Inhibition of multidrug transporters by verapamil or probenecid does not alter blood-brain barrier penetration of levetiracetam in rats.

Abstract:

:Overexpression of multidrug efflux transporters such as P-glycoprotein (Pgp; ABCB1) or multidrug resistance proteins (MRPs; ABCC) in the blood-brain barrier has recently been suggested to explain, at least in part, pharmacoresistance in epilepsy, which affects about 30% of all patients with this common brain disorder. The novel antiepileptic drug (AED) levetiracetam (LEV) is an effective and well tolerated drug in many patients with otherwise AED-refractory epilepsy. One explanation for the favorable efficacy of LEV in pharmacoresistant patients would be that LEV is not a substrate for Pgp or MRPs in the BBB. In the present study, we used in vivo microdialysis in rats to study whether the concentration of LEV in the extracellular fluid of the cerebral cortex can be modulated by inhibition of Pgp or MRPs, using the Pgp inhibitor verapamil and the MRP1/2 inhibitor probenecid. Local perfusion with verapamil or probenecid via the microdialysis probe did not increase the extracellular brain concentration of LEV, which is in contrast to various other AEDs which have been studied previously by the same experimental protocol in this model. The data indicate that brain uptake of LEV is not affected by Pgp or MRP1/2 which may be an important reason for its antiepileptic efficacy in patients whose seizures are poorly controlled by other AEDs.

journal_name

Epilepsy Res

journal_title

Epilepsy research

authors

Potschka H,Baltes S,Löscher W

doi

10.1016/j.eplepsyres.2003.12.007

subject

Has Abstract

pub_date

2004-02-01 00:00:00

pages

85-91

issue

2-3

eissn

0920-1211

issn

1872-6844

pii

S0920121104000221

journal_volume

58

pub_type

杂志文章
  • Do dichotic word listening asymmetries predict side of temporal lobe seizure onset?

    abstract::Dichotic word listening asymmetries are thought to be useful in predicting side of temporal lobe dysfunction. However, little direct evidence exists to support this assumption in practice, especially in patients with subtle epileptogenic lesions. To determine if word listening ear asymmetries are valid predictors of s...

    journal_title:Epilepsy research

    pub_type: 杂志文章

    doi:10.1016/0920-1211(94)90025-6

    authors: Lee GP,Loring DW,Varney NR,Roberts RJ,Newell JR,Martin JA,Smith JR,King DW,Meador KJ,Murro AM

    更新日期:1994-10-01 00:00:00

  • Brain injury-induced enhanced limbic epileptogenesis: anatomical and physiological parallels to an animal model of temporal lobe epilepsy.

    abstract::Traumatic brain injury (TBI) is a leading cause of symptomatic epilepsy in young adults. This study examined physiological and anatomical epileptogenic consequences of a prior incident of TBI in rats. Rats were subjected to a fluid percussion brain injury one week prior to experimentation, and in vitro electrophysiolo...

    journal_title:Epilepsy research

    pub_type: 杂志文章

    doi:10.1016/s0920-1211(96)00044-7

    authors: Coulter DA,Rafiq A,Shumate M,Gong QZ,DeLorenzo RJ,Lyeth BG

    更新日期:1996-12-01 00:00:00

  • Validation of the Chinese version of the Liverpool Adverse Events Profile in patients with epilepsy.

    abstract::The objective of the study was to validate the Chinese version of The Liverpool Adverse Events Profile (LAEP) in patients with epilepsy. The scale was translated from the English version into a Chinese version and was then back-translated to examine its accuracy. Content validity, concurrent validity, and construct va...

    journal_title:Epilepsy research

    pub_type: 杂志文章

    doi:10.1016/j.eplepsyres.2011.01.008

    authors: Chen HF,Tsai YF,Shih MS,Chen JC

    更新日期:2011-03-01 00:00:00

  • Inhalation of 10% carbon dioxide rapidly terminates Scn1a mutation-related hyperthermia-induced seizures.

    abstract::The aim of this study was to assess the anticonvulsant effect of carbon dioxide (CO2) on Scn1a mutation-related febrile seizures. We examined physiological changes in the blood gas levels after the induction of hyperthermia-induced seizures (HISs), which were associated with the Scn1a missense mutation. We determined ...

    journal_title:Epilepsy research

    pub_type: 杂志文章

    doi:10.1016/j.eplepsyres.2013.01.003

    authors: Ohmori I,Hayashi K,Wang H,Ouchida M,Fujita N,Inoue T,Michiue H,Nishiki T,Matsui H

