Voltage-dependent block of N-methyl-D-aspartate receptors by the novel anticonvulsant dibenzylamine, a bioactive constituent of L-(+)-beta-hydroxybutyrate.


PURPOSE:Previously we demonstrated that L-(+)-beta-hydroxybutyrate (L-BHB), acetoacetate (ACA), acetone, and dibenzylamine (DBA) were anticonvulsant in an audiogenic seizure-susceptible model, and that DBA was a bioactive contaminant identified in commercial lots of L-BHB. In the present study, we asked whether these effects could be mediated by ionotropic glutamate or gamma-aminobutyric acidA (GABAA) receptors. METHODS:We studied the effects of both stereoisomers of BHB (as well as the racemate), ACA, and DBA on N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5methyl-4-isoxazole-proprionic acid (AMPA), and GABAA receptors in cultured rodent neocortical neurons by using whole-cell voltage-clamp recording techniques. RESULTS:Only L-BHB and DBA exerted a concentration- and voltage-dependent block of NMDA-evoked currents, whereas none of the tested substrates affected AMPA- or GABA-activated currents. The kinetics of whole-cell block by L-BHB and DBA were similar, providing additional evidence that DBA is responsible for the anticonvulsant activity of L-BHB. CONCLUSIONS:BHB and ACA do not exert direct actions on GABAA or ionotropic glutamate receptors in cultured neocortical neurons. In addition, we provide additional evidence that DBA is responsible for the anticonvulsant activity of L-BHB, and that this action may be mediated in part by voltage-dependent blockade of NMDA receptors.






Donevan SD,White HS,Anderson GD,Rho JM




Has Abstract


2003-10-01 00:00:00














  • Human focal seizures are characterized by populations of fixed duration and interval.

    abstract:OBJECTIVE:We report on a quantitative analysis of data from a study that acquired continuous long-term ambulatory human electroencephalography (EEG) data over extended periods. The objectives were to examine the seizure duration and interseizure interval (ISI), their relationship to each other, and the effect of these ...


    pub_type: 杂志文章


    authors: Cook MJ,Karoly PJ,Freestone DR,Himes D,Leyde K,Berkovic S,O'Brien T,Grayden DB,Boston R

    更新日期:2016-03-01 00:00:00

  • Postmarketing experience with topiramate and cognition.

    abstract::Ideal antiepileptic drugs (AEDs) are designed to stop seizures with limited central nervous system (CNS) side effects. However, CNS-related treatment-emergent adverse events (TEAEs) often occur in patients receiving AEDs. Topiramate (TPM) is an AED proven to be safe and effective as adjunctive treatment for epilepsy p...


    pub_type: 杂志文章


    authors: Tatum WO 4th,French JA,Faught E,Morris GL 3rd,Liporace J,Kanner A,Goff SL,Winters L,Fix A,PADS Investigators. Post-marketing antiepileptic drug survey.

    更新日期:2001-09-01 00:00:00

  • Amygdala kindling of forebrain seizures and the occurrence of brainstem seizures in genetically epilepsy-prone rats.

    abstract::Forebrain seizures were kindled in rats by daily electrical stimulation of the amygdala. Genetically epilepsy-prone rats scoring 9 (GEPR-9s) on the seizure severity scale during audiogenic seizure (AGS) screening ("brainstem seizure-experienced") required fewer stimulations to achieve fully kindled seizures (forelimb ...


    pub_type: 杂志文章


    authors: Coffey LL,Reith ME,Chen NH,Mishra PK,Jobe PC

    更新日期:1996-02-01 00:00:00

  • Effect of continuous positive airway pressure treatment on seizure control in patients with obstructive sleep apnea and epilepsy.

    abstract::In patients with epilepsy, improvement in seizure control with treatment of coexisting obstructive sleep apnea (OSA) has been reported, but there is lack of data on the effect of continuous positive airway pressure (CPAP) compliance on seizure control in these patients. We examined the variability in seizure frequency...


    pub_type: 杂志文章


    authors: Vendrame M,Auerbach S,Loddenkemper T,Kothare S,Montouris G

    更新日期:2011-11-01 00:00:00

  • Prevalence and clinical features of epilepsy in a biracial United States population.

    abstract::A need for prevalence information emphasizing racial differences prompted a door-to-door survey of all residents of Copiah County, Mississippi. The fieldwork involved a complete census and an extensive screening questionnaire inquiring about diagnoses, signs, and symptoms of neurologic disease. Residents who lived in ...


    pub_type: 杂志文章


    authors: Haerer AF,Anderson DW,Schoenberg BS

    更新日期:1986-01-01 00:00:00

  • Aggravation of generalized epilepsies.

