The synaptic vesicle glycoprotein 2A ligand levetiracetam inhibits presynaptic Ca2+ channels through an intracellular pathway

Molecular Pharmacology
Christian VoglGary J Stephens

Abstract

Levetiracetam (LEV) is a prominent antiepileptic drug that binds to neuronal synaptic vesicle glycoprotein 2A protein and has reported effects on ion channels, but with a poorly defined mechanism of action. We investigated inhibition of voltage-dependent Ca(2+) (Ca(V)) channels as a potential mechanism through which LEV exerts effects on neuronal activity. We used electrophysiological methods to investigate the effects of LEV on cholinergic synaptic transmission and Ca(V) channel activity in superior cervical ganglion neurons (SCGNs). In parallel, we investigated the effects of the inactive LEV R-enantiomer, (R)-α-ethyl-2-oxo-1-pyrrolidine acetamide (UCB L060). LEV but not UCB L060 (each at 100 μM) inhibited synaptic transmission between SCGNs in long-term culture in a time-dependent manner, significantly reducing excitatory postsynaptic potentials after a ≥30-min application. In isolated SCGNs, LEV pretreatment (≥1 h) but not short-term application (5 min) significantly inhibited whole-cell Ba(2+) current (I(Ba)) amplitude. In current-clamp recordings, LEV reduced the amplitude of the afterhyperpolarizing potential in a Ca(2+)-dependent manner but also increased the action potential latency in a Ca(2+)-independent manner, whic...Continue Reading

References

Sep 3, 1998·European Journal of Pharmacology·H KlitgaardE Wülfert
Dec 28, 1999·Proceedings of the National Academy of Sciences of the United States of America·K M CrowderS M Bajjalieh
Mar 18, 2000·Pharmacology & Therapeutics·P N Patsalos
Jul 24, 2001·Seizure : the Journal of the British Epilepsy Association·C ZonaD G Margineanu
Aug 3, 2001·Nature Cell Biology·T Xu, S M Bajjalieh
Mar 7, 2002·Epilepsia·E A LukyanetzP G Kostyuk
Feb 26, 2003·Proceedings of the National Academy of Sciences of the United States of America·Sumiko MochidaWilliam A Catterall
Oct 14, 2003·European Journal of Pharmacology·Michel GillardPierre Chatelain
Jan 23, 2004·Journal of Medicinal Chemistry·Benoit M KendaPhilippe Michel
Jun 24, 2004·Proceedings of the National Academy of Sciences of the United States of America·Berkley A LynchBruno Fuks
Jan 27, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Kenneth L CusterSandra M Bajjalieh
Mar 18, 2006·Science·Min DongEdwin R Chapman
Apr 1, 2006·Stroke; a Journal of Cerebral Circulation·Cinzia CostaPaolo Calabresi
Apr 28, 2007·CNS Drug Reviews·Tim De SmedtPaul Boon
Sep 6, 2008·Cephalalgia : an International Journal of Headache·G MartellaP Calabresi
Sep 26, 2008·Molecular Biology of the Cell·Min DongEdwin R Chapman
Jan 30, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Wen-Pin Chang, Thomas C Südhof
Aug 5, 2009·Seizure : the Journal of the British Epilepsy Association·Xiao-Feng Yang, Steven M Rothman
Nov 17, 2009·Epilepsy Research·Cristina ZonaDoru Georg Margineanu
Dec 3, 2010·PLoS Pathogens·Felix L YehEdwin R Chapman
Jul 1, 2008·Therapeutic Advances in Neurological Disorders·Rainer SurgesMatthew C Walker
Apr 28, 2011·The Journal of Physiology·Giovanna BucciGary J Stephens
Jun 10, 2011·Journal of Neurophysiology·Anna L MeehanSteven M Rothman
Jan 6, 2012·PloS One·Amy NowackSandra M Bajjalieh

❮ Previous
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Citations

Oct 25, 2012·Neuropsychiatric Disease and Treatment·Frank Mc Besag, Philip N Patsalos
Jan 2, 2014·International Journal of Molecular Sciences·Hanna Algattas, Jason H Huang
Jul 9, 2014·Journal of Neurosciences in Rural Practice·Ather Muneer
Feb 21, 2016·Environmental Toxicology and Pharmacology·Oytun ErbaşDilek Taşkıran
Jan 23, 2016·Diabetes Research and Clinical Practice·Oytun ErbaşDilek Taşkıran
Oct 31, 2015·Epilepsia·Xiaofeng YangJanet M Dubinsky
Oct 24, 2014·Annals of General Psychiatry·Kazuhiko YamamuroToshifumi Kishimoto
Sep 1, 2015·Epilepsy Research·Xiaofeng YangJanet M Dubinsky
Dec 17, 2015·Journal of Neurotrauma·Megan BrowningPatrick M Kochanek
Dec 19, 2012·Epilepsia·Pablo M Casillas-EspinosaTerence J O'Brien
Dec 3, 2014·CNS Neuroscience & Therapeutics·Isabelle NiespodzianyChristian Wolff
Aug 1, 2015·Proceedings of the National Academy of Sciences of the United States of America·Takayuki OhnishiMinako Hoshi
Aug 21, 2013·Journal of Investigative Surgery : the Official Journal of the Academy of Surgical Research·Oytun ErbaşGönül Peker
Apr 22, 2015·CNS Drugs·Christopher J HammondAlbert J Arias
Aug 28, 2013·Journal of Psychiatric Research·Hubertus HimmerichUlrich Sack
Sep 12, 2013·European Journal of Pharmacology·Trond MyhrerPål Aas
Sep 4, 2012·Biochemical Pharmacology·S Alisha Epps, David Weinshenker
Dec 23, 2015·Journal of Feline Medicine and Surgery·Mark LowrieLaurent Garosi
Oct 17, 2019·Molecular Pain·Solomiya TsymbalyukJ Marc Simard
Jan 26, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Klaudia CybulskaMark Rijpkema
Jun 8, 2015·Journal of Clinical Psychopharmacology·Steven L DubovskyJordan C Serotte
Jun 17, 2020·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Majken B ThomsenAnne M Landau
Sep 27, 2018·Current Treatment Options in Neurology·Erin Feinstein, Ruth Walker
Sep 17, 2019·Therapeutic Advances in Neurological Disorders·Bernhard J Steinhoff, Anke M Staack
Aug 22, 2018·Proceedings of the National Academy of Sciences of the United States of America·Te-Chen TzengDouglas T Golenbock
Oct 16, 2018·Frontiers in Pharmacology·Jaya KumarSrijit Das
Nov 30, 2019·Frontiers in Neurology·Irina GurevicieneHeikki Tanila
Feb 14, 2017·Journal of Medical Case Reports·Samantha SterkelGeorge Michel
May 13, 2015·The Journal of Pediatric Pharmacology and Therapeutics : JPPT : the Official Journal of PPAG·Allison L MrukNoelle R Leung
Jan 20, 2021·Open Biology·Sasi S Senga, Richard P Grose
Jan 26, 2021·Frontiers in Molecular Neuroscience·Audrey Hector, Jonathan Brouillette

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