Effects of clobazam and its active metabolite on GABA-activated currents in rat cerebral neurons in culture.

Abstract:

PURPOSE:The antiepileptic effects of clobazam, a 1,5-benzodiazepine, have been well documented in animal experiments and clinical trials. However, the drug's mechanisms of antiepileptic actions are still undetermined. The purpose of this study was to learn how clobazam and its active metabolite modulate gamma-aminobutyric acid (GABA)-activated currents in rat cerebral neurons in culture. METHODS:Whole-cell voltage-clamp recordings were performed on cultured cerebral neurons of the rat. Clobazam or its metabolite N-desmethylclobazam was dissolved in the extracellular solution and applied for 2 s by pressure ejection from a micropipette. To maintain GABA-activated currents, 2 mM Mg adenosine triphosphate (ATP) was added to the intracellular solution. RESULTS:GABA elicited outward currents that were mediated by GABAA receptor-coupled Cl- channels. Applying clobazam with 10 microM GABA elicited enhanced outward currents. Flumazenil, an antagonist of the benzodiazepine receptor, inhibited the enhancing effect of clobazam. The enhancement ratio increased as much as 2.28-fold in a dose-dependent manner at a concentration of 3 microM clobazam. However, it started to decrease at a concentration of 10 microM clobazam. The metabolite N-desmethylclobazam was tested in the same manner, and exhibited an identical dose-dependent enhancement of GABA-activated currents. CONCLUSIONS:The antiepileptic effects of the 1,5-benzodiazepines are attributed to the enhancement of GABAergic inhibitory neurotransmission. The antiepileptic effects of clobazam are thought to depend mainly on its active metabolite N-desmethylclobazam, which is present in high concentrations in patients who receive long-term clobazam. Clobazam's enhancement of GABA-activated currents was most marked on weaker GABA currents. We therefore infer that clobazam acts more efficiently on tissues in which the release of GABA is diminished.

journal_name

Epilepsia

journal_title

Epilepsia

authors

Nakamura F,Suzuki S,Nishimura S,Yagi K,Seino M

doi

10.1111/j.1528-1157.1996.tb00643.x

subject

Has Abstract

pub_date

1996-08-01 00:00:00

pages

728-35

issue

8

eissn

0013-9580

issn

1528-1167

journal_volume

37

pub_type

杂志文章
  • Effect of prolonged anticonvulsant medication in epileptic patients: serum lipids, vitamins B6, B12, and folic acid, proteins, and fine structure of liver.

    abstract::Twenty-seven epileptic patients, most from low socioeconomic groups and aged 15-54 years, were studied for effects of prolonged anticonvulsant medication. They had received the usual doses of phenobarbitone and diphenylhydantoin (PHT) regularly for 3-32 years, with control of seizures, and had not taken any B-vitamins...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/j.1528-1157.1987.tb03641.x

    authors: Dastur DK,Dave UP

    更新日期:1987-03-01 00:00:00

  • Indications and methodology for video-electroencephalographic studies in the epilepsy monitoring unit.

    abstract::Although the epilepsy and neurology communities have position papers on a number of topics pertaining to epilepsy diagnosis and management, no current paper exists for the rationale and appropriate indications for epilepsy monitoring unit (EMU) evaluation. General neurologists, hospital administrators, and insurers al...

    journal_title:Epilepsia

    pub_type: 杂志文章,评审

    doi:10.1111/epi.13938

    authors: Shih JJ,Fountain NB,Herman ST,Bagic A,Lado F,Arnold S,Zupanc ML,Riker E,Labiner DM

    更新日期:2018-01-01 00:00:00

  • Preliminary results on pregnancy outcomes in women using lamotrigine.

    abstract:PURPOSE:In 1992, the International Lamotrigine Pregnancy Registry was initiated to enroll prospectively and to monitor pregnancies exposed to lamotrigine (LTG) for the occurrence of major birth defects. This study presents results as of September 2001 on 168 outcomes exposed to LTG monotherapy and 166 outcomes after pr...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1046/j.1528-1157.2002.45901.x

    authors: Tennis P,Eldridge RR,International Lamotrigine Pregnancy Registry Scientific Advisory Committee.

