Abstract：
:Glutamatergic ionotropic and metabotropic receptor modulators have been shown to produce anticonvulsant activity in a number of animal seizure models, e.g. maximal electroshock (MES) and DBA/2 sensory-induced seizures. The 6 Hz model of partial seizures is an alternative low frequency, long duration stimulation paradigm resulting in a seizure characterized by jaw and forelimb clonus, immobility, and an elevated tail (Straub-tail). A unique aspect of this model is that it is the only acute electrically-induced seizure model in which levetiracetam has displayed anticonvulsant activity, suggesting that the 6 Hz seizure model may be useful in identifying compounds with unique anticonvulsant profiles. The purpose of the present study was to examine the role of glutamate receptors in the MES and 6 Hz seizure models using a number of NMDA, AMPA/KA, and mGlu receptor modulators. The pharmacological profile of the 6 Hz seizure model was compared to that of the MES model using eight ionotropic glutamate receptor antagonists and eight mGlu receptor modulators. The ionotropic receptor antagonists MK-801, LY235959, NBQX, LY293558, GYKI 52466, LY300168, and LY377770 produced complete protection from tonic extension in the MES model. Furthermore, the noncompetitive mGlu1 (LY456236) and mGlu5 (MPEP) metabotropic receptor antagonists and the mGlu8 metabotropic receptor agonist (PPG) were also effective in the MES model whereas the competitive mGlu1 (LY367385) receptor antagonist, the mGlu2/3 (LY379268 and LY389795) and Group III (L-AP4) metabotropic receptor agonists were ineffective. In contrast, all of the compounds tested, produced dose-dependent protection in the 6 Hz model with an increase in potency as compared to the MES model. The largest protective indices (P.I.=TD50/ED50) observed were associated with the iGlu5 antagonist LY382884 and the mGlu2/3 receptor agonists LY379268 and LY389795 (P.I.=>14, 14, and 4.9, respectively) in the 6 Hz model. The results from the present study support the continued search for glutamate receptor modulators as potential antiepileptic agents. Furthermore these results illustrate the importance of using several different animal seizure models in the search for novel AEDs and the potential utility of the 6 Hz seizure model in identifying novel AEDs.
journal_name
Epilepsy Resjournal_title
Epilepsy researchauthors
Barton ME,Peters SC,Shannon HEdoi
10.1016/j.eplepsyres.2003.08.001subject
Has Abstractpub_date
2003-09-01 00:00:00pages
17-26issue
1eissn
0920-1211issn
1872-6844pii
S0920121103001360journal_volume
56pub_type
杂志文章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：:The genes of two group III metabotropic glutamate receptors, mGluR7 and 8, are candidate susceptibility genes for epilepsy. The Tyr433Phe polymorphism of mGluR7 and a novel polymorphism in the mGluR8 gene located 29 bp after the termination codon (2756C/T) were investigated in case control association studies performe...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/s0920-1211(99)00096-0
更新日期：2000-03-01 00:00:00
abstract：:A partially purified extract from American ginseng has been shown to have anticonvulsant activity. To identify the active components in this extract, the activities of the individual ginsenosides (Rb(1), Rb(3) and Rd), mixtures of the purified ginsenosides and a newly prepared Rb fraction were determined. One hour aft...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/j.eplepsyres.2006.05.010
更新日期：2006-08-01 00:00:00
abstract：:Post-stroke seizures occur in 5-20% of patients. Modeling of stroke-induced seizures in animals provides a useful tool for investigating the molecular basis of epileptogenesis and for developing therapies for stroke patients at increased risk for epileptogenesis. The questions addressed in the study were: (1) Do rats ...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/s0920-1211(03)00034-2
更新日期：2003-04-01 00:00:00
abstract：:Comorbid conditions may affect the quality of life in persons with epilepsy (PWE) more than seizures. Using legally mandated healthcare encounter data, somatic, psychiatric, and neurodevelopmental comorbidities in a large population-based cohort of PWE, were compared to persons with migraine (PWM), a similar neurologi...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/j.eplepsyres.2013.12.002
更新日期：2014-02-01 00:00:00
abstract：UNLABELLED:Gabapentin (GBP) is a non-metabolized antiepileptic drug that is eliminated by renal excretion and displays saturable, dose dependent absorption. The recommended dosing schedule for GBP is t.i.d. At large daily doses, oral bioavailability (F) may be improved by giving the daily dose more frequently. OBJECTI...
