Abstract:
:The compound 5-(4-chlorophenyl)-2,4-dihydro-4-ethyl-3H-1,2,4-triazol-3-one (MDL 27,192) was evaluated in a variety of rodent models to assess its anticonvulsant profile and its potential neuroprotective activity. MDL 27,192 demonstrated anticonvulsant activity in a wide range of epilepsy models that are genetically-based (audiogenic seizures in the seizure susceptible DBA/2J or Frings mouse; spike wave seizures in genetic absence epilepsy rats of Strasbourg (GAERS), electrically-based (MES seizures in mice and rats, corneally-kindled seizures in rats) and chemically-based (bicuculline, PTZ, picrotoxin, 3-mercaptopropionic acid, quinolinic acid and strychnine). When compared to valproate, orally administered MDL 27,192 was 17-48-fold more potent as an anticonvulsant and showed a safety index one to three-fold greater. Following a timed intravenous administration of PTZ to mice, MDL 27,192, but not phenytoin or carbamazepine, consistently increased the latencies to first twitch and clonus. MDL 27,192 was active in a genetic model of absence epilepsy, the GAERS rat model. These data indicate that MDL 27,192 likely exerts its anticonvulsant action by affecting seizure spread and by raising seizure threshold. MDL 27,192 did not display any signs of tolerance following subchronic (15 day) administration. In tests of neuroprotective potential, MDL 27,192 reduced infarct volume in a permanent middle cerebral artery occlusion model of focal cerebral ischemia in rats and reduced the loss of hippocampal dentate hilar neurons in an animal model of unilateral head injury. In summary, MDL 27,192 possesses a broad-spectrum anticonvulsant profile. The potential for reduced tolerance and neuroprotective activity are additional positive features of MDL 27,192's preclinical profile.
journal_name
Epilepsy Resjournal_title
Epilepsy researchauthors
Kehne JH,Kane JM,Chaney SF,Hurst G,McCloskey TC,Petty MA,Senyah Y,Wolf HH,Zobrist R,White HSdoi
10.1016/s0920-1211(96)01020-0subject
Has Abstractpub_date
1997-04-01 00:00:00pages
41-54issue
1eissn
0920-1211issn
1872-6844pii
S0920-1211(96)01020-0journal_volume
27pub_type
杂志文章abstract::The experimental antiepileptic drug, levetiracetam (UCB L059), a piracetam analogue has been investigated in photosensitive patients in the "photosensitivity model", an early phase II study. A total of 12 patients (10 females, 2 males) with a mean age of 21.5 years (range 13-38) were investigated during a 3 day period...
journal_title:Epilepsy research
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1016/s0920-1211(96)00031-9
更新日期:1996-11-01 00:00:00
abstract::Treatment of epileptic patients with valproic acid (VPA) may be associated with substantial weight changes that may increase morbidity and impair adherence to the treatment regimen. VPA-induced weight gain seems to be associated with many metabolic disturbances; the most frequent are hyperinsulinemia and insulin resis...
journal_title:Epilepsy research
pub_type: 杂志文章,评审
doi:10.1016/j.eplepsyres.2013.08.016
更新日期:2013-11-01 00:00:00
abstract::Pharmacoresistant mesial temporal lobe epilepsy (mTLE) represents the major indication for epilepsy surgery. Since epilepsy surgery is an elective treatment option, preserving cognition is a high priority. Given the essential role of temporomesial structures in declarative long-term memory formation, surgical treatmen...
