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https://www.readbyqxmd.com/read/28449218/development-and-pharmacologic-characterization-of-the-rat-6-hz-model-of-partial-seizures
#1
Cameron S Metcalf, Peter J West, Kyle E Thomson, Sharon F Edwards, Misty D Smith, H S White, Karen S Wilcox
OBJECTIVE: The mouse 6 Hz model of psychomotor seizures is a well-established and commonly used preclinical model for antiseizure drug (ASD) discovery. Despite its widespread use both in the identification and differentiation of novel ASDs in mice, a corresponding assay in rats has not been developed. We established a method for 6 Hz seizure induction in rats, with seizure behaviors similar to those observed in mice including head nod, jaw clonus, and forelimb clonus. METHODS: A convulsive current that elicits these seizure behaviors in 97% of rats (CC97 ) was determined using a Probit analysis...
April 27, 2017: Epilepsia
https://www.readbyqxmd.com/read/28434133/stiripentol-in-the-management-of-epilepsy
#2
REVIEW
Katherine C Nickels, Elaine C Wirrell
Stiripentol is a structurally unique antiepileptic drug that has several possible mechanisms of action, including diverse effects on the gamma-aminobutyric acid (GABA)-A receptor and novel inhibition of lactate dehydrogenase. Because of its inhibition of several cytochrome P450 enzymes, it has extensive pharmacokinetic interactions, which often necessitates reduction in doses of certain co-therapies, particularly clobazam. Stiripentol also has a neuroprotective action, by reducing calcium-mediated neurotoxicity...
April 22, 2017: CNS Drugs
https://www.readbyqxmd.com/read/28418172/analgesic-effect-of-clobazam-in-chronic-low-back-pain-but-not-in-experimentally-induced-pain
#3
J Schliessbach, P H Vuilleumier, A Siegenthaler, L Bütikofer, A Limacher, P Juni, H U Zeilhofer, L Arendt-Nielsen, M Curatolo
BACKGROUND: Chronic pain is frequently associated with hypersensitivity of the nervous system, and drugs that increase central inhibition are therefore a potentially effective treatment. Benzodiazepines are potent modulators of GABAergic neurotransmission and are known to exert antihyperalgesic effects in rodents, but translation into patients are lacking. This study investigates the effect of the benzodiazepine clobazam in chronic low-back pain in humans. The aim of this study is to explore the effect of GABA modulation on chronic low-back pain and on quantitative sensory tests...
April 18, 2017: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/28346953/lennox-gastaut-syndrome-a-state-of-the-art-review
#4
Mario Mastrangelo
Lennox-Gastaut syndrome (LGS) is a severe age-dependent epileptic encephalopathy usually with onset between 1 and 8 years of age. Functional neuroimaging studies recently introduced the concept of Lennox-Gastaut as "secondary network epilepsy" resulting from dysfunctions of a complex system involving both cortical and subcortical structures (default-mode network, corticoreticular connections, and thalamus). These dysfunctions are produced by different disorders including hypoxic-ischemic encephalopathies, meningoencephalitis, cortical malformations, neurocutaneous disorders, or tumors...
March 27, 2017: Neuropediatrics
https://www.readbyqxmd.com/read/28274497/development-and-validation-of-a-quantification-method-for-cucurbitacins-e-and-i-in-rat-plasma-application-to-population-pharmacokinetic-studies
#5
Giovana Maria Lanchoti Fiori, Salvatore D'Agate, Adriana Rocha, Ana Maria Soares Pereira, Oscar Della Pasqua, Norberto Peporine Lopes
Cucurbitacin E is a potential drug candidate due to its anticancer activity, recognition of its molecular targets, and synergism with other drugs used for cancer treatment. However, the use of cucurbitacin E in clinical practice is not possible because of important knowledge gaps in its preclinical and clinical pharmacokinetic characteristics. Cucurbitacin E is hydrolyzed to cucurbitacin I in plasma and in human liver microsomes. The aim of this study was to evaluate the population pharmacokinetics of cucurbitacin E and of its metabolite cucurbitacin I in rats...