    更新日期:2002-10-01 00:00:00

  • Detecting epileptic spikes.

    abstract::We present a technique for automatic detection of epileptic spikes in electroencephalogram (EEG) recordings. We used a nonlinear modeling method that enables us to detect rapidly and accurately epileptic behavior in the EEG signal. Our approach is illustrated by an application to interictal activity from a patient wit...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1046/j.1528-1157.43.s.5.7.x

    authors: Diambra L

    更新日期:2002-01-01 00:00:00

  • Fetal heart rate patterns and chronic exposure to antiepileptic drugs.

    abstract::Fetal heart rate (FHR) characteristics of fetuses exposed and not exposed to antiepileptic drugs (AEDs) were studied. FHR is considered to reflect central nervous system (CNS) integrity. Three intervals during pregnancy were investigated: 20, 32, and 38 weeks. At 32 and 38 weeks, FHR was studied in relation to quiet (...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/j.1528-1157.1992.tb02353.x

    authors: Swartjes JM,van Geijn HP,Meinardi H,Mantel R

    更新日期:1992-07-01 00:00:00

  • Febrile seizures: clinical characteristics and initial EEG.

    abstract::We examined the relationship between clinical characteristics and EEG classification in all children with febrile seizures examined at the University Pediatric Clinic, Skopje, Yugoslavia between 1982 and 1984. This is the only facility in Macedonia providing EEG or neurologic consultation for children. EEGs were class...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/j.1528-1157.1992.tb02282.x

    authors: Sofijanov N,Emoto S,Kuturec M,Dukovski M,Duma F,Ellenberg JH,Hirtz DG,Nelson KB

    更新日期:1992-01-01 00:00:00

  • The clinical usefulness of ictal SPECT in temporal lobe epilepsy: the lateralization of seizure focus and correlation with EEG.

    abstract:PURPOSE:To analyze the relationship between ictal electroencephalography (EEG) and ictal single-photon emission computed tomography (SPECT) and to evaluate the diagnostic usefulness of ictal SPECT as an independent presurgical evaluation technique. METHODS:Sixty-eight patients with temporal lobe epilepsy who underwent...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/j.1528-1157.2000.tb00278.x

    authors: Lee SK,Lee SH,Kim SK,Lee DS,Kim H

    更新日期:2000-08-01 00:00:00

  • Effects of valproate on acylcarnitines in children with epilepsy using ESI-MS/MS.

    abstract:PURPOSE:To determine the influence of valproate (VPA) treatment on acylcarnitines in children with epilepsy. METHODS:Determination of acylcarnitines (including free carnitine and acylcarnitines from C2 to C18) in dried blood spot specimens using tandem-mass spectrometry. Longitudinal study of changes in acylcarnitines...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/j.1528-1167.2006.00833.x

    authors: Werner T,Treiss I,Kohlmueller D,Mehlem P,Teich M,Longin E,Gerstner T,Koenig SA,Schulze A

    更新日期:2007-01-01 00:00:00

  • Brain amines and convulsions in four strains of parathyroidectomized, pinealectomized rat.

    abstract::The tendency for four strains of parathyroidectomized (PTx) rats to convulse after pinealectomy (Px) was observed in this experiment; telencephalic serotonin, norepinephrine, and dopamine were examined to note any correlation between amines and convulsions. The strains of rats tested were Sprague-Dawley, Wistar, Long-...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/j.1528-1157.1978.tb05023.x

    authors: Philo R,Reiter RJ

    更新日期:1978-04-01 00:00:00

  • Help-seeking patterns for children with epilepsy in rural India: implications for service delivery.

    abstract:PURPOSE:Most people in the world with epilepsy are untreated with antiepileptic drugs (AEDs). In some developing countries, this is because treatment facilities are unavailable or difficult to access. It has even been suggested that indigenous health systems threaten the prospect of the global control of epilepsy with ...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1046/j.1528-1157.2002.47601.x

    authors: Pal DK,Das T,Sengupta S,Chaudhury G

    更新日期:2002-08-01 00:00:00

  • Lack of support for a role for RLIP76 (RALBP1) in response to treatment or predisposition to epilepsy.

