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Lacosamide

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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/28926841/beneficial-combination-of-lacosamide-with-retigabine-in-experimental-animals-an-isobolographic-analysis
#2
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
#3
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/28919386/comparison-of-lacosamide-versus-sodium-valproate-in-status-epilepticus-a-pilot-study
#4
Usha K Misra, Deepanshu Dubey, Jayantee Kalita
PURPOSE: The purpose of this study was to compare the efficacy and safety of lacosamide (LCM) and sodium valproate (SVA) in lorazepam (LOR)-resistant SE. METHODS: Patients with LOR-resistant SE were randomized to intravenous LCM 400mg at the rate of 60mg/kg/min or SVA 30mg/kg at the rate of 100mg/min. The SE severity score (STESS), duration of SE and its etiology, and MRI findings were noted. Primary outcome was seizure cessation for 1h, and secondary outcomes were 24h seizure remission, in-hospital death, and severe adverse events (SAE)...
September 14, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28884208/lacosamide-treatment-of-childhood-refractory-focal-epilepsy-the-first-reported-side-effect-in-paediatric-patients
#5
Edibe Pembegul Yildiz, Melis Ulak Ozkan, Gonca Bektas, Tuğçe Aksu Uzunhan, Nur Aydinli, Mine Caliskan, Meral Ozmen
PURPOSE: Lacosamide (LCM) is an effective antiepileptic drug (AED) approved for the treatment of focal epilepsy in both children and adults. The aim of this observational study was to review our centre's experience with LCM and to characterise its efficacy and tolerability as an adjunct therapy in children with refractory focal epilepsy. METHODS: We retrospectively reviewed the medical records of 12 paediatric patients who underwent treatment with LCM from January 2014 to December 2015...
September 7, 2017: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/28881259/sodium-channel-blockers-in-kcnq2-encephalopathy-lacosamide-as-a-new-treatment-option
#6
Susanne Schubert-Bast, Peter Hofstetter, Doris Fischer, Rolf Schloesser, Georgia Ramantani, Matthias Kieslich
No abstract text is available yet for this article.
September 1, 2017: Seizure: the Journal of the British Epilepsy Association
https://www.readbyqxmd.com/read/28874058/lacosamide-induced-thrombotic-thrombocytopenic-purpura
#7
Dènahin Hinnoutondji Toffa, Sepehr Mehrpouyan, Benjamin Rioux-Masse, Dang Khoa Nguyen
No abstract text is available yet for this article.
September 1, 2017: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/28866338/wake-up-to-sleep-the-effects-of-lacosamide-on-daytime-sleepiness-in-adults-with-epilepsy
#8
Nancy Foldvary-Schaefer, Silvia Neme-Mercante, Noah Andrews, Monica Bruton, Lu Wang, Shannon Morrison, James Bena, Madeleine Grigg-Damberger
OBJECTIVE: The objective of the study was to investigate the effects of lacosamide (LCM) on daytime sleepiness ascertained by the Epworth Sleepiness Scale (ESS) in adults with focal epilepsy in a randomized, controlled design. METHODS: Subjects taking ≤2 AEDs for ≥4weeks underwent polysomnography with EEG followed by the maintenance of wakefulness test (MWT) and completed the ESS and other patient-reported outcomes (PROs) at baseline, LCM 200mg/day, and LCM 400mg/day (Visit 4; V4)...
August 31, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28859122/effects-of-arachidonyl-2-chloroethylamide-acea-on-the-protective-action-of-various-antiepileptic-drugs-in-the-6-hz-corneal-stimulation-model-in-mice
#9
Jarogniew J Luszczki, Pawel Patrzylas, Miroslaw Zagaja, Marta Andres-Mach, Katarzyna Zaluska, Maria W Kondrat-Wrobel, Monika Szpringer, Jaroslaw Chmielewski, Magdalena Florek-Luszczki
Accumulating evidence indicates that cannabinoid CB1 receptor ligands play a pivotal role in seizures, not only in preclinical studies on animals, but also in clinical settings. This study was aimed at characterizing the influence of arachidonyl-2'-chloroethylamide (ACEA-a selective cannabinoid CB1 receptor agonist) co-administered with phenylmethylsulfonyl fluoride (PMSF) on the anticonvulsant potency of various antiepileptic drugs (clobazam, lacosamide, levetiracetam, phenobarbital, tiagabine and valproate) in the 6-Hz corneal stimulation model...