    更新日期:2013-07-01 00:00:00

  • A meta-analysis of voxel-based morphometry studies on unilateral refractory temporal lobe epilepsy.

    abstract:PURPOSE:To identify consistent results of voxel-based morphometry (VBM) studies in unilateral refractory temporal lobe epilepsy (TLE). METHODS:Whole-brain VBM studies comparing refractory TLE patients with healthy controls (HC) were systematically searched in PubMed, ISI Web of Science, Embase, and Medline databases f...

    journal_title:Epilepsy research

    pub_type: 杂志文章,meta分析,评审

    doi:10.1016/j.eplepsyres.2011.10.002

    authors: Li J,Zhang Z,Shang H

    更新日期:2012-02-01 00:00:00

  • The ketogenic diet: from molecular mechanisms to clinical effects.

    abstract::Recent years have witnessed an increased interest from pediatric neurologists, neuropediatricians, epileptologists and general neurologists in the use of the ketogenic diet (KD) for the management of refractory epilepsies, particularly in children and adolescents. This article summarizes current knowledge on various i...

    journal_title:Epilepsy research

    pub_type: 共识发展会议,杂志文章

    doi:10.1016/j.eplepsyres.2005.10.003

    authors: Freeman J,Veggiotti P,Lanzi G,Tagliabue A,Perucca E,Institute of Neurology IRCCS C. Mondino Foundation.

    更新日期:2006-02-01 00:00:00

  • Co-occurrence of major depression or suicide attempt with migraine with aura and risk for unprovoked seizure.

    abstract::We hypothesized and found that the co-occurrence of migraine with aura (MA) with major depression (MD) or with suicide attempt (SA) increases the risk for developing unprovoked seizure more than these conditions alone. Number of conditions showed a linear relationship to seizure risk. This may reflect a new condition ...

    journal_title:Epilepsy research

    pub_type: 杂志文章

    doi:10.1016/j.eplepsyres.2007.05.001

    authors: Hesdorffer DC,Lúdvígsson P,Hauser WA,Olafsson E,Kjartansson O

    更新日期:2007-07-01 00:00:00

  • Hlf is a genetic modifier of epilepsy caused by voltage-gated sodium channel mutations.

    abstract::Mutations in voltage-gated sodium channel genes cause several types of human epilepsies. Often, individuals with the same sodium channel mutation exhibit diverse phenotypes. This suggests that factors beyond the primary mutation influence disease severity, including genetic modifiers. Mouse epilepsy models with voltag...

    journal_title:Epilepsy research

    pub_type: 杂志文章

    doi:10.1016/j.eplepsyres.2015.11.016

    authors: Hawkins NA,Kearney JA

    更新日期:2016-01-01 00:00:00

  • The NMDA antagonist MK-801 suppresses behavioral seizures, augments afterdischarges, but does not block development of perforant path kindling.

    abstract::The role of N-methyl-D-aspartate (NMDA) in the development and expression of kindled seizures was assessed using a crossover design. Rats were stimulated once daily in the perforant path for 10 consecutive days 30 min following daily administration of saline or the NMDA antagonist MK-801 (1.0 mg/kg) (phase I). Five to...

    journal_title:Epilepsy research

    pub_type: 杂志文章

    doi:10.1016/0920-1211(94)90014-0

    authors: Gilbert ME

    更新日期:1994-02-01 00:00:00

  • Safety of an IV formulation of carbamazepine.

    abstract::An intravenous formulation of carbamazepine (CBZ) was administered to 113 (60 male; 53 female) persons with epilepsy aged 19-87 years. Subjects received 100mg of study drug as replacement for 100mg of their usual morning dose of CBZ. There were no significant changes in blood pressure or heart rate suggesting that thi...

    journal_title:Epilepsy research

    pub_type: 杂志文章

    doi:10.1016/j.eplepsyres.2009.01.013

    authors: Conway JM,White JR,Birnbaum AK,Eugene Ramsay R,Pennell PB,Rarick JO,Musib L,Leppik IE,Cloyd JC

    更新日期:2009-04-01 00:00:00

  • Interactions of epileptiform EEG discharges and cognition.

    abstract::Interactions of subclinical epileptiform EEG discharges and cognitive functioning were studied in 91 patients with epilepsy, under video monitoring, to exclude overt clinical ictal phenomena during the investigations. A short-term memory test was presented as an engaging television game, in two versions, using spatial...