February 20, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28273540/screening-of-benzodiazepines-in-thirty-european-rivers
#6
Jerker Fick, Tomas Brodin, Martina Heynen, Jonatan Klaminder, Micael Jonsson, Katerina Grabicova, Tomas Randak, Roman Grabic, Vit Kodes, Jaroslav Slobodnik, Andrew Sweetman, Mark Earnshaw, Anna Barra Caracciolo, Teresa Lettieri, Robert Loos
Pharmaceuticals as environmental contaminants have received a lot of interest over the past decade but, for several pharmaceuticals, relatively little is known about their occurrence in European surface waters. Benzodiazepines, a class of pharmaceuticals with anxiolytic properties, have received interest due to their behavioral modifying effect on exposed biota. In this study, our results show the presence of one or more benzodiazepine(s) in 86% of the analyzed surface water samples (n = 138) from 30 rivers, representing seven larger European catchments...
February 27, 2017: Chemosphere
https://www.readbyqxmd.com/read/28225210/prophylactic-drug-management-for-febrile-seizures-in-children
#7
REVIEW
Martin Offringa, Richard Newton, Martinus A Cozijnsen, Sarah J Nevitt
BACKGROUND: Febrile seizures occurring in a child older than one month during an episode of fever affect 2% to 4% of children in Great Britain and the United States and recur in 30%. Rapid-acting antiepileptics and antipyretics given during subsequent fever episodes have been used to avoid the adverse effects of continuous antiepileptic drugs. OBJECTIVES: To evaluate primarily the effectiveness and safety of antiepileptic and antipyretic drugs used prophylactically to treat children with febrile seizures; but also to evaluate any other drug intervention where there was a sound biological rationale for its use...
February 22, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28207600/advancements-in-the-critical-care-management-of-status-epilepticus
#8
Andrew Bauerschmidt, Andrew Martin, Jan Claassen
PURPOSE OF REVIEW: Status epilepticus has a high morbidity and mortality. There are little definitive data to guide management; however, new recent data continue to improve understanding of management options of status epilepticus. This review examines recent advancements regarding the critical care management of status epilepticus. RECENT FINDINGS: Recent studies support the initial treatment of status epilepticus with early and aggressive benzodiazepine dosing...
April 2017: Current Opinion in Critical Care
https://www.readbyqxmd.com/read/28183048/potential-impurities-of-anxiolytic-drug-clobazam-identification-synthesis-and-characterization-using-hplc-lc-esi-ms-n-and-nmr
#9
Neeraj Kumar, Subba Rao Devineni, Shailendra Kumar Dubey, Pramod Kumar
During the optimization of process, eight impurities (CLB Imp-A to CLB Imp-H) were detected in few of the laboratory batches of clobazam, used as anxiolytic agent, in the range of 0.02-0.12% using gradient HPLC method with UV detection. On the basis of co-spiking analysis, six impurities (CLB Imp-A to -F) enumerated by European Pharmacopoeia, however, not reported in the earlier literature, have been harmonized and found to be two impurities are completely unknown (CLB Imp-G and -H). These two new impurities structures were presumed based on LC-ESI/MS(n) study as 8-chloro-1-methyl-5-phenyl-1,5-dihydro-3H-1,5-benzodiazepine-2,4-dione (CLB Imp-G) and 5-chloro-1-methyl-3-phenyl-1H-benzo[d]imidazol-2(3H)-one (CLB Imp-H)...
January 29, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28162658/-415-effect-of-the-benzodiazepine-clobazam-in-chronic-low-back-pain-and-experimental-pain-modalities-a-randomized-placebo-controlled-crossover-study
#10
J Schliessbach, P Vuilleumier, A Siegenthaler, L Bütikofer, A Limacher, P Juni, H Zeilhofer, L Arendt-Nielsen, M Curatolo
No abstract text is available yet for this article.
April 2016: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/28094153/development-and-validation-of-a-fast-ionic-liquid-based-dispersive-liquid-liquid-microextraction-procedure-combined-with-lc-ms-ms-analysis-for-the-quantification-of-benzodiazepines-and-benzodiazepine-like-hypnotics-in-whole-blood
#11
Marieke De Boeck, Sophie Missotten, Wim Dehaen, Jan Tytgat, Eva Cuypers
To date, thorough clean-up of complex biological samples remains an essential part of the analytical process. The solid phase extraction (SPE) technique is the well-known standard, however, its main weaknesses are the labor-intensive and time-consuming protocols. In this respect, dispersive liquid-liquid microextractions (DLLME) seem to offer less complex and more efficient extraction procedures. Furthermore, ionic liquids (ILs) - liquid salts - are emerging as new promising extraction solvents, thanks to their non-flammable nature, negligible vapor pressure and easily adaptable physiochemical properties...