2017: PloS One
https://www.readbyqxmd.com/read/28854405/newer-antiepileptic-drugs-compared-to-levetiracetam-as-adjunctive-treatments-for-uncontrolled-focal-epilepsy-an-indirect-comparison
#10
Li-Na Zhu, Deng Chen, Da Xu, Ge Tan, Hai-Jiao Wang, Ling Liu
PURPOSE: Newer antiepileptic drugs (AEDs), such as Eslicarbazepine (ESL), Lacosamide (LAC), Perampanel (PER) and Brivaracetam (BRV), have been marketed as adjunctive treatments for partial-onset seizures. Our aim was to compare the efficacy and tolerability of newer AEDs with Levetiracetam (LEV), when used as add-on treatments for uncontrolled focal epilepsy. METHOD: We conducted an online database search on PubMed, Embase, Cochrane Online Library and Clinicaltrials...
August 16, 2017: Seizure: the Journal of the British Epilepsy Association
https://www.readbyqxmd.com/read/28845834/clinical-stabilisation-with-lacosamide-of-mood-disorder-comorbid-with-ptsd-and-fronto-temporal-epilepsy
#11
Ilaria Cuomo, Georgios D Kotzalidis, Sergio De Filippis
BACKGROUND AND AIM OF THE WORK: Mood disorders are often complicated by comorbidity with epilepsy. Anxiety and personality disorders may worsen prognosis and treatment outcome. Lacosamide has been recently introduced as adjunctive treatment for partial epilepsy. Its mechanism consists of selective slow inactivation of voltage-gated sodium channels, thus promoting an extended stabilisation of cell membranes. Antiepileptic drugs have been largely used since the 1950s in psychiatry as mood stabilisers due to their membrane stabilising and anti-kindling effects...
August 23, 2017: Acta Bio-medica: Atenei Parmensis
https://www.readbyqxmd.com/read/28834781/clinical-management-of-elderly-patients-with-epilepsy-the-use-of-lacosamide-in-a-single-center-setting
#12
Sirpa Rainesalo, Jussi Mäkinen, Jani Raitanen, Jukka Peltola
INTRODUCTION: Lacosamide (LCM) is a third-generation antiepileptic drug (AED) for which there is limited experience in the treatment of elderly patients with epilepsy. This study was performed to evaluate the use of LCM in this particular patient group, focusing on its tolerability and effectiveness. This is a retrospective, single-center study, in patients over 60years old treated with LCM between 1/2010 and 5/2015. Altogether, 233 elderly patients receiving LCM were identified; of these, 67 fulfilled the inclusion criteria, i...
August 20, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28833036/treatment-with-lacosamide-impedes-generalized-seizures-in-a-rodent-model-of-cortical-dysplasia
#13
Ashley D Nemes, Rebecca O'Dwyer, Imad M Najm, Zhong Ying, Jorge Gonzalez-Martinez, Andreas V Alexopoulos
OBJECTIVE: Epilepsy is a common neurologic disorder resulting in spontaneous, recurrent seizures. About 30-40% of patients are not responsive to pharmacologic therapies. This may be due to the differences between individual patients such as etiology, underlying pathophysiology, and seizure focus, and it highlights the importance of new drug discovery and testing in this field. Our goal was to determine the efficacy of lacosamide (LCM), a drug approved for the treatment of focal seizures, in a model of generalized epilepsy with cortical dysplasia (CD)...
August 20, 2017: Epilepsia
https://www.readbyqxmd.com/read/28832891/outcome-of-cancer-related-seizures-in-patients-treated-with-lacosamide
#14
M Toledo, A Molins, M Quintana, E Santamarina, F Martinez-Ricarte, E Martínez-Saez, J Salas-Puig
OBJECTIVES: Lacosamide is an antiepileptic drug (AED), which has proven to be effective to control seizures, including acute conditions such as status epilepticus. The aim of this study is to describe the clinical experience with lacosamide in neuro-oncological patients. MATERIALS AND METHODS: Multicenter retrospective study in patients with cancer-related seizures, who received lacosamide as an add-on therapy. RESULTS: Forty-eight patients with benign and malignant tumors, including primary brain tumors, lymphomas, systemic cancer with central nervous system involvement, or paraneoplastic encephalitis, were included...
August 22, 2017: Acta Neurologica Scandinavica
https://www.readbyqxmd.com/read/28810185/outcome-of-treatment-changes-in-patients-with-drug-resistant-chronic-epilepsy-a-tertiary-center-experience
#15
E Martínez-Lizana, F Gil-Lopez, A Donaire, J Aparicio, A Brandt, M Carreño
BACKGROUND: Previous studies suggest that changing patients' anti-epileptic drug regimen can reduce the frequency of seizures. The approval of new anti-epileptic drugs with different modes of action during the last decades has provided multiple options for the treatment of epilepsy, although the efficacy of these new drugs is controversial. We aimed to determine the effects of adding or changing to a previously untried anti-epileptic drug, including recently approved drugs, on the frequency of seizures in patients with drug-resistant epilepsy...