journal_title:Epilepsy research
pub_type: 杂志文章,评审
doi:10.1016/j.eplepsyres.2017.08.017
更新日期:2018-05-01 00:00:00
abstract:AIM:To investigate biochemical cardiovascular risk factors and vascular endothelial function and structure in children with epilepsy on antiepileptic drugs (AEDs), particularly sodium valproate (VPA) and carbamazepine (CBZ). BACKGROUND:Individuals with epilepsy have increased risk factors for vascular disease, particu...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2014.04.006
更新日期:2014-08-01 00:00:00
abstract::Early Onset Absence Epilepsy constitutes an Idiopathic Generalized Epilepsy with absences starting before the age of four years. Mutations in SLC2A1, encoding the glucose transporter, account for approximately 10% of EOAE cases. The role of SLC2A1 mutations in absence epilepsies with a later onset has not been assesse...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2012.11.004
更新日期:2013-07-01 00:00:00
abstract:OBJECTIVE:To describe the use of a population pharmacokinetic (PopPK) model incorporating weight and ontogeny to identify effective clobazam (CLB) dosing for use in a clinical trial in pediatric patients with Dravet syndrome. METHODS:Pharmacokinetic data were combined from 3 CLB trials (OV-1012, OV-1017, and study 301...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2019.106182
更新日期:2019-11-01 00:00:00
abstract::Binding of valproate and palmitate to serum albumin was studied in 29 valproate-treated epileptic patients. The results were compared with similar observations in a reference group of 43 non valproate-treated individuals. The binding affinity for palmitate was decreased (P < 0.0001) resulting in increased availability...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/0920-1211(93)90040-e
更新日期:1993-09-01 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::Results of previous studies suggested that the brainstem participates in amygdaloid (AM) kindled seizure generalization and the positive transfer effect at the secondary site AM. This study was undertaken to define the role of the brainstem in the patterning of AM kindling, the maintenance of AM kindled seizure and th...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/s0920-1211(97)00068-5
更新日期:1998-01-01 00:00:00
abstract::In a selected group of temporal lobe epilepsy patients with seizures refractory to pharmacological treatment, pharmacological seizure control can be attained by surgical resection of the epileptic zone. We investigated to what extent pharmaco-resistance is reflected in a reduced response at the cellular level, in neur...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/s0920-1211(98)00061-8
更新日期:1998-09-01 00:00:00
abstract::Children with epilepsy face significant cognitive and behavioral impairments. These impairments are due to a poorly characterized interaction between the underlying etiology, the effect of seizures and the effect of medication. The large variation in these factors make understanding the main drivers of cognitive impai...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2014.11.005
更新日期:2015-02-01 00:00:00
abstract::The present study aimed at investigating to what extent the regulation of excitability in cortical networks, as indicated by surface-negative slow cortical potentials (SCPs), is impaired in epileptic patients and to what extent training of SCP self-regulation by means of biofeedback and instrumental learning procedure...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/0920-1211(93)90075-i
更新日期:1993-01-01 00:00:00
abstract::The present study used Nissl stains and glutamate decarboxylase immunoreactivity (GAD-IR) to quantify the acute and chronic toxicity of kainic acid (KA) on focal and remote hippocampal principal neurons (i.e., pyramidal and granule cells) and on putative inhibitory neurons (GAD-IR or GABAergic) following intrahippocam...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/0920-1211(90)90063-2
更新日期:1990-01-01 00:00:00
abstract::A role of cholinergic nervous system in the behavioral impairments induced by repeated ECS is not understood. The α4β2 nicotinic acetylcholine receptor (nAChR) agonist ABT-418, but not the α7 nAChR agonist, significantly ameliorated the impairment of spontaneous alternation behavior in the Y-maze test. And, repeated E...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2012.09.017
更新日期:2013-03-01 00:00:00
abstract:PURPOSE:We sought to systematically review and perform a meta-analysis of the magnetic resonance spectroscopy (MRS) findings regarding juvenile myoclonic epilepsy (JME). METHODS:We searched for studies in the PubMed, Web of Science, and Embase electronic databases. Two authors collected articles and extracted data ind...