    abstract::Generalized epilepsies are treatable with a number of antiepileptic drugs (AEDs) that are effective in different seizure types and epilepsy syndromes. The mechanisms of action of these AEDs are incompletely understood but include inhibition of low-threshold calcium currents and of voltage-gated sodium channels and fac...


    pub_type: 杂志文章,评审


    authors: Berkovic SF

    更新日期:1998-01-01 00:00:00

  • Imaging the developing epileptic brain.

    abstract::Accurate identification of cortical malformations in children with epilepsy can be crucial for successful clinical management. Although standard head-coil magnetic resonance imaging (MRI) at 1.5 tesla (T) can be used to view the macrostructure of the brain, phased array technology at both 1.5 and 3T significantly impr...


    pub_type: 杂志文章


    authors: Grant PE

    更新日期:2005-01-01 00:00:00

  • Epilepsy duration, febrile seizures, and cerebral glucose metabolism.

    abstract:PURPOSE:Studies using magnetic resonance imaging have shown that reduced hippocampal volume is associated with a history of febrile seizures, the duration of epilepsy, and the number of generalized tonic-clonic seizures. It is uncertain whether these factors have the same influence on functional as on structural measur...


    pub_type: 杂志文章


    authors: Theodore WH,Kelley K,Toczek MT,Gaillard WD

    更新日期:2004-03-01 00:00:00

  • Effects of sodium valproate on diazepam: kinetic profiles in plasma, erythrocytes, and different brain areas in the rat.

    abstract::The kinetic profiles of diazepam (DZP) were investigated in plasma, erythrocytes, and discrete brain areas in the rat, and the effects of valproic acid (VPA), given as sodium valproate, on kinetic parameters were analyzed. The experiments were performed on two groups of rats treated daily for 15 days, the first receiv...


    pub_type: 杂志文章


    authors: Hariton C,Jadot G,Valli M,Mesdjian E,Mandel P

    更新日期:1985-01-01 00:00:00

  • Hyperexcitability of CA3 pyramidal cells in mice lacking the potassium channel subunit Kv1.1.

    abstract:PURPOSE:To investigate further the membrane properties and postsynaptic potentials of the CA3 pyramidal cells in mice that display spontaneous seizures because of a targeted deletion of the Kcna1 potassium channel gene (encoding the Kv1.1 protein subunit). METHODS:Intracellular recordings were obtained from CA3 pyrami...


    pub_type: 杂志文章


    authors: Lopantsev V,Tempel BL,Schwartzkroin PA

    更新日期:2003-12-01 00:00:00

  • Extrasynaptic γ-aminobutyric acid type A receptor-mediated sex differences in the antiseizure activity of neurosteroids in status epilepticus and complex partial seizures.

    abstract:OBJECTIVE:Sex differences are evident in the antiseizure activity of neurosteroids; however, the potential mechanisms remain unclear. In this study, we sought to determine whether differences in target extrasynaptic δ-subunit γ-aminobutyric acid type A (GABA-A) receptor expression and function underlie the sex differen...


    pub_type: 杂志文章


    authors: Reddy DS,Carver CM,Clossen B,Wu X

    更新日期:2019-04-01 00:00:00

  • Kentuckians' attitudes toward children with epilepsy.

    abstract::We explored Kentuckians' attitudes toward children with epilepsy. Questions compared respondents' attitudes about children with epilepsy, asthma, hyperactivity, and AIDS. Random digit dialing led to 617 completed interviews. The key questions asked concerned (a) how a pupil with each illness would alter the classroom ...


    pub_type: 杂志文章


    authors: Baumann RJ,Wilson JF,Wiese HJ

    更新日期:1995-10-01 00:00:00

  • Mutation of CHRNA2 in a family with benign familial infantile seizures: Potential role of nicotinic acetylcholine receptor in various phenotypes of epilepsy.

    abstract::Nicotinic acetylcholine receptor genes are involved mainly in nocturnal frontal epilepsy. Despite extensive studies, to date, the α2 subunit did not show a strong association with this peculiar epileptic phenotype. We report CHRNA2 missense mutation in a family with benign familial infantile seizures (BFIS). TrueSeq C...


    pub_type: 杂志文章


    authors: Trivisano M,Terracciano A,Milano T,Cappelletti S,Pietrafusa N,Bertini ES,Vigevano F,Specchio N

    更新日期:2015-05-01 00:00:00

  • Reduced thalamocortical functional connectivity in temporal lobe epilepsy.