    journal_title:Epilepsy research

    pub_type: 杂志文章

    doi:10.1016/0920-1211(87)90031-3

    authors: Binnie CD,Kasteleijn-Nolst Trenité DG,Smit AM,Wilkins AJ

    更新日期:1987-07-01 00:00:00

  • Historical trend toward improved long-term outcome in childhood absence epilepsy.

    abstract::We retrospectively analyzed published studies to investigate historical trends in outcome of childhood absence epilepsy (CAE). We included patients based on onset of absence seizures in childhood, 3 Hz bilateral spike-wave discharges on EEG, and availability of seizure-free outcome data. The primary endpoint was seizu...

    journal_title:Epilepsy research

    pub_type: 历史文章,杂志文章,meta分析

    doi:10.1016/j.eplepsyres.2019.02.013

    authors: Morse E,Giblin K,Chung MH,Dohle C,Berg AT,Blumenfeld H

    更新日期:2019-05-01 00:00:00

  • Age-dependent anticonvulsant action of antagonists of group I glutamate metabotropic receptors in rats.

    abstract:SUMMARY:Metabotropic glutamate receptors (mGluR) may represent a perspective target for anticonvulsant therapy but spectrum of their anticonvulsant effects is not sufficiently known. Our study was aimed at comparison of anticonvulsant actions of antagonists of mGluR1 and mGluR5 subtypes in immature rats. Seven-, 12-, 1...

    journal_title:Epilepsy research

    pub_type: 杂志文章

    doi:10.1016/j.eplepsyres.2008.11.004

    authors: Mares P

    更新日期:2009-02-01 00:00:00

  • Differential sensitivity to inverse agonists of GABA(A)/benzodiazepine receptors in rats with genetic absence-epilepsy.

    abstract::A strain of Wistar rats, genetic absence epilepsy rats from Strasbourg (GAERS), was selected and inbred over 40 generations for occurrence of spontaneous spike-wave discharges characteristic of absence seizures, simultaneously with a strain of non-epileptic rats (NER). GAERS demonstrate an excessive sensitivity to ant...

    journal_title:Epilepsy research

    pub_type: 杂志文章

    doi:10.1016/s0920-1211(01)00292-3

    authors: Vergnes M,Boehrer A,He X,Greney H,Dontenwill M,Cook J,Marescaux C

    更新日期:2001-11-01 00:00:00

  • Increasing structural atrophy and functional isolation of the temporal lobe with duration of disease in temporal lobe epilepsy.

    abstract:BACKGROUND:Due to pharmacoresistant seizures and the underutilization of surgical treatments, a large number of temporal lobe epilepsy (TLE) patients experience seizures for years or decades. The goal of this study was to generate a predictive model of duration of disease with the least number of parameters possible in...

    journal_title:Epilepsy research

    pub_type: 杂志文章

    doi:10.1016/j.eplepsyres.2014.12.006

    authors: Morgan VL,Conrad BN,Abou-Khalil B,Rogers BP,Kang H

    更新日期:2015-02-01 00:00:00

  • alpha-Tocopherol protects against pentylenetetrazol- and methylmalonate-induced convulsions.

    abstract::Increased excitatory amino acid transmission and decreased GABAergic inhibitory responses seem to be important mechanisms in the genesis of convulsions, where reactive oxygen species (ROS) have recently been suggested to play a critical role. Therefore, administration of antioxidants may be potentially beneficial for ...

    journal_title:Epilepsy research

    pub_type: 杂志文章

    doi:10.1016/j.eplepsyres.2005.08.005

    authors: Ribeiro MC,de Avila DS,Schneider CY,Hermes FS,Furian AF,Oliveira MS,Rubin MA,Lehmann M,Krieglstein J,Mello CF

    更新日期:2005-08-01 00:00:00

  • Increased membrane shedding--indicated by an elevation of CD133-enriched membrane particles--into the CSF in partial epilepsy.

    abstract:PURPOSE:Recent analyses provided evidence that human adult cerebrospinal fluid (CSF) in addition to soluble proteins also contains membrane particles that moreover carry the somatic stem cell marker CD133. The significance of CD133 as a potential marker of cellular proliferation, including neurogenesis, remains unresol...

    journal_title:Epilepsy research

    pub_type: 杂志文章

    doi:10.1016/j.eplepsyres.2011.10.029

    authors: Huttner HB,Corbeil D,Thirmeyer C,Coras R,Köhrmann M,Mauer C,Kuramatsu JB,Kloska SP,Doerfler A,Weigel D,Klucken J,Winkler J,Pauli E,Schwab S,Hamer HM,Kasper BS

