PMID: 9187275Jun 1, 1997Paper

Carbamazepine inhibition of neuronal Na+ currents: quantitative distinction from phenytoin and possible therapeutic implications

Molecular Pharmacology
C C KuoR C Chen

Abstract

Carbamazepine and phenytoin, two of the most commonly prescribed antiepileptic drugs, have been proposed to share a similar mechanism of action by use-dependent inhibition of Na+ channels. The proposed similar mechanism of action, however, cannot explain the common clinical experiences that the two drugs are different; in some patients, one drug may be more effective than the other. This may occur even when optimal therapeutic concentrations are reached with both medications in plasma or the cerebrospinal fluid. In this study, we show that the action of the two drugs on Na+ channels are quantitatively very different. The affinity between inactivated Na+ channels and carbamazepine (apparent dissociation constant approximately 25 microM) is approximately 3 times lower than that of phenytoin, yet the binding rate constant of carbamazepine onto the inactivated Na+ channels is approximately 38,000 M(-1)/sec(-1), or approximately 5 times faster than that of phenytoin. It is speculated that carbamazepine may be more effective than phenytoin in treating seizures whose ictal depolarization shift is relatively short, whereas a better response to phenytoin may imply abnormal discharges characterized by more prolonged depolarization.

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Citations

Sep 6, 2001·Journal of Neurophysiology·D KueblerM A Tanouye
Apr 1, 2003·Annals of Neurology·Stefan RemyHeinz Beck
Mar 22, 2005·British Journal of Pharmacology·Victor I IlyinRichard M Woodward
Feb 22, 2012·Science Translational Medicine·Elizabeth TringhamTerrance P Snutch
Feb 7, 2017·Investigational New Drugs·Karl J FöhrOliver Adolph
Feb 1, 2019·Annual Review of Neuroscience·Sulayman D Dib-Hajj, Stephen G Waxman
Jun 5, 2020·Science Advances·Mickaël ZbiliDominique Debanne
Jun 23, 2005·Epilepsia·Emilio Perucca
Apr 13, 2005·The Journal of General Physiology·Ya-Chin Yang, Chung-Chin Kuo
May 4, 2011·Molecular Pharmacology·Sooyeon Jo, Bruce P Bean
Jan 8, 2020·Molecular Pain·Eder GambetaGerald W. Zamponi
Nov 9, 2002·Epilepsia·Rüdiger Köhling
Dec 15, 2012·Journal of Neuroscience Research·Isabelle NiespodzianyChristian Wolff
Feb 23, 2011·Neurochemical Research·Guangqin ZhangHeming Wei
Nov 11, 2015·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Rikke S Møller, Katrine M Johannesen
Dec 10, 2013·Molecular Pharmacology·Sooyeon Jo, Bruce P Bean
Sep 17, 2018·The Journal of Biological Chemistry·Mohammad-Reza GhovanlooSamuel J Goodchild
Oct 10, 2013·Toxicological Sciences : an Official Journal of the Society of Toxicology·Patrícia Alves Maia GuidineMichel Bernanos Soares Mesquita
Apr 2, 2011·Epilepsia·Christopher H ThompsonAlfred L George
Feb 17, 2015·Epilepsia·Elizabeth García-PérezJohn F Wesseling
Jun 27, 2019·Pharmaceuticals·Daria A BelinskaiaNatalia N Shestakova

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