Levetiracetam inhibits both ryanodine and IP3 receptor activated calcium induced calcium release in hippocampal neurons in culture.

Neuroscience Letters
Nisha NagarkattiRobert J DeLorenzo

Abstract

Epilepsy affects approximately 1% of the population worldwide, and there is a pressing need to develop new anti-epileptic drugs (AEDs) and understand their mechanisms of action. Levetiracetam (LEV) is a novel AED and despite its increasingly widespread clinical use, its mechanism of action is as yet undetermined. Intracellular calcium ([Ca2+]i) regulation by both inositol 1,4,5-triphosphate receptors (IP3R) and ryanodine receptors (RyR) has been implicated in epileptogenesis and the maintenance of epilepsy. To this end, we investigated the effect of LEV on RyR and IP3R activated calcium-induced calcium release (CICR) in hippocampal neuronal cultures. RyR-mediated CICR was stimulated using the well-characterized RyR activator, caffeine. Caffeine (10mM) caused a significant increase in [Ca2+]i in hippocampal neurons. Treatment with LEV (33 microM) prior to stimulation of RyR-mediated CICR by caffeine led to a 61% decrease in the caffeine induced peak height of [Ca2+]i when compared to the control. Bradykinin stimulates IP3R-activated CICR-to test the effect of LEV on IP3R-mediated CICR, bradykinin (1 microM) was used to stimulate cells pre-treated with LEV (100 microM). The data showed that LEV caused a 74% decrease in IP3R-media...Continue Reading

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Citations

Sep 18, 2009·Alcohol and Alcoholism : International Journal of the Medical Council on Alcoholism·Tracy R ButlerMark A Prendergast
Apr 10, 2012·Neuroscience Letters·Kouji FukuyamaMotohiro Okada
May 4, 2010·Epilepsy Research·Linda PaulsonRobrecht Raedt
Jul 19, 2011·Alcoholism, Clinical and Experimental Research·Tracy R Butler, Mark A Prendergast
Feb 13, 2009·Seizure : the Journal of the British Epilepsy Association·Doru Georg Margineanu, Henrik Klitgaard
Jan 26, 2013·Neuropharmacology·Joseph A McQuailMichelle M Nicolle
Jun 22, 2016·Annals of the New York Academy of Sciences·Laxmikant S DeshpandeRobert J DeLorenzo
Jul 29, 2016·Epilepsia·Melissa L Barker-HaliskiH Steve White
Jun 1, 2017·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Rebecca P HabermanMichela Gallagher
Aug 29, 2018·British Journal of Pharmacology·Kouji Fukuyama, Motohiro Okada
Jan 14, 2018·European Journal of Human Genetics : EJHG·Xia LiQing Kenneth Wang
Jun 6, 2009·Expert Review of Neurotherapeutics·Nisha NagarkattiRobert J DeLorenzo
Apr 6, 2012·Journal of Receptor and Signal Transduction Research·Mete Ozcan, Ahmet Ayar
Aug 12, 2016·Physiological Reviews·Michael J Berridge
Sep 23, 2020·Annals of the New York Academy of Sciences·Laxmikant S DeshpandeRobert J DeLorenzo
Mar 21, 2017·Pharmacological Reports : PR·Krzysztof SendrowskiWojciech Sobaniec
Aug 10, 2019·Frontiers in Cellular Neuroscience·Junxiu LiuDavid M Halliday
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Aug 26, 2010·Neuroreport·Doru Georg Margineanu
May 1, 2017·Pharmacological Reports : PR·Krzysztof SendrowskiWojciech Sobaniec

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