Abstract:
:The novel anticonvulsant, remacemide HCl [(+/-)-2-amino-N-(1-methyl-1,2-diphenylethyl)acetamide monohydrochloride; FPL12924AA], and a desglycinated metabolite [(+/-)-1-methyl-1,2-diphenylethylamine monohydrochloride; FPL 12495AA] reversibly limited sustained high-frequency repetitive firing (SRF) of sodium-dependent action potentials by mouse spinal cord neurons in monolayer dissociated cell culture. Limitation occurred with an IC50 of 7.9 X 10(-6) M for remacemide and 1.2 X 10(-6) M for FPL 12495AA (P < 0.05 vs. remacemide). Stereoisomers of the desglycinate limited SRF with IC50 values of 3.3 X 10(-6) M and 3.5 X 10(-6) M for the S(+) and R(-) compounds, respectively. The concentration of racemic desglycinate and of either stereoisomer that produced limitation in all neurons tested was 10(-4) M. Maximal rate of rise (Vmax) of action potentials decreased progressively until firing ceased during 400-ms depolarizing pulses. Efficacy of remacemide, but not of the desglycinate, increased with time (maximum at 16-36 h). The limitation was voltage dependent. In addition, reduction of Vmax and action potential failure occurred during stimulation with 400-ms pulses and trains of brief (1 ms) depolarizations at different frequencies. These findings suggest an effect on voltage-sensitive sodium current that generates the action potential upstroke. Remacemide and the desglycinate also significantly reduced the amplitude of neuronal responses to pressure application of NMDA in use-dependent manner at concentrations equal to the IC50 values for limitation of action potential firing. Resting potential and input resistance were not changed significantly by either drug. Limitation of high-frequency firing of action potentials by both remacemide HCl and FPL 12495AA may contribute to the anticonvulsant efficacy of these compounds at concentrations overlapping the range required to block glutamatergic hyperexcitability.
journal_name
Epilepsy Resjournal_title
Epilepsy researchauthors
Wamil AW,Cheung H,Harris EW,McLean MJdoi
10.1016/0920-1211(95)00053-4subject
Has Abstractpub_date
1996-02-01 00:00:00pages
1-14issue
1eissn
0920-1211issn
1872-6844pii
0920121195000534journal_volume
23pub_type
杂志文章abstract::The ketogenic diet (KD) increased the expression of calbindin-D(28k) (CB) in the interneurons of the hippocampus compared with the normal diet (ND)-fed mice. Also, 2 days after kainic acid (KA) administration, numerous CB-expressing astrocytes were found in the KD-fed mice compared with those of the ND-fed mice. These...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2005.05.008
更新日期:2005-07-01 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::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::The purpose of the study was to evaluate the efficacy and safety of topiramate (TPM) as adjunctive therapy in children, adolescents and young adults with Lennox-Gastaut syndrome (LGS). We performed a prospective open label add-on study in 45 patients (age 4-34 years, mean 15.9 years) with LGS and refractory seizures. ...
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(02)00103-1
更新日期:2002-09-01 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:BACKGROUND:Idiopathic epilepsy (IE) is a syndrome that comprises epilepsy only, with no underlying structural brain lesion or other neurological signs or symptoms. Numerous studies have shown that genetic factors play an important role in IE. IE is a common disease in the Chinese Han population. However, the genetic ep...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2011.09.013
更新日期:2012-02-01 00:00:00
abstract:PURPOSE:Epilepsy is a diverse neurological condition with extreme genetic and phenotypic heterogeneity. The introduction of next-generation sequencing into the clinical laboratory has made it possible to investigate hundreds of associated genes simultaneously for a patient, even in the absence of a clearly defined synd...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2018.05.004
更新日期:2018-08-01 00:00:00
abstract::Interictal blood flow single photon emission computed tomography (SPECT) has been considered to be of limited value in the investigation of patients with partial epilepsies. Newer SPECT technologies using brain dedicated multiple detector systems have not been fully evaluated. To study the usefulness of an optimized S...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/0920-1211(95)00020-b
更新日期:1995-06-01 00:00:00
abstract:STUDY OBJECTIVE:Non-convulsive seizures/status epilepticus occur in approximately 20% of comatose, non-cardiac arrest intensive care unit (ICU) patients, and are associated with increased mortality. The prevalence and clinical significance of seizures in comatose survivors of cardiac arrest undergoing therapeutic hypot...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2013.06.018
更新日期:2013-10-01 00:00:00
abstract::Generalized epilepsy with febrile seizures plus (GEFS+) comprises a group of clinically and genetically heterogeneous epilepsy syndrome. Here, we provide the first report of clinical presentation and mutational analysis of SCN1A gene in 36 Malaysian GEFS+ patients. Mutational analysis of SCN1A gene revealed twenty sev...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2012.08.004
更新日期:2012-12-01 00:00:00
abstract::We examined the influence of seizures and carbamazepine (CBZ) on spiking rates in kindled cats. In the first experiment, spiking rates were measured before and after seizures, with and without CBZ. CBZ was administered immediately after seizures in order not to affect them. Spiking rates were measured over 9 h during ...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/0920-1211(91)90065-n