    abstract:BACKGROUND:Multidrug transporters are postulated to contribute to antiepileptic drug (AED) resistance. The transporter best studied is P-glycoprotein, an ATP-Binding Cassette (ABC) transporter superfamily member. RLIP76 is suggested to be an energy-dependent non-ABC transporter, reducing AED blood-brain barrier penetra...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/j.1528-1167.2007.00926.x

    authors: Soranzo N,Kelly L,Martinian L,Burley MW,Thom M,Sali A,Kroetz DL,Goldstein DB,Sisodiya SM

    更新日期:2007-04-01 00:00:00

  • Public knowledge and attitudes toward epilepsy in Kuwait.

    abstract:PURPOSE:The study was conducted to determine the familiarity with, knowledge of, misunderstandings, and attitudes toward epilepsy among the Kuwaiti population. METHODS:A pretested questionnaire was used to collect data from a sample of 784 Kuwaiti individuals, selected from five governorates in Kuwait using a multista...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/j.1528-1167.2007.01433.x

    authors: Awad A,Sarkhoo F

    更新日期:2008-04-01 00:00:00

  • Interaction of phenobarbital and phenytoin in an experimental model of seizures in rats.

    abstract::The combination of phenobarbital (PB) and phenytoin (PHT) was recommended for many years for treatment of epilepsy in humans. We tested the effectiveness of the combination in a model of hippocampal seizures termed maximal dentate activation (MDA). Two parameters of MDA were measured: duration and time to onset. Neith...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/j.1528-1157.1994.tb02936.x

    authors: Stringer JL,Higgins MG

    更新日期:1994-01-01 00:00:00

  • Use of newer antiepileptic drugs and prognosis in adults with status epilepticus: Comparison between 2009 and 2017.

    abstract::It is unclear whether the outcome of status epilepticus (SE), a neurological emergency associated with high mortality and morbidity, has changed over the past decade. We investigated the difference in prognosis (mortality, functional status at discharge) after adult SE episodes in a large registry between 2 time point...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/epi.14434

    authors: Fatuzzo D,Novy J,Rossetti AO

    更新日期:2018-07-01 00:00:00

  • Surgery for intractable infantile spasms: neuroimaging perspectives.

    abstract::Twenty-three infants and children underwent cortical resection (n = 15) or hemispherectomy (n = 8) for intractable infantile spasms. Infantile spasms were present at the time of surgery in 17 of the 23 patients; in six, spasms had evolved to other seizure types during surgical evaluation. Children with a remote histor...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/j.1528-1157.1993.tb00459.x

    authors: Chugani HT,Shewmon DA,Shields WD,Sankar R,Comair Y,Vinters HV,Peacock WJ

    更新日期:1993-07-01 00:00:00

  • Reduction of duration and severity of megimide seizures in rats on a folic acid deficient diet.

    abstract::Folic acid deficient diet reduces the duration and severity of intravenous megimide seizures in the rat after 6 months of diet. Plasma and serum folate levels are strongly reduced after that period. The difference between Lactobacillus casei and Streptococcus faecalis activity in brain show a slight, but not significa...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/j.1528-1157.1977.tb04987.x

    authors: Hommes OR,ten Berge EJ,Jansen MJ,Kok JC

    更新日期:1977-12-01 00:00:00

  • NER rat strain: a new type of genetic model in epilepsy research.

    abstract:PURPOSE:We characterized and evaluated as an animal model of epilepsy NER, a new epileptic rat strain, which was developed by inbreeding rats with spontaneous tonic-clonic seizures in a stock of Crj:Wistar. METHODS:Animals were monitored through the inbreeding course, and video-EEGs were recorded selectively. External...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/j.1528-1157.1998.tb01281.x

    authors: Noda A,Hashizume R,Maihara T,Tomizawa Y,Ito Y,Inoue M,Kobayashi K,Asano Y,Sasa M,Serikawa T

