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 pipeline begins with the demonstration of activity in one or more animal screening models. Results from testing in a panel of such models provide a basis to differentiate agents and may offer clues as to the mechanism. Target activity may then be defined through cell-based studies, often years after the initial identification of activity. Some pipeline compounds are believed to act through conventional targets, whereas others are structurally novel and may act by novel mechanisms. Follow-on agents include the levetiracetam analogs brivaracetam and seletracetam that act as SV2A-ligands; the valproate-like agents valrocemide, valnoctamide, propylisopropyl acetamide, and isovaleramide; the felbamate analog flurofelbamate, a dicarbamate, and the unrelated carbamate RWJ-333369; the oxcarbazepine analog licarbazepine, which probably acts as a use-dependent sodium channel blockers, and its prodrug acetate BIA 2-093; various selective partial benzodiazepine receptor agonists, including ELB139, which is a positive allosteric modulator of alpha3-containing GABA(A) receptors. A variety of AEDs that may act through novel targets are also in clinical development: lacosamide, a functionalized amino acid; talampanel, a 2,3-benzodiazepine selective noncompetitive AMPA receptor antagonist; NS1209, a competitive AMPA receptor antagonist; ganaxolone, a neuroactive steroid that acts as a positive modulator of GABA(A) receptors; retigabine, a KCNQ potassium channel opener with activity as a GABA(A) receptor positive modulator; the benzanilide KCNQ potassium channel opener ICA-27243 that is more selective than retigabine; and rufinamide, a triazole of unknown mechanism.
journal_name
Epilepsy Resjournal_title
Epilepsy researchauthors
Rogawski MAdoi
10.1016/j.eplepsyres.2006.02.004subject
Has Abstractpub_date
2006-06-01 00:00:00pages
273-94issue
3eissn
0920-1211issn
1872-6844pii
S0920-1211(06)00063-5journal_volume
69pub_type
杂志文章,评审abstract::Inflammatory mechanisms are involved in the pathogenesis of epilepsy. Vice versa, immune functions are regulated by the brain. We measured postictal changes in serum levels of the immuno-modulating cytokines IL-1beta, IL-6 and TNFalpha in patients with well-defined temporal lobe epilepsy (TLE) and determined modifying...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2009.05.009
更新日期:2009-09-01 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::Plasma total homocysteine (p-tHcy), serum folate (s-F), serum vitamin B-12 (s-B12) and plasma pyridoxal-5'-phosphate (p-PLP) were measured in epileptic children before and after a 20-week period of sodium valproate (group A, n=32) and carbamazepine (group B, n=20) monotherapy. P-tHcy significantly increased in both gr...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2006.06.015
更新日期:2006-10-01 00:00:00
abstract:AIM:Vitamin D (Vit D) has been considered as a neurosteroid and has a pivotal role in neuroprotection including epilepsy. Vit D regulator acts via a Vit D receptor (VDR). WAG/Rij rats have a genetically epileptic model of absence epilepsy with comorbidity of depression. The aim of the present study was to investigate t...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2019.106208
更新日期:2019-11-01 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::Here we describe a new non-human primate model of temporal lobe epilepsy (TLE) to better investigate the cause/effect relationships of human TLE. Status epilepticus (SE) was induced in adult marmosets by pilocarpine injection (250mg/kg; i.p.). The animals were divided in 2 groups: acute (8h post-SE) and chronic (3 and...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2011.04.015
更新日期:2011-09-01 00:00:00
abstract::Single photon emission computed tomography (SPECT) has frequently been used to investigate cerebral brain perfusion (CBP) occurring ictally and inter-ictally in epileptic patients. Several studies have addressed the multimodal analysis of the modifications occurring in cerebral areas involved in seizure activity, by c...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/s0920-1211(00)00111-x
更新日期:2000-06-01 00:00:00
abstract::Infantile spasms (IS) is a devastating epilepsy syndrome treated with adrenocorticotropic hormone (ACTH). To demonstrate the effects of adrenal dysfunction, adrenalectomy (ADX) and N-methyl-d-aspartate (NMDA)-induced rat model studies of IS were performed. The latency of the seizure in the ADX group decreased and the ...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2012.02.001
更新日期:2012-06-01 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 explore the association between patient-reported-outcomes measurements and costs in adult outpatients with drug refractory epilepsy (DRE) in Spain. METHODS:Secondary analysis of a cross-sectional study to determine resources utilization and related costs of refractory epilepsy in Spain (LINCE study). Cons...
journal_title:Epilepsy research
pub_type: 杂志文章,多中心研究
doi:10.1016/j.eplepsyres.2008.10.004
更新日期:2009-02-01 00:00:00
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....