journal_title：Epilepsy research
pub_type： 临床试验,杂志文章
doi：10.1016/s0920-1211(98)00020-5
更新日期：1998-07-01 00:00:00
abstract：:Treating a patient with antiepileptic drugs (AEDs) may give rise to unexpected life-threatening adverse events. Despite extensive experimental and clinical testing to ensure safety, most AEDs on the market have been associated with cases of severe cutaneous reactions, serious hematological disorders, or hepatic failur...
journal_title：Epilepsy research
pub_type： 杂志文章,评审
doi：10.1016/s0920-1211(01)00306-0
更新日期：2001-11-01 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：OBJECTIVE:Aphasic status epilepticus (ASE), although rare, may often remain underdiagnosed. We aimed to report the patients diagnosed with ASE and describe their clinical presentation, etiology, electrophysiological findings, neuroimaging, treatment options, and outcome. METHODS:We retrospectively analyzed a series of...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/j.eplepsyres.2020.106479
更新日期：2020-11-01 00:00:00
abstract：PURPOSE:The present study was planned as there is paucity of outcome data of children with infantile spasms, from India where profile of patients is different from the western world. Moreover, most previous studies have either not used strict inclusion criteria or standardized psychometric tests for developmental outco...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/j.eplepsyres.2013.12.009
更新日期：2014-03-01 00:00:00
abstract：:Weak relationships have been reported between subjective complaints of memory deficits and memory performance in neuropsychological tests in patients with temporal lobe epilepsy (TLE). This study investigated whether the individual exposure to cognitive demands in daily life contributes to cancel out the performance-c...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/s0920-1211(98)00072-2
更新日期：1998-11-01 00:00:00
abstract：:The Third Eilat Conference on New Antiepileptic Drugs was held at the Royal Beach Hotel from May 27 to May 30, 1996. Epileptologists and scientists from 20 countries attended the conference, which was held to discuss critical issues in drug development, new antiepileptic drugs (AEDs) in development, progress reports a...
journal_title：Epilepsy research
pub_type：
doi：10.1016/s0920-1211(96)00081-2
更新日期：1996-11-01 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：:Two hundred and thirty-five patients suffering from newly diagnosed epilepsy were randomly allocated to treatment with either oxcarbazepine or carbamazepine in a double-blind multi-centre study. After a titration phase (between 4 and 8 weeks), the optimal individual dose of trial medication was determined and treatmen...
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(89)90070-3
更新日期：1989-01-01 00:00:00
abstract：:This study aimed to assess neuropsychiatric comorbidities and analyze risk factors in Chinese children with epilepsy. Children with epilepsy aged between 6 and 16 years from the Children's Hospital of Fudan University were included. Children with asthma and typically developing children were matched for age and gender...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/j.eplepsyres.2017.11.011
更新日期：2018-02-01 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：:Use of non-vitamin K antagonist oral anticoagulants (NOACs), including dabigatran etexilate, rivaroxaban, apixaban, edoxaban or betrixaban provides a safe and convenient alternative to the traditional anticoagulation with vitamin K antagonists or heparin derivatives. Many patients receiving long-term seizure prophylax...
journal_title：Epilepsy research
pub_type： 杂志文章,评审
doi：10.1016/j.eplepsyres.2020.106304
更新日期：2020-05-01 00:00:00
abstract：:Mutations in genes encoding ion channels in brain neurons have been identified in various epilepsy syndromes. In neuronal networks, "gain-of-function" of channels in excitatory neurotransmission could lead to hyper-excitation while "loss-of-function" in inhibitory transmission impairs neuronal inhibitory system, both ...