    更新日期:1998-01-01 00:00:00

  • Comparative pharmacokinetic study of chewable and conventional carbamazepine in children.

    abstract::Fifteen children (7 boys and 8 girls) with generalized tonic-clonic seizures (GTCS) and partial seizures with elementary or complex symptomatology, treated with carbamazepine (CBZ) alone (n = 7) or in combination with either phenobarbital (PB, n = 6) or clobazam (CLB, n = 2) given for at least 3 months at stable indiv...

    journal_title:Epilepsia

    pub_type: 临床试验,杂志文章

    doi:10.1111/j.1528-1157.1993.tb02390.x

    authors: Cornaggia C,Gianetti S,Battino D,Granata T,Romeo A,Viani F,Limido G

    更新日期:1993-01-01 00:00:00

  • Safety and tolerability associated with chronic intermittent use of diazepam buccal film in adult, adolescent, and pediatric patients with epilepsy.

    abstract:OBJECTIVE:Diazepam buccal film (DBF) is in development for treatment of patients experiencing bouts of increased seizure activity. We assessed safety, tolerability, and usability of self- or caregiver-administered DBF in the outpatient setting. METHODS:Patients aged 2-65 years needing treatment with a rescue benzodiaz...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/epi.16696

    authors: Seinfeld S,Gelfand MA,Heller AH,Buan C,Slatko G

    更新日期:2020-11-01 00:00:00

  • Surgical versus medical treatment for epilepsy. I. Outcome related to survival, seizures, and neurologic deficit.

    abstract::We conducted a retrospective parallel longitudinal cohort study comparing surgical and medical treatment for epilepsy. The surgical group contained 201 patients treated with resective surgery for epilepsy in Norway since the first operation in 1949 until January 1988. The 185 control group patients treated medically o...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/j.1528-1157.1991.tb04666.x

    authors: Guldvog B,Løyning Y,Hauglie-Hanssen E,Flood S,Bjørnaes H

    更新日期:1991-05-01 00:00:00

  • Ripples on rolandic spikes: A marker of epilepsy severity.

    abstract:OBJECTIVE:Children with rolandic spikes may or may not have seizures, ranging from benign rolandic epilepsy to severe atypical rolandic epilepsy. We investigated whether ripples (80-250 Hz), superimposed on rolandic spikes in surface electroencephalography (EEG), can differentiate between different entities. METHODS:I...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/epi.13423

    authors: van Klink NE,van 't Klooster MA,Leijten FS,Jacobs J,Braun KP,Zijlmans M

    更新日期:2016-07-01 00:00:00

  • Causes of status epilepticus.

    abstract::Status epilepticus (SE) is the most extreme form of epilepsy. It describes a prolonged seizure that may occur in patients with previous epilepsy or in acute disorders of the central nervous system. It is one of the most common neurologic emergencies, with an incidence of up to 41 per 100,000 per year and an estimated ...

    journal_title:Epilepsia

    pub_type: 杂志文章,评审

    doi:10.1111/j.1528-1167.2012.03622.x

    authors: Trinka E,Höfler J,Zerbs A

    更新日期:2012-09-01 00:00:00

  • Mortality after a first episode of status epilepticus in the United States and Europe.

    abstract:OBJECTIVE:In the last decade several studies have been published on incidence, etiology, and prognosis of status epilepticus (SE) with population-based data from the United States and Europe. The aim of this review is to summarize the available information on the epidemiology of SE and to outline the sources of the var...

    journal_title:Epilepsia

    pub_type: 杂志文章,评审

    doi:10.1111/j.1528-1167.2005.00409.x

    authors: Logroscino G,Hesdorffer DC,Cascino G,Hauser WA,Coeytaux A,Galobardes B,Morabia A,Jallon P

    更新日期:2005-01-01 00:00:00

  • Return to driving after a diagnosis of epilepsy: A prospective registry study.