May 2017: Forensic Science International
https://www.readbyqxmd.com/read/28081475/add-on-stiripentol-elevates-serum-valproate-levels-in-patients-with-or-without-concomitant-topiramate-therapy
#12
Toshihiro Jogamoto, Yoshiaki Yamamoto, Mitsumasa Fukuda, Yuka Suzuki, Katsumi Imai, Yukitoshi Takahashi, Yushi Inoue, Yoko Ohtsuka
OBJECTIVE: Stiripentol (STP), valproate (VPA) and topiramate (TPM) are reported to have efficacy for Dravet syndrome. In this study, we sought to elucidate the mechanisms underlying the increased serum VPA concentrations following STP adjunctive therapy in patients with Dravet syndrome. METHODS: Twenty-eight patients with Dravet syndrome (age range, 1-35 years) undergoing combination therapy with VPA and STP were included in this study. We evaluated VPA and clobazam (CLB) serum concentrations before and after add-on STP...
February 2017: Epilepsy Research
https://www.readbyqxmd.com/read/27779771/efficacy-and-tolerability-of-antiepileptic-drugs-in-patients-with-focal-epilepsy-systematic-review-and-network-meta-analyses
#13
REVIEW
Marília Silveira de Almeida Campos, Lorena Rocha Ayres, Manuela Roque Siane Morelo, Fabiana Angelo Marques, Leonardo Régis Leira Pereira
Several newer antiepileptic drugs (AEDs) have been introduced into clinical practice, offering choices for individualizing the treatment of epilepsy since AEDs have different efficacy and tolerability profiles. In particular, questions exist regarding which AEDs are the best options for the monotherapy of focal epilepsy. Is carbamazepine (CBZ), which is considered the standard treatment for focal epilepsy, still the best option for monotherapy of focal epilepsy, despite the emergence of new AEDs? In this systematic review, we compared the relative tolerability of all available AEDs for monotherapy of all types of epilepsy as well as their efficacy in the monotherapy of focal epilepsy...
December 2016: Pharmacotherapy
https://www.readbyqxmd.com/read/27778062/cytisine-inhibits-the-protective-activity-of-various-classical-and-novel-antiepileptic-drugs-against-6%C3%A2-hz-induced-psychomotor-seizures-in-mice
#14
Piotr Tutka, Maria W Kondrat-Wróbel, Katarzyna Zaluska, Dorota Żółkowska, Magdalena Florek-Łuszczki, Jarogniew J Łuszczki
BACKGROUND: Cytisine (CYT) is a partial agonist of brain α4β2 nicotinic acetylcholine receptors widely used in Central/Eastern Europe for smoking cessation. OBJECTIVES: This study evaluated the effect of CYT on the ability of classical and novel antiepileptic drugs to prevent seizures evoked by the 6-Hz test, a model of psychomotor seizures in mice thought as a model of drug-resistant seizures. RESULTS: CYT administered intraperitoneally (i...
January 2017: Psychopharmacology
https://www.readbyqxmd.com/read/27769254/effects-of-clobazam-for-treatment-of-refractory-status-epilepticus
#15
Dominik Madžar, Anna Geyer, Ruben U Knappe, Stephanie Gollwitzer, Joji B Kuramatsu, Stefan T Gerner, Hajo M Hamer, Hagen B Huttner
BACKGROUND: Clobazam (CLB) is a well characterized antiepileptic drug (AED) that differs from other benzodiazepines by its basic chemical structure and pharmacodynamic properties. Only one previous study examined the efficacy of CLB as add-on therapy in refractory status epilepticus (RSE). METHODS: We analyzed RSE episodes treated in our institution between 2001 and 2012. Successful treatment with CLB was scored if CLB was the last AED added to therapy before RSE termination...