July 29, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28809766/crispr-cas9-editing-of-nf1-gene-identifies-crmp2-as-a-therapeutic-target-in-neurofibromatosis-type-1-nf1-related-pain-that-is-reversed-by-s-lacosamide
#16
Aubin Moutal, Xiaofang Yang, Wennan Li, Kerry B Gilbraith, Shizhen Luo, Song Cai, Liberty François-Moutal, Lindsey A Chew, Seul Ki Yeon, Shreya S Bellampalli, Chaoling Qu, Jennifer Y Xie, Mohab M Ibrahim, May Khanna, Ki Duk Park, Frank Porreca, Rajesh Khanna
Neurofibromatosis type 1 (NF1) is a rare autosomal dominant disease linked to mutations of the Nf1 gene. NF1 patients commonly experience severe pain. Studies on mice with Nf1 haploinsufficiency have been instructive in identifying sensitization of ion channels as a possible cause underlying the heightened pain suffered by NF1 patients. However, behavioral assessments of Nf1+/- mice have led to uncertain conclusions about the potential causal role of Nf1 in pain. We used the clustered regularly interspaced short palindromic repeats/(CRISPR)-associated 9 (CRISPR/Cas9) genome editing system to create and mechanistically characterize a novel rat model of NF1-related pain...
July 3, 2017: Pain
https://www.readbyqxmd.com/read/28804872/lacosamide-in-the-treatment-of-patients-with-epilepsy-and-intellectual-disabilities-a-long-term-study-of-136-patients
#17
Stefan Böttcher, Martin T Lutz, Thomas Mayer
OBJECTIVE: This study aimed to analyze the retention rate of lacosamide (LCM) in patients with epilepsy and intellectual disabilities (IDs), to identify factors influencing retention rate, and to investigate the LCM retention rate with and without concomitant sodium channel blocker (SCB). We hypothesized that the retention rate of LCM with concomitant SCB would be lower than without SCB. METHODS: Using the Kaplan-Meier estimator, we conducted a monocentric, retrospective, observational, open-label study to evaluate LCM retention rates in patients with IDs and drug-resistant epilepsy...
August 14, 2017: Epilepsia
https://www.readbyqxmd.com/read/28799510/safety-profile-of-the-newest-antiepileptic-drugs-a-curated-literature-review
#18
Caterina Palleria, Giuseppe Cozza, Rajeshree Khengar, Vincenzo Libri, Giovambattista De Sarro
BACKGROUND: Despite the introduction of new antiepileptic drugs (AEDs), the quality of life and therapeutic response for patients with epilepsy remain unsatisfactory. In addition, whilst several antiepileptic drugs (AEDs) have been approved and consequently marketed in recent years, little is known about their long-term safety and tolerability. Availability of the newest AEDs, characterized by improved pharmacokinetic profiles, has positively impacted the treatment approach for patients with partial seizures in clinical practice...
August 9, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28757050/electroencephalographic-cognitive-and-neurochemical-effects-of-ly3130481-cerc-611-a-selective-antagonist-of-tarp-%C3%AE-8-associated-ampa-receptors
#19
Jeffrey M Witkin, Jennifer Li, Gary Gilmour, Stephen N Mitchell, Guy Carter, Scott D Gleason, Wesley F Seidel, Brian J Eastwood, Andrew McCarthy, Warren J Porter, Jon Reel, Kevin M Gardinier, Akihiko S Kato, Keith A Wafford
6-[(1S)-1-[1-[5-(2-hydroxyethoxy)-2-pyridyl]pyrazol-3-yl]ethyl]-3H-1,3-benzothiazol-2-one (LY3130481 or CERC-611) is a selective antagonist of AMPA receptors containing transmembrane AMPA receptor regulatory protein (TARP) γ-8. This molecule has been characterized as a potent and efficacious anticonvulsant in an array of acute and chronic epilepsy models in rodents. The present set of experiments was designed to assess the effects of LY3130481 on the electroencephelogram (EEG), cognitive function, and neurochemical outflow...
July 27, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28750560/pharmacokinetic-drug-evaluation-of-lacosamide-for-the-treatment-of-partial-onset-seizures
#20
REVIEW
Stefano de Biase, Mariarosaria Valente, Gian Luigi Gigli, Giovanni Merlino
The goal of pharmacologic therapy with antiepileptic drugs (AEDs) is to reduce the frequency of seizures and achieve a seizure-free state with minimal side effects. However 30% of patients treated with available AEDs continue to experience uncontrolled seizures. There is still need for new AEDs with enhanced effectiveness and tolerability. Areas covered: The present manuscript is based on an extensive Internet and PubMed search from 1992 to 2017. It is focused on the pharmacokinetic properties of lacosamide (LCM) for the treatment of partial-onset seizures...
September 2017: Expert Opinion on Drug Metabolism & Toxicology
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