journal_title:Epilepsy research
pub_type: 杂志文章,meta分析,评审
doi:10.1016/j.eplepsyres.2016.01.004
更新日期:2016-03-01 00:00:00
abstract:PURPOSE:To describe the clinical findings in a family with a benign form of mesial temporal lobe epilepsy and to identify the causative genetic factors. METHODS:All participants were personally interviewed and underwent neurologic examination. The affected subjects underwent EEG and most of them neuroradiological exam...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2013.11.002
更新日期:2014-02-01 00:00:00
abstract::Spreading depression (SD), a self-propagating wave of reversible cellular depolarization, is thought to play an important role in brain pathophysiology. SD and seizures are closely related events but little is known about involvement of SD in chronic epileptogenesis. Here we show that cortical SD is the first and high...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2006.05.014
更新日期:2006-09-01 00:00:00
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
更新日期:1994-10-01 00:00:00
abstract:BACKGROUND:Diffusion tensor tractography of the anterior extent of the optic radiation - Meyer's loop - prior to temporal lobe resection (TLR) may reduce the risk for postoperative visual field defect. Currently there is no standardized way to perform tractography. OBJECTIVE:To visualize Meyer's loop using determinist...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2014.01.017
更新日期:2014-03-01 00:00:00
abstract:PURPOSE:In patients with left temporal lobe epilepsy (TLE) due to hippocampal sclerosis (HS) decreased naming ability is common, suggesting a critical role for the medial left temporal lobe in this task. We investigated the integrity of language networks with functional MRI (fMRI) in controls and TLE patients. EXPERIM...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2011.04.007
更新日期:2011-08-01 00:00:00
abstract::The subjects were 106 SMIDS with epilepsy. They were classified into four epileptic syndromes: (1) SE-MISF (34.0%), (2) SGE (25.5%), (3) SLRE (20.7%), and (4) epileptic discharge-free patients (EDFP) (19.8%). Clinical electroencephalographic studies elucidated the following result: (1) The seizure disappearance rate w...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2007.09.006
更新日期:2007-12-01 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: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::The effect of magnesium-free medium on electrical and CaM kinase II activity in the rat hippocampal slice was examined. Experimental slices were incubated in 2 mM Mg, then exposed to magnesium-free medium for 1 h. Control slices were concurrently run in 2 mM Mg. Slices were then frozen and CaM kinase II activity was m...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/0920-1211(91)90054-j
更新日期:1991-09-01 00:00:00
abstract::Interpreting electrocorticography (ECoG) in the context of neuroimaging requires that multimodal information be integrated accurately. However, the implantation of ECoG electrodes can shift the brain impacting the spatial interpretation of electrode locations in the context of pre-implant imaging. We characterized the...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2020.106410
更新日期:2020-11-01 00:00:00
abstract:PURPOSE:To compare and validate the gradient magnetic-field topography (GMFT) method of current source localization for understanding epileptic zones against equivalent current dipole (ECD) and intracranial video-EEG (IVEEG) data in patients with intractable neocortical epilepsy. METHODS:We used retrospective data fro...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2010.04.002
更新日期:2010-06-01 00:00:00
abstract::A randomised, double-blind, placebo-controlled crossover study of add-on remacemide hydrochloride was carried out in epilepsy patients being treated with phenytoin (PHT) monotherapy. Eleven patients were recruited, ten of whom completed the study. Plasma concentration profiles of PHT, remacemide, and its active desgly...
journal_title:Epilepsy research
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/s0920-1211(96)01005-4
更新日期:1997-01-01 00:00:00
abstract:OBJECTIVE:The aim of this study was to investigate whether there may be a correlation between the anatomical variants of Circle of Willis (CoW) and presence/laterality of mesial temporal sclerosis (MTS). METHODS:We retrospectively identified the CoW variants on Wada angiograms in 71 patients with pathologically proven...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2017.02.017
更新日期:2017-05-01 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:PURPOSE:To evaluate if the duration of epilepsy influences MRI volumes of the hippocampus, amygdala, parahippocampal gyrus, entorhinal cortex and temporal pole of both hemispheres and epileptogenic hippocampus neuronal cell density and dentate gyrus granular cells distribution in patients with refractory mesial tempora...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2018.08.009
更新日期:2018-11-01 00:00:00