    abstract:OBJECTIVE:In temporal lobe epilepsy (TLE), the thalamus is well known for its role in the propagation and spread of epileptiform activity. However, the integrity of thalamocortical functional connectivity (FC) in TLE and its relation to specific seizure patterns have not yet been determined. We address these issues wit...


    pub_type: 杂志文章


    authors: He X,Doucet GE,Sperling M,Sharan A,Tracy JI

    更新日期:2015-10-01 00:00:00

  • The ketogenic diet: adolescents can do it, too.

    abstract:PURPOSE:To determine both the efficacy of and compliance with the ketogenic diet in the adolescent population. METHODS:A retrospective study of 45 patients, aged 12-19 years, consecutively enrolled in a ketogenic diet program from 1994 to 2002, was performed. Thirty-seven patients were from The Johns Hopkins Medical I...


    pub_type: 杂志文章,多中心研究


    authors: Mady MA,Kossoff EH,McGregor AL,Wheless JW,Pyzik PL,Freeman JM

    更新日期:2003-06-01 00:00:00

  • Long-term effects of status epilepticus in the immature brain are specific for age and model.

    abstract:PURPOSE:Status epilepticus (SE) is more common in children than adults and has a high mortality and morbidity rate. SE in adult rats results in long-term disturbances in learning and memory, as well as an enhanced seizure susceptibility to further seizures. In contrast, a number of studies suggest that the immature bra...


    pub_type: 杂志文章


    authors: Cilio MR,Sogawa Y,Cha BH,Liu X,Huang LT,Holmes GL

    更新日期:2003-04-01 00:00:00

  • Validation of a brief screening instrument for the ascertainment of epilepsy.

    abstract:PURPOSE:To validate a brief screening instrument for identifying people with epilepsy in epidemiologic or genetic studies. METHODS:We designed a nine-question screening instrument for epilepsy and administered it by telephone to individuals with medical record-documented epilepsy (lifetime history of >or=2 unprovoked ...


    pub_type: 杂志文章


    authors: Ottman R,Barker-Cummings C,Leibson CL,Vasoli VM,Hauser WA,Buchhalter JR

    更新日期:2010-02-01 00:00:00

  • Infantile spasms in Down syndrome: good response to a short course of vigabatrin.

    abstract:PURPOSE:To evaluate the efficacy of vigabatrin (VGB) in the treatment of infantile spasms (ISs) associated with Down syndrome (DS) and to assess the feasibility of early discontinuation to reduce the possible retinal toxicity. METHODS:Five children with ISs with DS were treated with vigabatrin as first-line monotherap...


    pub_type: 临床试验,杂志文章


    authors: Nabbout R,Melki I,Gerbaka B,Dulac O,Akatcherian C

    更新日期:2001-12-01 00:00:00

  • Epilepsy, antiepileptic drugs, and the risk of spontaneous abortion.

    abstract::The possible effect of in utero antiepileptic drug (AED) exposure on the incidence of spontaneous abortion was evaluated among pregnancies of women with epilepsy and the wives of men with epilepsy. The proportion of pregnancy outcomes terminating in spontaneous abortion, the gestational age-specific rates of spontaneo...


    pub_type: 杂志文章


    authors: Annegers JF,Baumgartner KB,Hauser WA,Kurland LT

    更新日期:1988-07-01 00:00:00

  • COVID-19 outbreak: The impact of stress on seizures in patients with epilepsy.

    abstract:OBJECTIVE:Stress is a known trigger for seizures in patients with epilepsy (PWE). However, the association between stress and seizures has not been thoroughly investigated. In December 2019, an outbreak of coronavirus disease (COVID-19) occurred in Wuhan, Hubei province, China, causing tremendous collateral stress. Thi...


    pub_type: 杂志文章


    authors: Huang S,Wu C,Jia Y,Li G,Zhu Z,Lu K,Yang Y,Wang F,Zhu S

    更新日期:2020-09-01 00:00:00

  • The burden of decisional uncertainty in the treatment of status epilepticus.

    abstract:OBJECTIVE:Treatments for convulsive status epilepticus (SE) have a wide range of effectiveness. The estimated effectiveness of non-intravenous benzodiazepines (non-IV BZDs) ranges from approximately 70% to 90% and the estimated effectiveness of non-benzodiazepine antiseizure medications (non-BZD ASMs) ranges from appro...


    pub_type: 杂志文章


    authors: Sánchez Fernández I,Gaínza-Lein M,Barcia Aguilar C,Amengual-Gual M,Loddenkemper T

    更新日期:2020-10-01 00:00:00

  • Effect of anticonvulsants on cortical focal seizure in cats.

