Abstract:
:CYP2C9 is mainly responsible for the metabolic clearance of phenytoin and (S)-warfarin. We have shown previously that mutations in the CYP2C9 gene are associated with diminished metabolism of (S)-warfarin, and so we have now studied the metabolism of phenytoin to its primary inactive metabolite, (S)-pHPPH, by these mutant enzymes. Kinetic parameters were determined for (S)-pHPPH formation using recombinant CYP2C9 variants purified from insect cells. The data demonstrate that the CYP2C9*3 gene product retains only 4-6% of the metabolic efficiency of the wild-type protein, CYP2C9*1, towards phenytoin and (S)-warfarin. Consequently, we suggest that homozygous expression of CYP2C9*3 may represent a common genetic basis for (apparently) idiosyncratic toxicities that have been reported for these two low therapeutic index drugs.
journal_name
Epilepsy Resjournal_title
Epilepsy researchauthors
Rettie AE,Haining RL,Bajpai M,Levy RHdoi
10.1016/s0920-1211(99)00017-0subject
Has Abstractpub_date
1999-07-01 00:00:00pages
253-5issue
3eissn
0920-1211issn
1872-6844pii
S0920121199000170journal_volume
35pub_type
杂志文章abstract:PURPOSE:Caffeine is a non-selective antagonist of A1 and A2A adenosine receptors (ARs). In this regard, nitric oxide (NO) is partly involved in the central effects of caffeine. In this study, we examined the effect of acute caffeine administration on pentylenetetrazole (PTZ)-induced seizure threshold by focusing on A1R...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2018.10.013
更新日期:2019-01-01 00:00:00
abstract:PURPOSE:Antiepileptic drugs (AEDs) may have adverse effects on bone metabolism and bone mineral density (BMD). The aim of this study is to determine the changes of bone metabolism and BMD in epilepsy patients who are undergoing levetiracetam (LEV) monotherapy. METHODS:Drug-naïve, sixty-one patients with recent onset e...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2012.09.002
更新日期:2013-03-01 00:00:00
abstract:PURPOSE:Focal cortical dysplasia (FCD) has been recognized as one of the most frequent causes of drug resistant epilepsy, especially in children. In infancy, onset of FCD-related epilepsy is substantially characterized by epileptic spasms (ES) or focal seizures. Which elements pertaining to the FCD are responsible for ...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2014.11.006
更新日期:2015-01-01 00:00:00
abstract::Brain glucose transport is dependent on glucose transporter 1 (GLUT1), encoded by the solute carrier family 2 member 1 (SLC2A1) gene. Mutations in SLC2A1 cause GLUT1 deficiency which is characterized by a broad spectrum of neurological phenotypes including generalized epilepsy, motor disorders, developmental delay and...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2017.04.007
更新日期:2017-07-01 00:00:00
abstract::Seizures that occur during early development are associated with adverse neurodevelopmental outcomes. Causation and mechanisms are currently under investigation. Induction of an early life seizure by kainic acid (KA) in immature rats on post-natal day (P) 7 results in behavioral changes in the adult rat that reflect s...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2020.106283
更新日期:2020-03-01 00:00:00
abstract:OBJECTIVE:This was the first proof of principle clinical trial assessing the efficacy and safety of rufinamide as adjunctive therapy in epileptic patients. The pharmacokinetic (PK) profile of rufinamide was also determined. METHODS:Fifty patients with diagnoses of partial or primary generalized tonic-clonic seizures w...
journal_title:Epilepsy research
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1016/s0920-1211(00)00185-6
更新日期:2001-02-01 00:00:00
abstract:BACKGROUND:Nuclear factor erythroid-2 related factor 2 (Nrf2) is a transcription factor, which activates the anti-oxidative stress response pathway. In epilepsy, oxidative stress is one of the key factors in the progression of the disease. So, the neuroprotective role of dimethyl fumarate (DMF), a Nrf2 pathway activato...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2018.02.011
更新日期:2018-07-01 00:00:00
abstract::To assess whether epileptic children have abnormal values of some trace elements, the aim of this preliminary study was to assess the serum zinc (Zn), copper (Cu), iron (Fe), and chromium (Cr) concentrations in 23 children with initial recognition of epilepsy before beginning of pharmacological therapy in comparison w...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2012.09.009
更新日期:2013-03-01 00:00:00
abstract::It has been suggested that loss of the astrocytic water channel aquaporin-4 (AQP4) from perivascular endfeet in sclerotic hippocampi contributes to increased seizure propensity in human mesial temporal lobe epilepsy (MTLE). Whether this loss occurs prior to or as a consequence of epilepsy development remains to be res...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2013.01.006
更新日期:2013-07-01 00:00:00
abstract::Benign childhood epilepsy with occipital paroxysms is classified among childhood benign partial epilepsies. The absence of neurological and neuropsychological deficits has long been considered as a prerequisite for a diagnosis of benign childhood partial epilepsy. Much evidence has been reported in literature in the l...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2005.03.004
更新日期:2005-05-01 00:00:00
abstract::The actions of adenosine in modulating amygdala kindling were examined using the stable adenosine analog 5'-N'-ethylcarboxamidoadenosine (NECA) and caffeine, an adenosine antagonist. Systemically administered NECA was found to significantly reduce the rate of postictal spiking and to significantly increase the duratio...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/0920-1211(90)90070-c
更新日期:1990-08-01 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::Mutations in GABRG2, which encodes the γ2 subunit of GABAA receptors, can cause both genetic epilepsy with febrile seizures plus (GEFS+) and Dravet syndrome. Most GABRG2 truncating mutations associated with Dravet syndrome result in premature termination codons (PTCs) and are stably translated into mutant proteins wit...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2013.12.005
更新日期:2014-03-01 00:00:00