    更新日期:2012-03-01 00:00:00

  • Epilepsy and prolactin in adults: a clinical review.

    abstract::Serum levels of prolactin may increase as a consequence of epileptic seizures. The hormone release is caused by the propagation of epileptic activity, usually from the temporal lobe to the hypothalamic-pituitary axis. Due to the intensity of the epileptic afterdischarge, a rise is seen in approximately 60% of complex ...

    journal_title:Epilepsy research

    pub_type: 杂志文章,评审

    doi:10.1016/0920-1211(96)00009-5

    authors: Bauer J

    更新日期:1996-05-01 00:00:00

  • Do polio survivors have a higher risk of epilepsy?

    abstract::We planned this study to investigate the frequency of epilepsy in paralytic polio survivors. We analyzed the clinical data of 91 paralytic polio survivors. Patients who had been diagnosed with epilepsy were examined by electroencephalography and brain magnetic resonance imaging. 11 of the 91 patients had epilepsy (12%...

    journal_title:Epilepsy research

    pub_type: 杂志文章

    doi:10.1016/j.eplepsyres.2011.08.019

    authors: Demir CF,Berilgen MS,Mungen B,Bulut S

    更新日期:2012-01-01 00:00:00

  • Congenital brain dysplasias of different genesis can differently affect susceptibility to pilocarpine- or kainic acid-induced seizures in the rat.

    abstract::Interruption of neurogenesis and/or neuronal migration produces brain dysplasia modifying susceptibility to epileptic seizures in adulthood. The course of neurogenesis has a strictly defined time-table. Consequently, the developmental stage at which the interruption occurs determines what functional subsystem potentia...

    journal_title:Epilepsy research

    pub_type: 杂志文章

    doi:10.1016/j.eplepsyres.2005.09.006

    authors: Setkowicz Z,Janicka D,Kowalczyk A,Turlej A,Janeczko K

    更新日期:2005-12-01 00:00:00

  • Electroencephalographic evidence for a dose-related biphasic effect of morphine on bicuculline-induced seizures in the rat.

    abstract::The effects of systemic pretreatment with morphine sulfate (MS) on electroencephalographic (EEG) manifestations of seizures due to bicuculline (BIC) were studied in freely moving rats. Electrodes were placed on frontal and occipital cortices, into the hippocampus and into a region of the prepiriform cortex, area tempe...

    journal_title:Epilepsy research

    pub_type: 杂志文章

    doi:10.1016/0920-1211(89)90012-0

    authors: Massotti M,Gale K

    更新日期:1989-09-01 00:00:00

  • Sleep influences the intracerebral EEG pattern of focal cortical dysplasia.

    abstract:OBJECTIVE:Focal cortical dysplasia (FCD) is able to generate an intrinsic pathological EEG activity characterized by a continuous or near-continuous spiking. Different patterns of discharge were described. We examined quantitatively the distribution of the intracerebral FCD patterns in relation to sleep in order to inv...

    journal_title:Epilepsy research

    pub_type: 杂志文章

    doi:10.1016/j.eplepsyres.2015.03.014

    authors: Menezes Cordeiro I,von Ellenrieder N,Zazubovits N,Dubeau F,Gotman J,Frauscher B

    更新日期:2015-07-01 00:00:00

  • The applications of time-frequency analyses to ictal magnetoencephalography in neocortical epilepsy.

    abstract:PURPOSE:Ictal magenetoencephalographic (MEG) discharges convey significant information about ictal onset and propagation, but there is no established method for analyzing ictal MEG. This study sought to clarify the usefulness of time-frequency analyses using short-time Fourier transform (STFT) for ictal onset and propa...

    journal_title:Epilepsy research

    pub_type: 杂志文章

    doi:10.1016/j.eplepsyres.2010.05.001

    authors: Yagyu K,Takeuchi F,Shiraishi H,Nakane S,Sueda K,Asahina N,Kohsaka S,Umeoka S,Usui N,Baba K,Saitoh S

    更新日期:2010-08-01 00:00:00

  • Self-limited epilepsy with centro-temporal spikes: A study of 46 patients with unusual clinical manifestations.

    abstract:PURPOSE:We retrospectively analyzed the seizure characteristics, EEG pattern, treatment, and outcome in a series of patients with self-limited epilepsy with centrotemporal spikes (SLECTS) who presented with unusual clinical manifestations. METHOD:A retrospective, descriptive, multicenter study was conducted evaluating...