    abstract:OBJECTIVE:To determine the frequency and predictors of return to driving within 1 year after a diagnosis of epilepsy. METHODS:SEISMIC (the Sydney Epilepsy Incidence Study to Measure Illness Consequences) was a prospective, multicenter, community-wide study of people of all ages with newly diagnosed epilepsy in Sydney,...

    journal_title:Epilepsia

    pub_type: 临床试验,杂志文章

    doi:10.1111/epi.14001

    authors: Xu Y,Hackett ML,Glozier N,Nikpour A,Somerville E,Bleasel A,Ireland C,Anderson CS

    更新日期:2018-03-01 00:00:00

  • On seeing the trees and the forest: single-signal and multisignal analysis of periictal intracranial EEG.

    abstract:PURPOSE:Epileptic seizures are associated with a dysregulation of electrical brain activity on many different spatial scales. To better understand the dynamics of epileptic seizures, that is, how the seizures initiate, propagate, and terminate, it is important to consider changes of electrical brain activity on differe...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/j.1528-1167.2012.03588.x

    authors: Schindler K,Gast H,Goodfellow M,Rummel C

    更新日期:2012-09-01 00:00:00

  • Effect of systemic estrogen on seizure susceptibility in the immature animal.

    abstract::Estrogens have previously been reported to be proconvulsants in adult animals. This study evaluated the effects of acute, high-dose estrogen administration on rate of kindling in immature rats. No significant differences in rate of kindling between the estrogen-treated rats and controls were noted. This study, using t...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/j.1528-1157.1986.tb03580.x

    authors: Schultz-Krohn WA,Thompson J,Holmes GL

    更新日期:1986-09-01 00:00:00

  • Microstructural white matter abnormality and frontal cognitive dysfunctions in juvenile myoclonic epilepsy.

    abstract:PURPOSE:Previous neuroimaging studies provide growing evidence that patients with juvenile myoclonic epilepsy (JME) have both structural and functional abnormalities of the thalamus and frontal lobe gray matter. However, limited data are available regarding the issue of white matter (WM) involvement, making the microst...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/j.1528-1167.2012.03544.x

    authors: Kim JH,Suh SI,Park SY,Seo WK,Koh I,Koh SB,Seol HY

    更新日期:2012-08-01 00:00:00

  • EEG in children with early-onset benign occipital seizure susceptibility syndrome: Panayiotopoulos syndrome.

    abstract:PURPOSE:We analyzed sequential changes in the localization of EEG foci along with age to identify a specific EEG pattern, and the relation between the clinical manifestations and the EEG pattern in patients with Panayiotopoulos syndrome (PS). METHODS:The subjects were 76 children, who had been followed up >2 years wit...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1046/j.1528-1157.2003.47702.x

    authors: Ohtsu M,Oguni H,Hayashi K,Funatsuka M,Imai K,Osawa M

    更新日期:2003-03-01 00:00:00

  • Long-term prognosis for symptomatic (secondarily) generalized epilepsies: a population-based study.

    abstract:PURPOSE:To describe the long-term outcome of childhood-onset secondarily generalized epilepsies (SGEs). METHODS:Children were identified from the Nova Scotia population-based epilepsy study (n=692). Onset of epilepsy was between 1977 and 1985, and follow-up was mainly in 2003. SGE was defined as having a mixture of mo...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/j.1528-1167.2007.01072.x

    authors: Camfield P,Camfield C

    更新日期:2007-06-01 00:00:00

  • Diagnostic utility of invasive EEG for epilepsy surgery: Indications, modalities, and techniques.

    abstract::Many patients with medically refractory epilepsy now undergo successful surgery based on noninvasive diagnostic information, but intracranial electroencephalography (IEEG) continues to be used as increasingly complex cases are considered surgical candidates. The indications for IEEG and the modalities employed vary ac...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/epi.13515

    authors: Jayakar P,Gotman J,Harvey AS,Palmini A,Tassi L,Schomer D,Dubeau F,Bartolomei F,Yu A,Kršek P,Velis D,Kahane P

    更新日期:2016-11-01 00:00:00