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Antiepileptics

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https://www.readbyqxmd.com/read/28934547/multifunctional-hybrid-compounds-derived-from-2-2-5-dioxopyrrolidin-1-yl-3-methoxypropanamides-with-anticonvulsant-and-antinociceptive-properties
#1
Michał Abram, Mirosław Zagaja, Szczepan Mogilski, Marta Andres-Mach, Gniewomir Latacz, Sebastian Baś, Jarogniew J Łuszczki, Katarzyna Kieć-Kononowicz, Krzysztof Kamiński
The focused set of new pyrrolidine-2,5-diones as potential broad-spectrum hybrid anticonvulsants was described. These derivatives integrate on the common structural scaffold the chemical fragments of well-known antiepileptic drugs such as ethosuximide, levetiracetam, and lacosamide. Such hybrids demonstrated effectiveness in two of the most widely used animal seizure models, namely, the maximal electroshock (MES) test and the psychomotor 6 Hz (32 mA) seizure model. Compound 33 showed the highest anticonvulsant activity in these models (ED50 MES = 79...
September 21, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28932875/-severe-cutaneous-drug-reactions-in-children
#2
REVIEW
M Mockenhaupt
Among severe drug reactions in children, besides Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), a specific form of hypersensitivity syndrome which is nowadays known as "drug reaction with eosinophilia and systemic symptoms" (DRESS) has to be mentioned. Whereas SJS/TEN is considered one reaction entity of different severity, DRESS has to be distinguished from SJS/TEN but also from other severe exanthems due to multiorgan involvement. Although SJS/TEN is generally referred to as a drug reaction, only about 75% of all cases are actually caused by medications and in children it is only about 50%...
September 20, 2017: Der Hautarzt; Zeitschrift Für Dermatologie, Venerologie, und Verwandte Gebiete
https://www.readbyqxmd.com/read/28931473/psychiatric-and-behavioral-side-effects-of-antiepileptic-drugs-in-adults-with-epilepsy
#3
Baibing Chen, Hyunmi Choi, Lawrence J Hirsch, Austen Katz, Alexander Legge, Richard Buchsbaum, Kamil Detyniecki
PURPOSE: Psychiatric and behavioral side effects (PBSEs) are common, undesirable effects associated with antiepileptic drug (AED) use. The objective of the study was to compare the PBSE profiles of older and newer AEDs in a large specialty practice-based sample of patients diagnosed with epilepsy. METHODS: As part of the Columbia and Yale AED Database Project, we reviewed patient records including demographics, medical history, AED use, and side effects for 4085 adult patients (age: 18 years) newly started on an AED regimen...
September 17, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28931341/the-neurotoxic-effects-of-prenatal-gabapentin-and-oxcarbazepine-exposure-on-newborn-rats
#4
Zuleyha Erisgin, Bulent Ayas, Jens R Nyengaard, N Ercument Beyhun, Yuksel Terzi
Teratogenicity is a problematic issue for pregnant women because of x-ray radiation, drugs, genetic and unknown variables. First generation antiepileptic drugs (AED) like valproic acid are well-known teratogens for developing foetuses. However, their usage is necessary in order to prevent maternal seizures. The underlying mechanism of birth defects associated with AED exposure remains unclear and information about the neurotoxic effects of prenatal exposure to AED is still limited. Oxcarbazepine (OXC) and gabapentin (GBP) are second generation antiepileptic drugs...
September 20, 2017: Journal of Maternal-fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/28929357/risk-based-bioequivalence-recommendations-for-antiepileptic-drugs
#5
REVIEW
Zhichuan Li, Lanyan Fang, Wenlei Jiang, Myong-Jin Kim, Liang Zhao
PURPOSE OF REVIEW: This review summarizes the current FDA practice in developing risk- and evidence-based product-specific bioequivalence guidances for antiepileptic drugs (AEDs). RECENT FINDINGS: FDA's product-specific guidance (PSG) for AEDs takes into account the therapeutic index of each AED product. Several PSGs for AEDs recommend fully replicated studies and a reference-scaled average bioequivalence (RS-ABE) approach that permit the simultaneous equivalence comparison of the mean and within-subject variability of the test and reference products...