journal_title：Epilepsy research
pub_type： 杂志文章,评审
doi：10.1016/j.eplepsyres.2005.12.007
更新日期：2006-08-01 00:00:00
abstract：:A strain of Wistar rats, genetic absence epilepsy rats from Strasbourg (GAERS), was selected and inbred over 40 generations for occurrence of spontaneous spike-wave discharges characteristic of absence seizures, simultaneously with a strain of non-epileptic rats (NER). GAERS demonstrate an excessive sensitivity to ant...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/s0920-1211(01)00292-3
更新日期：2001-11-01 00:00:00
abstract：:Quantifying epileptiform discharges before and after the initiation of treatment can be useful for evaluating the efficacy of antiepileptic drugs in generalized epilepsy. The aim of this study was to determine if the selective α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor antagonist perampanel ...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/j.eplepsyres.2020.106378
更新日期：2020-09-01 00:00:00
abstract：:We planned this study to investigate the frequency of epilepsy in paralytic polio survivors. We analyzed the clinical data of 91 paralytic polio survivors. Patients who had been diagnosed with epilepsy were examined by electroencephalography and brain magnetic resonance imaging. 11 of the 91 patients had epilepsy (12%...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/j.eplepsyres.2011.08.019
更新日期：2012-01-01 00:00:00
abstract：OBJECTIVE:To assess the correlation between time of day and sleep-wake state prior to seizure onset for seizures recorded in an inpatient epilepsy monitoring unit. METHODS:We prospectively enrolled a consecutive series of patients undergoing inpatient epilepsy monitoring. For each epileptic seizure recorded, continuou...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/j.eplepsyres.2020.106524
更新日期：2021-01-01 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:Diffusion tensor imaging (DTI) provides information about magnitude (diffusivity) and directionality (anisotropy, FA) of water diffusion. We explored the characteristics of pathology-proven cortical dysplasia (CD) in the posterior quadrant in a case series of three patients using DTI measures, to assess associa...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/j.eplepsyres.2010.03.006
更新日期：2010-08-01 00:00:00
abstract：:Photosensitive epilepsy (PSE) offers a highly reproducible model to investigate whether changes in neuronal activity preceding the transition to an epileptic photoparoxysmal response (PPR) may be detected. We investigated this possibility in patients with idiopathic PSE using MEG, as well as normal controls and non-ph...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/j.eplepsyres.2011.10.022
更新日期：2011-12-01 00:00:00
abstract：BACKGROUND:Many new antiepileptic drugs (AEDs) have become available in recent years. Investigations of prescription patterns and exposure of AEDs to different patient groups are important regarding drug safety aspects. The aim of this study was to investigate the use of AEDs in epilepsy, with focus on exposure of AEDs...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/j.eplepsyres.2011.02.012
更新日期：2011-06-01 00:00:00
abstract：:This study was planned so as to evaluate whether magnetic field exposure has any significant effect on the pentylenetetrazol (PTZ)-induced seizures. Mice were exposed to 50 Hz, 2 G (0.2 mT) magnetic field in glass cages for 1 h. Sham exposure was produced by turning off the current while the animals were in the same e...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/s0920-1211(00)00193-5
更新日期：2001-04-01 00:00:00
abstract：:In rats with electrodes implanted in the hippocampus or amygdala, the effect was studied of a single episode of low frequency stimulation (125 msec, biphasic 4 Hz, for 1 min at a current 50% of threshold for after-discharge), LFS, on the after-discharge thresholds (ADTs) during the course of hippocampal and amygdaloid...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/0920-1211(89)90029-6
更新日期：1989-05-01 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：AIMS:To investigate the pathophysiology of pharmacoresistant epilepsies with cryptogenic generalised tonic-clonic seizures (GTCS) from infancy. METHODS:18F-Deoxy-Glucose-Positron Emission Tomography 18FDG-PET) with statistical parametric mapping (SPM). Inclusion criteria were: pharmacoresistant chronic epilepsy with G...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/j.eplepsyres.2004.05.006
更新日期：2004-06-01 00:00:00