更新日期:1991-04-01 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::Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels have been implicated in the pathogenesis of epilepsy and consequently as targets for anticonvulsant drugs. Consistent with this, broad-spectrum block of HCN-mediated current (Ih) reduces seizure susceptibility in a variety of epilepsy models. However, ...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2020.106484
更新日期:2020-12-01 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:BACKGROUND:High frequency oscillations (HFOs) have provided a new insight in understanding ictogenesis and seizure localization. In absence seizures, HFOs were predominantly localized in the medial prefrontal cortex (MPFC) in MEG studies. METHODS:We studied HFOs (80-250 Hz) in scalp EEGs in patients with absence epile...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2015.06.008
更新日期:2015-09-01 00:00:00
abstract::A battery of psychometric tests was administered to 110 patients with epilepsy and to 24 non-epileptic controls. Eighty-four patients had been established on treatment with a single anticonvulsant drug (35 carbamazepine (CBZ), 30 sodium valproate (VPA), 19 phenytoin (PHT)) at unaltered dosage for the previous 3 months...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/0920-1211(90)90018-q
更新日期:1990-12-01 00:00:00
abstract:PURPOSE:To perform a systematic review and meta-analysis to identify risk factors associated with early seizure (ES) or late seizure (LS) onset in adults following stroke. DATA SOURCES:Electronic databases (MEDLINE and EMBASE), archives of stroke or epilepsy patients, and bibliographies of relevant articles, which wer...
journal_title:Epilepsy research
pub_type: 杂志文章,meta分析,评审
doi:10.1016/j.eplepsyres.2014.09.030
更新日期:2014-12-01 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:PURPOSE:The stringent dichotomy between focal and generalized epilepsies has become a contentious issue, since neuropathological studies as well as structural and functional imaging data hypothesized the existence of focal brain abnormalities in patients with well-documented idiopathic generalized epilepsy. The aim of ...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/s0920-1211(02)00084-0
更新日期:2002-08-01 00:00:00
abstract::Polyamine (tissue) concentrations have been studied in hippocampus and temporal neocortex from patients with temporal lobe epilepsy. Depth electrode recordings demonstrated hippocampal origin of the seizures, the temporal neocortex being involved during the discharge propagation. Neuropathological examination of excis...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/0920-1211(92)90035-r
更新日期:1992-07-01 00:00:00
abstract::Novel treatments for epilepsy are necessary because many epilepsy patients are resistant to medication. Metabotropic glutamate receptors (mGluRs), specifically mGluR 2 and 3, may serve as antiepileptic drug targets because of their role in controlling synaptic release. In this study, we administered a Group 2 mGluR ag...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2013.10.009
更新日期:2014-02-01 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: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:OBJECTIVE:To clarify the clinical and neurophysiological profiles of fronto-parietal opercular epilepsy in which epileptic spikes are detected with magnetoencephalography (MEG) but not with scalp electroencephalography (EEG). METHODS:Four patients presented with epileptic spikes localized to the fronto-parietal opercu...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2012.05.003
更新日期:2012-11-01 00:00:00
abstract::A single-dose study of the beta-carboline, ZK 95962, on photosensitive generalized paroxysmal activity in the EEG was conducted in 6 patients with primary generalized epilepsy. Four of the patients were newly diagnosed and did not receive any antiepileptic drug or other medication during the study. Two were receiving ...
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(90)90032-q
更新日期:1990-03-01 00:00:00
abstract:PURPOSE:The aim of this study was to investigate by a prospective, self-controlled method, whether treatment with carbamazepine (CBZ) and sodium valproate (VPA) monotherapy may alter serum lipoprotein (a) [Lp(a)] concentrations in epileptic children. METHODS:Serum Lp(a) concentrations have been determined in 18 epilep...
journal_title:Epilepsy research
pub_type: 临床试验,杂志文章
doi:10.1016/j.eplepsyres.2006.05.002
更新日期:2006-08-01 00:00:00
abstract::Application of 4-aminopyridine (4-AP, 100μM) in a solution containing 0.6mM Mg(2+) and 1.2mM Ca(2+) to hippocampal-entorhinal-perirhinal slices of adult rat brain induced ictal-like epileptiform activity in entorhinal and perirhinal cortices as revealed by electrophysiological field potential recordings. The ictal-lik...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2011.01.017
更新日期:2011-05-01 00:00:00
abstract::The severe seizure genetically epilepsy-prone rat (GEPR-9) is characterized by a broad-based seizure predisposition and is increasingly recognized as a useful model of epilepsy. When sound stimulated, members of the GEPR-9 colony exhibit complete tonic extensor convulsions. Female GEPR-9s appear to experience a higher...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/0920-1211(88)90039-3
更新日期:1988-09-01 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::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