September 19, 2017: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/28927716/the-effects-of-lifestyle-modification-and-statin-therapy-on-the-circulatory-markers-for-vascular-risk-in-patients-with-epilepsy
#6
Dong Wook Kim, Hyun Kyung Kim, Eun-Kee Bae
Although long-term therapy with antiepileptic drugs can increase the risk of vascular diseases, there have been little attempts to reduce the increased vascular risk in patients with epilepsy. We conducted a prospective longitudinal study to assess the effects of lifestyle modification and 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor (statin) therapy on the increased circulatory markers for vascular risk in patients with epilepsy. We recruited patients with increased vascular risk such as a history of vascular events or hypercholesterolemia, and they decided whether to be treated with statin or just to modify their lifestyle...
September 15, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28927713/risk-factors-of-early-adverse-drug-reactions-with-phenytoin-a-prospective-inpatient-cohort
#7
Reinaldo Uribe-San-Martín, Ethel Ciampi, Wilhelm Uslar, Silvana Villagra, Jaime Godoy, Patricio Mellado
INTRODUCTION: Phenytoin (PHT) is an effective and inexpensive antiepileptic drug (AED). However, its use has been limited for fear of adverse drug reactions (ADRs) and is being replaced by newer AED, increasing the costs and causing major budget problems, particularly for developing countries. OBJECTIVE: The objective of this study was to determine ADR frequency, explore, and establish related risk factors. METHODS: Prospective data were collected from a cohort of inpatients using PHT for the first time...
September 15, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28927712/real-world-data-on-rufinamide-treatment-in-patients-with-lennox-gastaut-syndrome-results-from-a-european-noninterventional-registry-study
#8
Marina Nikanorova, Christian Brandt, Stéphane Auvin, Rob McMurray
INTRODUCTION: Rufinamide is approved for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients aged ≥4years. The objective of this study was to provide real-world, long-term data on patients with LGS initiating rufinamide as add-on therapy and patients with LGS receiving other antiepileptic drugs (AEDs). METHODS: A Phase IV, noninterventional, multicenter registry study was conducted in patients with LGS aged ≥4years requiring modification to any AED treatment, including initiation of add-on rufinamide therapy...
September 15, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28927402/effects-of-premedication-with-oral-gabapentin-on-intraocular-pressure-changes-following-tracheal-intubation-in-clinically-normal-dogs
#9
Alexandra Trbolova, Masoud Selk Ghaffari, Igor Capik
BACKGROUND: Gabapentin is an antiepileptic drug widely approved as an add-on therapy for epilepsy treatment in human and dogs. There is a clinical impression that gabapentin is a suitable drug which attenuates the IOP elevation associated with tracheal intubation in humans. The present study performed to determine the effects of oral gabapentin on intraocular pressure (IOP) changes following tracheal intubation in dogs. RESULTS: Twenty adult healthy dogs were randomly assigned to treatment (n = 10) and control (n = 10) groups...
September 19, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/28926841/beneficial-combination-of-lacosamide-with-retigabine-in-experimental-animals-an-isobolographic-analysis
#10
Jarogniew J Luszczki, Mirosław Zagaja, Barbara Miziak, Maria W Kondrat-Wrobel, Katarzyna Zaluska, Paula Wroblewska-Luczka, Piotr Adamczuk, Stanislaw J Czuczwar, Magdalena Florek-Luszczki
BACKGROUND/AIM: To isobolographically determine the types of interactions that occur between retigabine and lacosamide (LCM; two third-generation antiepileptic drugs) with respect to their anticonvulsant activity and acute adverse effects (sedation) in the maximal electroshock-induced seizures (MES) and chimney test (motor performance) in adult male Swiss mice. METHODS: Type I isobolographic analysis for nonparallel dose-response effects for the combination of retigabine with LCM (at the fixed-ratio of 1:1) in both the MES and chimney test in mice was performed...
September 20, 2017: Pharmacology
https://www.readbyqxmd.com/read/28926353/randomized-double-blind-placebo-and-active-comparator-controlled-crossover-study-evaluating-the-abuse-potential-of-the-antiepileptic-drug-lacosamide-in-healthy-recreational-drug-users
#11
Kerri A Schoedel, Jens-Otto Andreas, Pamela Doty, Klaus Eckhardt, Edward M Sellers
PURPOSE: This phase 1, randomized, double-blind, placebo- and active comparator-controlled crossover study assessed the abuse potential of the antiepileptic drug, lacosamide. METHODS: After a qualification phase, 38 healthy, recreational central nervous system-depressant users were randomized to treatment sequences comprising single oral therapeutic (200 mg) and supratherapeutic (800 mg) doses of lacosamide, alprazolam (1.5 and 3 mg), and placebo. Subjective effects were assessed for 24 hours following each dose using a range of scales, with a 5- to 9-day washout between treatments...