    abstract::Electrical stimulation of the visual cortex evoked the cortical focal seizure restricted in the neighbor cortex of the stimulated area in gallamine-immobilized cats. The present experiment was performed to clarify the participation of anticonvulsants in the cortex itself. Phenytoin and carbamazepine depressed the foca...


    pub_type: 杂志文章


    authors: Ito T,Hori M,Yoshida K,Shimizu M

    更新日期:1977-03-01 00:00:00

  • Technical aspects of pediatric epilepsy surgery: Report of a multicenter, multinational web-based survey by the ILAE Task Force on Pediatric Epilepsy Surgery.

    abstract::Surgical techniques may vary extensively between centers. We report on a web-based survey aimed at evaluating the current technical approaches in different centers around the world performing epilepsy surgery in children. The intention of the survey was to establish technical standards. A request was made to 88 center...


    pub_type: 杂志文章,多中心研究


    authors: Cukiert A,Rydenhag B,Harkness W,Cross JH,Gaillard WD,Task Force for Pediatric Epilepsy Surgery for the ILAE Commissions of Pediatrics and Surgical Therapies.

    更新日期:2016-02-01 00:00:00

  • Prostaglandin E(2) potentiates methylmalonate-induced seizures.

    abstract:PURPOSE:Methylmalonic acidemias are inherited metabolic disorders characterized by methylmalonate (MMA) accumulation and neurologic dysfunction, including seizures. It is known that metabolic crises in affected patients are precipitated by infections. Although growing evidence supports that inflammation facilitates sei...


    pub_type: 杂志文章


    authors: Salvadori MG,Banderó CR,Jesse AC,Gomes AT,Rambo LM,Bueno LM,Bortoluzzi VT,Oliveira MS,Mello CF

    更新日期:2012-01-01 00:00:00

  • The timelines of MRI findings related to outcomes in adult patients with new-onset refractory status epilepticus.

    abstract:OBJECTIVE:To identify the timelines of magnetic resonance imaging (MRI) abnormalities and their relationships with the clinical outcomes of patients with new-onset refractory status epilepticus (NORSE). METHODS:This retrospective observational study enrolled patients with NORSE who were admitted from March 2008 to Jul...


    pub_type: 杂志文章


    authors: Kim HJ,Lee SA,Kim HW,Kim SJ,Jeon SB,Koo YS

    更新日期:2020-08-01 00:00:00

  • Mechanisms of video-game epilepsy.

    abstract:PURPOSE:We aimed to elucidate the mechanisms underlying video-game epilepsy by comparing the flicker- and spatial-frequency ranges over which photic and pattern stimulation elicited photoparoxysmal responses in two different populations: (a) 25 patients with a history of seizures experienced while playing video games; ...


    pub_type: 杂志文章


    authors: Fylan F,Harding GF,Edson AS,Webb RM

    更新日期:1999-01-01 00:00:00

  • Recurrent seizures and behavior problems in children with first recognized seizures: a prospective study.

    abstract:PURPOSE:Children with epilepsy have high rates of behavior problems. The purpose was to describe prospectively the association of seizures and behavior problems in children with new-onset seizures. METHODS:Subjects were 224 children with new-onset seizures (aged 4-14 years) and 159 siblings (4-18 years). Caregiver's r...


    pub_type: 杂志文章


    authors: Austin JK,Dunn DW,Caffrey HM,Perkins SM,Harezlak J,Rose DF

    更新日期:2002-12-01 00:00:00

  • In vivo inhibition of incorporation of [U-14C]glucose into proteins in experimental focal epilepsy.

    abstract::The in vivo incorporation of [14C] from [U-14C]-glucose into rat brain proteins from different cortical areas was examined in three different experimental focal epilepsies: cobalt, freeze-lesions, and tityustoxin. When [U-14C]-glucose was injected intraperitoneally into awake and unrestrained animals with marked signs...


    pub_type: 杂志文章


    authors: Coutinho-Netto J,Boyar MM,Abdul-Ghani AS,Bradford HF

    更新日期:1982-08-01 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...


    pub_type: 杂志文章


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

    更新日期:1977-12-01 00:00:00

  • PACES in epilepsy: Results of a self-management randomized controlled trial.

    abstract:OBJECTIVE:Self-management challenges facing adults with epilepsy include limited understanding of the condition and treatment, associated psychosocial issues, and lack of community integration. Self-management interventions improve patients' medical, life role, and emotional management. Previous interventions, develope...


    pub_type: 杂志文章,随机对照试验


    authors: Fraser RT,Johnson EK,Lashley S,Barber J,Chaytor N,Miller JW,Ciechanowski P,Temkin N,Caylor L

    更新日期:2015-08-01 00:00:00