abstract:PURPOSE:The aim of this study is to classify infantile cases with benign seizures into known epileptic syndromes, thereby facilitating discussion of clinical factors that could play an important role in diagnosis. SUBJECTS:Fifty-seven patients with afebrile seizures fulfilling all of the following criteria were enroll...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2006.02.007
更新日期:2006-08-01 00:00:00
abstract::A freezing probe was placed on the skull of postnatal day (PN) 1 rats to induce formation of a cerebrocortical microsulcus. Experimental studies were performed on PN days 21-24. At that time point, Nissl-stained sections revealed the presence of a microsulcus similar to that described in human dysplastic cortex. Immun...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/s0920-1211(98)00041-2
更新日期:1998-09-01 00:00:00
abstract:OBJECTIVE:To study potential delays in epilepsy surgery in children with drug-resistant epilepsy (DRE) of early-onset. METHODS:Medical records were reviewed from 87 children with DRE and seizure onset before age 3 years who underwent epilepsy surgery between 2006 and 2015. Information was obtained about each child's e...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2018.04.001
更新日期:2018-07-01 00:00:00
abstract::Glutamic acid decarboxylase autoantibodies (GADA) and anti-cardiolipin autoantibodies (ACA) have been detected in adult subjects with epilepsy, though the functional implications of these findings are a matter of debate. This study aimed to determine the prevalence of GADA and ACA and to investigate their clinical sig...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2013.02.009
更新日期:2013-07-01 00:00:00
abstract::The prevailing understanding of generalized epilepsy is shaped by the traditional definition that "the responsible neuronal discharge takes place, if not throughout the entire grey matter, then at least in the greater part of it and simultaneously on both sides". This view is no longer tenable since concurrent finding...
journal_title:Epilepsy research
pub_type: 杂志文章,评审
doi:10.1016/j.eplepsyres.2015.04.008
更新日期:2015-08-01 00:00:00
abstract::The effects of a novel anticonvulsant, zonisamide (3-sulfamoylmethyl-1,2-benzisoxazole), on photically induced seizures were studied in the lateral geniculate-kindled cat. Zonisamide was found to reduce the behavioral severity of seizure responses to photic stimulation in a dose-related manner. This anticonvulsant eff...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/0920-1211(90)90096-e
更新日期:1990-11-01 00:00:00
abstract::Lithium is still the mainstay in the treatment of affective disorders as a mood stabilizer. Lithium also shows some anticonvulsant properties. While the underlying mechanisms of action of lithium are not yet exactly understood, we used a model of clonic seizure induced by pentylenetetrazole (PTZ) in male NMRI mice to ...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2010.02.001
更新日期:2010-05-01 00:00:00
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
更新日期:1988-07-01 00:00:00
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
更新日期:2006-02-01 00:00:00
abstract::The new antiepileptic drug zonisamide was evaluated in a European multicenter parallel-group double-blind trial as add-on treatment for 139 patients with refractory partial epilepsy. During treatment with zonisamide complex partial seizures decreased by 27.7% compared to placebo (P < 0.05) and the median rate dropped ...
journal_title:Epilepsy research
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/0920-1211(93)90011-u
更新日期:1993-05-01 00:00:00
abstract::There is a remarkable array of new chemical entities in the current antiepileptic drug (AED) development pipeline. In some cases, the compounds were synthesized in an attempt improve upon the activity of marketed AEDs. In other cases, the discovery of antiepileptic potential was largely serendipitous. Entry into the p...
journal_title:Epilepsy research
pub_type: 杂志文章,评审
doi:10.1016/j.eplepsyres.2006.02.004
更新日期:2006-06-01 00:00:00
abstract:PURPOSE:To study the extent and characteristics of dietary and herbal supplements use in a large cohort of adult patients with epilepsy. METHODS:This prospective study included 490 patients receiving care at a university epilepsy clinic. A number of variables, including demographics, characteristics of epilepsy and it...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2019.106168
更新日期:2019-10-01 00:00:00
abstract::Tiagabine is a novel antiepileptic drug which has clinical efficacy against complex refractory and myoclonic seizures. The anticonvulsant mechanism of action of tiagabine results from its blockade of neuronal and glial GABA-uptake, thereby increasing GABA levels in the synaptic cleft. Here we present a comparison of t...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/s0920-1211(97)00031-4
更新日期:1997-07-01 00:00:00
abstract:OBJECTIVE:To assess functional organization of the motor cortex in patients with Unverricht-Lundborg disease (EPM1A) using a combined neurophysiologic and imaging approach. METHODS:EPM1A patients underwent transcranial magnetic stimulation (TMS)-based cortical mapping of the motor hand area. Moreover, they performed n...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2020.106278
更新日期:2020-02-01 00:00:00
abstract:BACKGROUND:Since intracranial electrode implantation has limited spatial sampling and carries significant risk, placement has to be effective and efficient. Structural and functional imaging of several different modalities contributes to localising the seizure onset zone (SoZ) and eloquent cortex. There is a need to su...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2013.08.002
更新日期:2013-11-01 00:00:00
abstract::The present study examined whether the perceived behavioral problems of children with idiopathic epilepsy differed from those of healthy controls according to parent proxy-reports and which factors are associated with these problems. The parents of 106 children with idiopathic epilepsy and 305 healthy controls aged 6-...
journal_title:Epilepsy research
pub_type: 杂志文章,多中心研究
doi:10.1016/j.eplepsyres.2012.01.014
更新日期:2012-06-01 00:00:00
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 rece...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/0920-1211(94)90001-9
更新日期:1994-06-01 00:00:00