September 18, 2017: Journal of Clinical Psychopharmacology
https://www.readbyqxmd.com/read/28923014/scn8a-mutations-in-chinese-patients-with-early-onset-epileptic-encephalopathy-and-benign-infantile-seizures
#12
Jiaping Wang, Hua Gao, Xinhua Bao, Qingping Zhang, Jiarui Li, Liping Wei, Xiru Wu, Yan Chen, Shujie Yu
BACKGROUND: SCN8A mutations have recently been associated with epilepsy and neurodevelopmental disorders. This study aimed to broaden the phenotypic-spectrum of disease related with SCN8A mutations. METHODS: To identify the pathogenic gene of a Chinese family, in which six members suffered from epilepsy, whole-exome sequencing was performed. In addition, target next-generation sequencing (NGS) was performed on 178 sporadic patients, who had epilepsy of unknown etiology within 6 months after birth...
September 18, 2017: BMC Medical Genetics
https://www.readbyqxmd.com/read/28921418/coping-with-phantom-limb-pain
#13
Damien P Kuffler
Phantom limb pain is a chronic neuropathic pain that develops in 45-85% of patients who undergo major amputations of the upper and lower extremities and appears predominantly during two time frames following an amputation: the first month and later about 1 year. Although in most patients the frequency and intensity of pain diminish over time, severe pain persists in about 5-10%. It has been proposed that factors in both the peripheral and central nervous systems play major roles in triggering the development and maintenance of pain associated with extremity amputations...
September 18, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28921040/euro-esli-a-european-audit-of-real-world-use-of-eslicarbazepine-acetate-as-a-treatment-for-partial-onset-seizures
#14
Vicente Villanueva, Martin Holtkamp, Norman Delanty, Juan Rodriguez-Uranga, Rob McMurray, Patricia Santagueda
The Euro-Esli study was an exploratory pooled analysis of data from 14 European clinical practice studies, which was conducted to audit the real-world effectiveness, safety, and tolerability of eslicarbazepine acetate (ESL) as an adjunctive treatment for partial-onset seizures. Retention and effectiveness were assessed after 3, 6, and 12 months of ESL treatment, and at the final visit. Safety and tolerability were assessed throughout ESL treatment by evaluating adverse events (AEs) and ESL discontinuation due to AEs...
September 18, 2017: Journal of Neurology
https://www.readbyqxmd.com/read/28919764/levetiracetam-is-associated-with-decrease-in-subclinical-epileptiform-discharges-and-improved-cognitive-functions-in-pediatric-patients-with-autism-spectrum-disorder
#15
Minjian Wang, Li Jiang, Xiaoju Tang
OBJECTIVE: Subclinical epileptiform discharges (SEDs) are common in pediatric patients with autism spectrum disorder (ASD), but the effect of antiepileptic drugs on SEDs in ASD remains inconclusive. This physician-blinded, prospective, randomized controlled trial investigated an association between the anticonvulsant drug levetiracetam and SEDs in children with ASD. METHODS: A total of 70 children with ASD (4-6 years) and SEDs identified by electroencephalogram were randomly divided into two equal groups to receive either levetiracetam and educational training (treatment group) or educational training only (control)...
2017: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/28919758/a-case-of-schizophrenia-comorbid-for-tetralogy-of-fallot-treated-with-clozapine-further-considerations-on-a-role-for-22q-11-2-in-the-proneness-for-seizures
#16
Hiroko Kashiwagi, Satoru Ikezawa, Tomiki Sumiyoshi, Atsuko Kadono, Kazuhiko Segawa, Kazuyoshi Takeda, Mayu Omori, Hisako Taguchi, Naotsugu Hirabayashi
We present a case of schizophrenia comorbid for tetralogy of Fallot, without chromosome 22q.11.2 deletion or duplication, treated successfully with a combination of clozapine and antiepileptic drugs. Although clozapine by itself initially triggered convulsive seizures, we continued it with co-administration of valproate and topiramate. This combined treatment did not affect cardiac function of the patient, who experienced a favorable clinical course in terms of symptomatology and functional outcomes. To our knowledge, we provide the first report on a patient with tetralogy of Fallot, in whom 22q...