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2003.12.007
更新日期:2004-02-01 00:00:00
abstract::Resting motor threshold (rMT) assessed by means of Transcranial Magnetic Stimulation (TMS) is thought to reflect trans-synaptic excitability of cortico-spinal neurons. TMS studies reporting rMT in idiopathic generalized epilepsies (IGEs) yielded discrepant results, so that it is difficult to draw a definitive conclusi...
journal_title:Epilepsy research
pub_type: 杂志文章,meta分析,评审
doi:10.1016/j.eplepsyres.2012.03.020
更新日期:2012-08-01 00:00:00
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
更新日期:1987-07-01 00:00:00
abstract::Previous experiments suggest the primary route of valproic acid (VPA) removal from the rabbit central nervous system (CNS) is by probenecid-sensitive transporters at the blood-brain barrier but not at the choroid plexus. The purpose of this study was to determine if other transport mechanisms at the choroid plexus pla...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/0920-1211(94)00075-8
更新日期:1995-03-01 00:00:00
abstract::We herein investigated risk factors of pediatric acute encephalopathy (AE) regarding the hitherto uncharacterized genetic background of seizure susceptibility underlying the pathogenesis of AE. The study included 15 patients with a history of various types of AE in childhood. We undertook the mutational analysis of th...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2010.07.005
更新日期:2010-10-01 00:00:00
abstract:OBJECT:The use of T2 relaxometry was investigated to detect non-sclerotic epileptogenic abnormality of the hippocampus in presurgical evaluation of temporal lobe epilepsy (TLE). METHODS:This prospective study included 30 patients who underwent hippocampectomy as part of surgical treatment of refractory TLE. Ten patien...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2016.06.001
更新日期:2016-10-01 00:00:00
abstract::In the immature brain the neurotransmitter γ-amino butyric acid (GABA) mediates a membrane depolarization and can contribute to both, inhibition and excitation. Therefore the consequences of a positive modulation of GABA(A) receptors by neurosteroids on epileptiform activity are hard to predict. In order to analyze wh...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2019.106196
更新日期:2019-11-01 00:00:00
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
更新日期:1996-05-01 00:00:00
abstract::Six anticonvulsant drugs, phenytoin (PHT), carbamazepine (CBZ), valproate (VPA), U-54494A, losigamone (LOS), and D-20443, were studied using rat hippocampal slices and standard electrophysiological techniques. The K+ channel blocker, 4-aminopyridine (4-AP), was used as neuronal stimulant. The extracellular parameters ...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/0920-1211(94)00077-a
更新日期:1995-02-01 00:00:00
abstract::This prospective study examined the effects of the new antiepileptic drug (AED) gabapentin (GBP) compared to the standard AED carbamazepine (CBZ) and placebo (PLA) on eye movements, posture and finger force control in 12 healthy volunteers who received single doses of 600 mg GBP and 400 mg CBZ in a placebo-controlled,...
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(98)00015-1
更新日期:1998-06-01 00:00:00
abstract::Opioid peptide release was monitored in the amygdala and hippocampus of freely moving rats following a single oral administration of gabapentin using microdialysis. Extracellular opioid peptide levels were elevated above basal levels in the amygdala within the first 60 (54%) and 90 min (68%) after gabapentin administr...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/s0920-1211(98)00121-1
更新日期:1999-05-01 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::Seizure forecasting would improve the quality of life of patients with refractory epilepsy. Although early findings were optimistic, no single feature has been found capable of individually characterizing brain dynamics during transition to seizure. Cross-frequency phase amplitude coupling has been recently proposed a...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2017.11.009
更新日期:2018-01-01 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:PURPOSE:To evaluate diffusion tensor imaging (DTI) indices of (i) cortical tubers and (ii) normal-appearing subcortical white matter adjacent to cortical tubers within the epileptogenic zone and non-epileptogenic zone. METHODS:Twelve children with tuberous sclerosis complex underwent MRI, DTI and magnetoencephalograph...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2010.01.008
更新日期:2010-05-01 00:00:00
abstract:BACKGROUND:Millions of individuals worldwide suffer from epilepsy, and up to 25% of patients have seizures that are resistant to currently available antiepileptic drugs. Hence, there continues to be a need for more seizure medications that are effective yet tolerable. Levodropropizine (LVDP) is an established antitussi...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2018.12.011
更新日期:2019-02-01 00:00:00
abstract::Multiple sclerosis (MS) patients are at higher risk for epilepsy. Epilepsy was frequent among our MS patients (6.55%). Progressive MS forms were associated with higher incidence of epilepsy (p=0.021). Partial motor seizures were observed in five patients (62.5%) and generalized tonic-clonic in three (37.5%). Electroen...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2009.01.009
更新日期:2009-04-01 00:00:00
abstract::To investigate involvement of extrafocal regions in mesial temporal lobe epilepsy (MTLE), we retrospectively explored abnormalities in distribution of iomazenil (IMZ) activity by identifying interhemispheric asymmetry on IMZ-SPECT images of patients with MTLE. Fourteen MTLE patients in whom a good surgical outcome was...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2012.07.001
更新日期:2013-02-01 00:00:00
abstract:OBJECTIVE:To study the pregnancy outcomes, including obstetric complications and fetal outcomes, in pregnant women with epilepsy (WWE) treated with direct brain-responsive neurostimulation (RNS System). METHODS:Retrospective review of obstetric outcomes and fetal outcomes in WWE treated with the RNS System at nine com...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2020.106532
更新日期:2021-01-01 00:00:00
abstract::Kindling, in the classical sense, involves progressively increasing responsivity to the intermittent repetition of the same 1-s subthreshold electrical stimulation over time, with the amygdala being the area most frequently studied. Such repeated subthreshold stimulation is associated with: lowering of the after-disch...
journal_title:Epilepsy research
pub_type: 杂志文章,评审
doi:10.1016/s0920-1211(02)00081-5
更新日期:2002-06-01 00:00:00