Abstract：
:An earlier pharmacodynamic study of the chiral antiepileptic drug stiripentol in an intravenous pentylenetetrazol-induced seizure model in the rat showed the development of a significant degree of tolerance to the anticonvulsant and neurotoxic effects following subacute treatment with the racemic compound. A more recent study with the pure enantiomers of stiripentol indicated that the (+)-enantiomer is 2.4 times more potent than the (-)-enantiomer, based on a comparison of brain EC50 values for the anticonvulsant effect. Moreover, (-)-stiripentol has a much longer elimination half-life than (+)-stiripentol. We have re-analyzed the brain and blood samples from the first pharmacodynamic study using a newly developed chiral HPLC assay to investigate whether the tolerance phenomenon with racemic stiripentol was due to a shift in the enantiomeric composition of stiripentol in brain tissue during repetitive administration of racemic drug. A large increase, as much as 5-6-fold, in the (-)/(+) ratio in brain concentration of stiripentol was observed after subacute administration, as compared with that after a single dose of the racemic drug. The enrichment in the less potent enantiomers during repetitive drug administration explains the previous observation of an apparent development of tolerance when the pharmacologic effects were related to total [(-)+(+)] brain concentrations of stiripentol as measured by a non-stereoselective assay. The results of this study highlight the importance of stereoselective pharmacokinetics in investigating the pharmacodynamics of the racemic mixture of a chiral anticonvulsant.
journal_name
Epilepsy Resjournal_title
Epilepsy researchauthors
Arends RH,Zhang K,Levy RH,Baillie TA,Shen DDdoi
10.1016/0920-1211(94)90001-9subject
Has Abstractpub_date
1994-06-01 00:00:00pages
91-6issue
2eissn
0920-1211issn
1872-6844pii
0920-1211(94)90001-9journal_volume
18pub_type
杂志文章abstract：PURPOSE:To determine the feasibility of using epileptiform events detected by continuous electrocorticographic monitoring via a brain-responsive neurostimulation system to supplement patient-maintained seizure diaries. METHODS:Data were retrospectively analyzed from a randomized controlled trial of brain-responsive ne...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/j.eplepsyres.2020.106302
更新日期：2020-03-01 00:00:00
abstract：PURPOSE:Cryptogenic focal epilepsy (CFE) is a heterogeneous clinical disorder including patients with severe refractory forms and patients with a fairly good prognosis. Predictors of prognosis in CFE are poorly understood. The aim of this retrospective study is to identify long-term (5-year) prognostic predictors in pa...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/j.eplepsyres.2013.07.004
更新日期：2013-11-01 00:00:00
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
更新日期：2021-01-01 00:00:00
abstract：:It has been established that febrile seizures and its extended syndromes like generalized epilepsy with febrile seizures (FS) plus (GEFS+) and Dravet syndrome have been associated with mutations especially in SCN1A and GABRG2 genes. In patients, the onset of FS is likely due to the combined effect of temperature and i...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/j.eplepsyres.2017.04.020
更新日期：2017-08-01 00:00:00
abstract：:We analyzed preoperative ictal SPECT results from 18 frontal lobe epilepsy patients who underwent epilepsy surgery (mean age 22.9 years). Seizure onset at implanted subdural electrodes was defined as the epileptic focus in 16 of 18 patients. In two additional patients, the resected area on postoperative magnetic reson...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/j.eplepsyres.2005.09.032
更新日期：2006-02-01 00:00:00
abstract：PURPOSE:To analyze electroclinical features of absence seizures during sleep. PRINCIPAL RESULTS:30 children with genetic generalized epilepsy had 52 paroxysms of GSW >2s during sleep. 18/52 (35%) demonstrated a clinical sign. Ictal GSW lasted an average of 6.5s. CONCLUSION:Motor manifestations are seen during GSW>2s ...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/j.eplepsyres.2010.12.009
更新日期：2011-02-01 00:00:00
abstract：INTRODUCTION:Juvenile myoclonic epilepsy (JME) is a genetic generalized epilepsy syndrome. Under appropriate antiepileptic drugs (AED) up to 85% of patients become seizure-free, but many may have a relapse after AED withdrawal. METHODS:We retrospectively studied 242 patients with JME at the Department of Neurology, Me...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/j.eplepsyres.2014.09.008
更新日期：2014-12-01 00:00:00
abstract：PURPOSE:The intracarotid amytal test is commonly used as a predictor of memory dysfunctioning after anterior temporal lobe resection (ATL) for intractable epilepsy. Asymmetry in memory scores can provide focus lateralizing information. In this study the predictive value of a set of Wada test parameters was analyzed, in...