October 21, 2016: BMC Neurology
https://www.readbyqxmd.com/read/27768696/fine-mapping-of-a-dravet-syndrome-modifier-locus-on-mouse-chromosome-5-and-candidate-gene-analysis-by-rna-seq
#16
Nicole A Hawkins, Nicole J Zachwieja, Alison R Miller, Lyndsey L Anderson, Jennifer A Kearney
A substantial number of mutations have been identified in voltage-gated sodium channel genes that result in various forms of human epilepsy. SCN1A mutations result in a spectrum of severity ranging from mild febrile seizures to Dravet syndrome, an infant-onset epileptic encephalopathy. Dravet syndrome patients experience multiple seizures types that are often refractory to treatment, developmental delays, and elevated risk for SUDEP. The same sodium channel mutation can produce epilepsy phenotypes of varying clinical severity...
October 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27696387/cannabidiol-as-a-new-treatment-for-drug-resistant-epilepsy-in-tuberous-sclerosis-complex
#17
Evan J Hess, Kirsten A Moody, Alexandra L Geffrey, Sarah F Pollack, Lauren A Skirvin, Patricia L Bruno, Jan L Paolini, Elizabeth A Thiele
OBJECTIVE: Tuberous sclerosis complex (TSC) is an autosomal-dominant genetic disorder with highly variable expression. The most common neurologic manifestation of TSC is epilepsy, which affects approximately 85% of patients, 63% of whom develop treatment-resistant epilepsy. Herein, we evaluate the efficacy, safety, and tolerability of cannabidiol (CBD), a nonpsychoactive compound derived from the marijuana plant, as an adjunct to current antiepileptic drugs in patients with refractory seizures in the setting of TSC...
October 2016: Epilepsia
https://www.readbyqxmd.com/read/27683846/deconstructing-tolerance-with-clobazam-post-hoc-analyses-from-an-open-label-extension-study
#18
Barry E Gidal, Robert T Wechsler, Raman Sankar, Georgia D Montouris, H Steve White, James C Cloyd, Mary Clare Kane, Guangbin Peng, David M Tworek, Vivienne Shen, Jouko Isojarvi
OBJECTIVE: To evaluate potential development of tolerance to adjunctive clobazam in patients with Lennox-Gastaut syndrome. METHODS: Eligible patients enrolled in open-label extension study OV-1004, which continued until clobazam was commercially available in the United States or for a maximum of 2 years outside the United States. Enrolled patients started at 0.5 mg·kg(-1)·d(-1) clobazam, not to exceed 40 mg/d. After 48 hours, dosages could be adjusted up to 2...
October 25, 2016: Neurology
https://www.readbyqxmd.com/read/27629561/anticonvulsive-activity-in-audiogenic-dba-2-mice-of-1-4-benzodiazepines-and-1-5-benzodiazepines-with-different-activities-at-cerebellar-granule-cell-gabaa-receptors
#19
Elena Gatta, Aroldo Cupello, Mario Di Braccio, Giancarlo Grossi, Mauro Robello, Francesca Scicchitano, Emilio Russo, Giovambattista De Sarro
Herein, we tested in a model of generalized reflex epilepsy in mice different 1,4-benzodiazepines and 1,5-benzodiazepines with agonistic activity at the GABAA receptor population contributing to the peak component of the chloride current elicited by GABA in cerebellar granule cells (CGCs) in culture. The substances have all higher lipophilia than clobazam, an antiepileptic drug well known and used in human therapy. This ensures that they all can pass relatively easily the blood-brain barrier (BBB). The benzodiazepines were administered intraperitoneally (i...
December 2016: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/27596103/current-treatment-options-for-early-onset-pediatric-epileptic-encephalopathies
#20
REVIEW
Rolla Shbarou
The management of early-onset, genetically determined epilepsies is often challenging. First-line anti-epileptic drugs (AEDs) often include phenobarbital, phenytoin, oxcarbazepine, carbamazepine, clonazepam, levetiracetam, and valproic acid. Combinations of medications are used in these patients with often intractable seizures, and they include topiramate, clobazam, felbamate, lacosamide, lamotrigine, rufinamide, vigabatrin, ACTH, oral steroids, and the ketogenic diet. Vagus nerve stimulator therapy offers some relief in selected patients...
October 2016: Current Treatment Options in Neurology
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