2017: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/28919224/clinical-factors-associated-with-the-yield-of-routine-outpatient-scalp-electroencephalograms-a-retrospective-analysis-from-a-tertiary-hospital
#17
Mastura Monif, Udaya Seneviratne
The routine outpatient electroencephalogram (EEG) is most often used in the diagnosis and classification of epilepsy. The diagnostic yield of outpatient EEGs is low and the clinical factors contributing to the EEG outcome have not been well established. In this study, we sought to determine the yield and the factors predicting the EEG outcome. We retrospectively analyzed 1092 routine adult EEGs that were performed in a tertiary referral center over a period of 1year. Patient demographics, sources of referral, and indications for EEG were recorded...
September 14, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/28918631/sequential-ruthenium-catalysis-for-olefin-isomerization-and-oxidation-application-to-the-synthesis-of-unusual-amino-acids
#18
Marc Liniger, Yiyang Liu, Brian M Stoltz
How can you use a ruthenium isomerization catalyst twice? A ruthenium-catalyzed sequence for the formal two-carbon scission of allyl groups to carboxylic acids has been developed. The reaction includes an initial isomerization step using commercially available ruthenium catalysts followed by in situ transformation of the complex to a metal-oxo species, which is capable of catalyzing subsequent oxidation reactions. The method enables enantioselective syntheses of challenging α- tri- and tetrasubstituted α-amino acids including an expedient total synthesis of the antiepileptic drug levetiracetam...
September 16, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28917501/personalized-translational-epilepsy-research-novel-approaches-and-future-perspectives-part-i-clinical-and-network-analysis-approaches
#19
REVIEW
Felix Rosenow, Natascha van Alphen, Albert Becker, Andreas Chiocchetti, Ralf Deichmann, Thomas Deller, Thomas Freiman, Christine M Freitag, Johannes Gehrig, Anke M Hermsen, Peter Jedlicka, Christian Kell, Karl Martin Klein, Susanne Knake, Dimitri M Kullmann, Stefan Liebner, Braxton A Norwood, Diana Omigie, Karlheinz Plate, Andreas Reif, Philipp S Reif, Yvonne Reiss, Jochen Roeper, Michael W Ronellenfitsch, Stephanie Schorge, Gerhard Schratt, Stephan W Schwarzacher, Joachim P Steinbach, Adam Strzelczyk, Jochen Triesch, Marlies Wagner, Matthew C Walker, Frederic von Wegner, Sebastian Bauer
Despite the availability of more than 15 new "antiepileptic drugs", the proportion of patients with pharmacoresistant epilepsy has remained constant at about 20-30%. Furthermore, no disease-modifying treatments shown to prevent the development of epilepsy following an initial precipitating brain injury or to reverse established epilepsy have been identified to date. This is likely in part due to the polyetiologic nature of epilepsy, which in turn requires personalized medicine approaches. Recent advances in imaging, pathology, genetics and epigenetics have led to new pathophysiological concepts and the identification of monogenic causes of epilepsy...
September 13, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28917498/personalized-translational-epilepsy-research-novel-approaches-and-future-perspectives-part-ii-experimental-and-translational-approaches
#20
REVIEW
Sebastian Bauer, Natascha van Alphen, Albert Becker, Andreas Chiocchetti, Ralf Deichmann, Thomas Deller, Thomas Freiman, Christine M Freitag, Johannes Gehrig, Anke M Hermsen, Peter Jedlicka, Christian Kell, Karl Martin Klein, Susanne Knake, Dimitri M Kullmann, Stefan Liebner, Braxton A Norwood, Diana Omigie, Karlheinz Plate, Andreas Reif, Philipp S Reif, Yvonne Reiss, Jochen Roeper, Michael W Ronellenfitsch, Stephanie Schorge, Gerhard Schratt, Stephan W Schwarzacher, Joachim P Steinbach, Adam Strzelczyk, Jochen Triesch, Marlies Wagner, Matthew C Walker, Frederic von Wegner, Felix Rosenow
Despite the availability of more than 15 new "antiepileptic drugs", the proportion of patients with pharmacoresistant epilepsy has remained constant at about 20-30%. Furthermore, no disease-modifying treatments shown to prevent the development of epilepsy following an initial precipitating brain injury or to reverse established epilepsy have been identified to date. This is likely in part due to the polyetiologic nature of epilepsy, which in turn requires personalized medicine approaches. Recent advances in imaging, pathology, genetics, and epigenetics have led to new pathophysiological concepts and the identification of monogenic causes of epilepsy...
September 13, 2017: Epilepsy & Behavior: E&B
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