journal_title：Epilepsy research
pub_type： 临床试验,杂志文章
doi：10.1016/s0920-1211(00)00097-8
更新日期：2000-05-01 00:00:00
abstract：BACKGROUND:GRIN-related developmental-epileptic encephalopathies are associated with a spectrum of neurodevelopmental disorders, including intellectual disability, epilepsy including continuous spike-and-wave during sleep syndrome (CSWS), or epilepsy-aphasia spectrum phenotypes such as in Landau-Kleffner syndrome. Effi...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/j.eplepsyres.2020.106325
更新日期：2020-07-01 00:00:00
abstract：:Fits of audiogenic seizures in rodents are considered as a model for generalized convulsive epilepsies in humans. The laminar distribution of the H3 histamine receptor binding densities was quantified in the motor cortex of two strains of rats with genetically determined generalized epilepsies, namely KM rats with aud...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/j.eplepsyres.2020.106543
更新日期：2020-12-25 00:00:00
abstract：:Aminergic signalling in the CNS is terminated by clearance of neurotransmitters from the synapse via high affinity transporter molecules in the presynaptic membrane. Relatively recent sequence identification of these molecules has now permitted the initiation of studies of regulation of transporter function at the cel...
journal_title：Epilepsy research
pub_type： 杂志文章,评审
doi：10.1016/s0920-1211(99)00072-8
更新日期：1999-12-01 00:00:00
abstract：:Depression is a frequent psychiatric symptom in epilepsy and has been related to epilepsy of temporal origin, especially of left-sided foci. No study differentiated the precise localization of the epileptogenic lesion within the temporal lobe. Regarding this issue, we evaluated depression assessed by the Beck Depressi...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/s0920-1211(99)00117-5
更新日期：2000-04-01 00:00:00
abstract：SUMMARY:Stereotactic radiofrequency amygdalohippocampectomy (AHE) has been reintroduced as an alternative treatment of mesial temporal lobe epilepsy. The aim of this study was to describe MRI changes after stereotactic AHE and to correlate the hippocampal and amygdalar volumes reduction with the clinical seizure outcom...
journal_title：Epilepsy research
pub_type： 临床试验,杂志文章
doi：10.1016/j.eplepsyres.2008.11.013
更新日期：2009-02-01 00:00:00
abstract：:Periventricular nodular heterotopia (PVNH) is a neuronal migrational disorder often associated with pharmacoresistant epilepsy (PRE). Resective surgery for PVNH is limited by its deep location, and the overlying eloquent cortex or white matter. Stereotactic MR guided laser interstitial thermal therapy (MRgLITT) has re...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/j.eplepsyres.2014.01.009
更新日期：2014-03-01 00:00:00
abstract：PURPOSE:This study aimed to evaluate the carotid artery intima-media thickness (CA-IMT) in adult patients with epilepsy and its contribution to oxidative stress and vascular risk biomarkers. METHODS:This study included 225 adult epileptic and 60 control subjects. For all, CA-IMT, fasting lipid profile (TC, TG, HDL-c a...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/j.eplepsyres.2007.03.010
更新日期：2007-05-01 00:00:00
abstract：:The KCNAB1 gene is a candidate susceptibility factor for lateral temporal epilepsy (LTE) because of its functional interaction with LGI1, the gene responsible for the autosomal dominant form of LTE. We investigated association between polymorphic variants across the KCNAB1 gene and LTE. The allele and genotype frequen...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/j.eplepsyres.2011.01.010
更新日期：2011-03-01 00:00:00
abstract：:Previous investigations in seizure-prone mice have suggested that an abnormally elevated production of the astrocyte-derived neuroexcitant, quinolinic acid (QUIN), plays a role in seizure susceptibility. In order to evaluate further the role of QUIN metabolism in genetic murine seizure models, the activities of its bi...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/0920-1211(94)90039-6
更新日期：1994-07-01 00:00:00
abstract：PURPOSE:Cases of temporal lobe epilepsy (TLE) with ipsilateral amygdala enlargement (AE) have increasingly been reported. However, the white matter (WM) abnormalities of TLE patients with AE remain poorly investigated. Here we explored macrostructural and microstructural WM abnormalities in TLE patients with AE compare...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/j.eplepsyres.2016.09.011
更新日期：2016-11-01 00:00:00
abstract：:Basal and high potassium-stimulated release of endogenous amino acids was measured using brain dialysis in the hippocampus of urethane-anesthetized seizure-resistant (SR) and seizure-susceptible (SS) rats. Moreover, the tissue level of amino acids was determined in the hippocampus, sensorimotor cortex, cerebellum and ...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/0920-1211(89)90040-5
更新日期：1989-03-01 00:00:00
abstract：:The deletion of a sodium channel gene cluster located on chromosome 2q24.3 is associated with variable epilepsy phenotypes, including Dravet syndrome and migrating partial seizures of infancy. Although SCN1A is considered as the major contributor to the epilepsy phenotype, the role of other sodium channel genes that m...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/j.eplepsyres.2014.10.008
更新日期：2015-01-01 00:00:00
abstract：:This investigation of cognitive functioning in patients with symptomatic localization-related (partial) epilepsy prior to administration of antiepileptic medication is part of a nationwide prospective, double-blind study of drug efficacy and longitudinal changes in cognition associated with seizure disorders. Recently...