    journal_title:Epilepsy research

    pub_type: 杂志文章

    doi:10.1016/j.eplepsyres.2020.106507

    authors: Galicchio S,Espeche A,Cersosimo R,Chacon S,Gamboni B,Adi J,Fasulo L,Semprino M,Fortini S,Cachia P,Caraballo RH

    更新日期:2021-01-01 00:00:00

  • Effects of AWD 140-190 on stimulus-induced field potentials and on different patterns of epileptiform activity induced by low calcium or low magnesium in rat entorhinal cortex hippocampal slices.

    abstract::AWD 140-190 a potent new anticonvulsant was tested on several types of epileptiform activities in entorhinal cortex hippocampal slices. AWD 140-190 suppressed completely and in a dose-dependent manner spontaneous seizure-like events induced by lowering extracellular Ca2+. In the low magnesium model, AWD 140-190 applie...

    journal_title:Epilepsy research

    pub_type: 杂志文章

    doi:10.1016/s0920-1211(97)00066-1

    authors: Armand V,Rundfeldt C,Heinemann U

    更新日期:1997-12-01 00:00:00

  • Chronic treatment with diazepam or the inverse benzodiazepine receptor agonist FG 7142 causes differential changes in the effects of GABA receptor stimulation.

    abstract::Daily treatment of mice with diazepam leads to the development of tolerance to the anxiolytic and anticonvulsant effect of the benzodiazepine, while daily treatment with the proconvulsant benzodiazepine receptor inverse agonist FG 7142 produces sensitization to its effects in that seizures develop (chemical kindling)....

    journal_title:Epilepsy research

    pub_type: 杂志文章

    doi:10.1016/0920-1211(88)90016-2

    authors: Löscher W,Stephens DN

    更新日期:1988-07-01 00:00:00

  • Familial pure paroxysmal kinesigenic dyskinesia in Han population from the Chinese mainland: a new subtype?

    abstract::Paroxysmal kinesigenic dyskinesia (PKD) is a rare neurologic inherited disease with heterogeneity. Autosomal dominant (AD) is the common inherited mode. There have been two loci mapped to 16 chromosome for PKD. However, no gene responsible for it has been identified so far. We collected 6 pedigrees from Chinese mainla...

    journal_title:Epilepsy research

    pub_type: 杂志文章

    doi:10.1016/j.eplepsyres.2008.04.012

    authors: Zhou J,Li G,Chen C,Liu D,Xiao B

    更新日期:2008-08-01 00:00:00

  • Cardiac changes in epileptic baboons with high-frequency microburst VNS therapy: A pilot study.

    abstract::The epileptic baboon provides a natural model of idiopathic generalized epilepsy and sudden unexpected death in epilepsy (SUDEP). We sought to evaluate autonomic differences, including heart rate (HR), heart rate variability (HRV) and corrected QT-duration (QTc) between two epileptic (EB1, EB2) and one control (CB) ba...

    journal_title:Epilepsy research

    pub_type: 杂志文章

    doi:10.1016/j.eplepsyres.2019.106156

    authors: de la Garza MA,Poldiak D,Shade R,Salinas FS,Papanastassiou AM,Szabó CÁ

    更新日期:2019-09-01 00:00:00

  • Interictal SPECT of rCBF is of clinical utility in the preoperative evaluation of patients with partial epilepsy.

    abstract::Fifty-eight patients with drug-resistant partial epilepsy were studied preoperatively by interictal rCBF measurements using 99mTc-HMPAO and a dedicated brain SPECT camera (Tomomatic 64). Follow-up of seizure outcome, using the "Engel score", was at least 3 years. The data were analyzed in a blinded set-up, first visua...

    journal_title:Epilepsy research

    pub_type: 杂志文章

    doi:10.1016/0920-1211(96)00018-6

    authors: Andersen AR,Hansen BA,Høgenhaven H,Herning M,Paulson O,Dam M

    更新日期:1996-09-01 00:00:00

  • Brief asymmetric tonic posturing with diffuse low-voltage fast activity in seizures arising from the mesial parietal region.

    abstract:AIM:Seizures originating from the parietal lobe can demonstrate variable semiology. Our aim was to describe the electroclinical features of seizures originating from the mesial parietal lobe. METHOD:We identified four patients through the Comprehensive Epilepsy Program at our institution, who had strong evidence of a ...

    journal_title:Epilepsy research

    pub_type: 杂志文章

    doi:10.1016/j.eplepsyres.2014.09.011

    authors: Khan SA,Carney PW,Archer JS

    更新日期:2014-12-01 00:00:00