat cortical primary cultured astrocytes using ultra-HPLC equipped with MS. IFNγ increased basal astroglial release of cinnabarinic acid and quinolinic acid but decreased that of kynurenic acid and xanthurenic acid. IFNγ enhanced inositol 1,4,5-trisphosphate (IP3 ) receptor agonist (adenophostin A, AdA)-induced astroglial release of kynurenine-pathway metabolites, without affecting AMPA-induced release. LEV increased basal astroglial release of kynurenic acid and xanthurenic acid without affecting cinnabarinic acid or quinolinic acid. Chronic and acute LEV administration inhibited AMPA- and AdA-induced kynurenine-pathway metabolite release. Upon chronic administration, LEV enhanced stimulatory effec...Continue Reading

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Citations

Nov 5, 2020·International Journal of Molecular Sciences·Kouji Fukuyama, Motohiro Okada
Jan 6, 2021·International Journal of Molecular Sciences·Motohiro OkadaTakashi Shiroyama
Mar 12, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Motohiro OkadaYuto Ueda
Apr 5, 2021·Current Opinion in Immunology·Michael PlattenChristiane A Opitz
May 1, 2021·International Journal of Molecular Sciences·Kouji FukuyamaMotohiro Okada
Mar 11, 2021·British Journal of Pharmacology·Motohiro Okada
Jun 3, 2021·International Journal of Molecular Sciences·Kouji Fukuyama, Motohiro Okada

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