journal_title：Epilepsy research
pub_type： 临床试验,杂志文章,多中心研究
doi：10.1016/s0920-1211(97)00091-0
更新日期：1998-03-01 00:00:00
abstract：OBJECTIVE:Despite increasing amounts of research on periodic discharges (PDs), large clinical studies regarding their prognostic value are lacking. The aim of the current study was to evaluate the clinical implications and prognostic value of PDs. METHODS:In this single-center retrospective cohort study, we included p...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/j.eplepsyres.2017.02.004
更新日期：2017-03-01 00:00:00
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
更新日期：2005-08-01 00:00:00
abstract：PURPOSE:Pyridoxine-dependent epilepsy (PDE) is a rare autosomal recessive disorder caused by mutations of the ALDH7A1 gene. We aimed to analyze the relations between the clinical diagnosis and treatment of PDE and ALDH7A1 gene mutations in Chinese PDE patients. METHODS:The clinical manifestations, diagnosis and treatm...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/j.eplepsyres.2015.10.002
更新日期：2015-12-01 00:00:00
abstract：:The present study intends to identify factors that predict postoperative clinical outcome in patients with gangliogliomas (GG) and dysembryoplastic neuroepithelial tumors (DNT). We evaluated the medical records of 45 patients with GG and 13 patients with DNT, treated surgically between 1985 and 1995. We assessed sever...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/s0920-1211(00)00208-4
更新日期：2001-03-01 00:00:00
abstract：PURPOSE:Indoleamine 2,3-dioxygenase (IDO) is a cytokine-inducible enzyme that participates in tryptophan (trp) and serotonin metabolism with an ability to modulate neuroinflammation. Several recent studies have shown associations between cytokines and epilepsy. In this study we investigated whether activation of IDO is...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/j.eplepsyres.2011.02.003
更新日期：2011-05-01 00:00:00
abstract：:Activation of group I metabotropic glutamate receptors (mGluRs) produces a long-lasting change in hippocampal excitability that persists in the absence of an agonist. Exposure to the group I mGluR agonist dihydroxyphenylglycine (DHPG) results in the induction of spontaneously occurring epileptiform activity in the CA3...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/j.eplepsyres.2008.04.005
更新日期：2008-09-01 00:00:00
abstract：PURPOSE:To characterize gabapentin pharmacokinetics in infants and children using a population approach and to identify important demographic and/or physiologic determinants of gabapentin disposition. METHODS:Gabapentin was administered in single doses of 10 mg/kg (N=48 healthy subjects, age 1 month-12 years) or in mu...
journal_title：Epilepsy research
pub_type： 临床试验,杂志文章
doi：10.1016/s0920-1211(01)00311-4
更新日期：2001-12-01 00:00:00
abstract：:The effects of GABA uptake inhibitors, SKF 89976A and SKF 100330A, on recurrent inhibition were studied in the rat hippocampal slice preparation by the antidromic-orthodromic stimulation test. Population spikes evoked orthodromically by stimulation of the stratum radiatum and recorded in the CA1 pyramidal cell body la...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/0920-1211(93)90026-4
更新日期：1993-10-01 00:00:00
abstract：PURPOSE:We studied the effect of fosphenytoin (FOS) pre-medication on the incidence and thresholds of after-discharges (ADs), seizures, and functional responses during electrical stimulation mapping (ESM). METHODS:As individualized by the attending epileptologist, FOS was given intravenously at 2 mg-phenytoin-equivale...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/j.eplepsyres.2018.01.017
更新日期：2018-02-01 00:00:00
