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I N Vakula, E O Boiko, Yu A Vorona, Ya A Storozhuk, E Yu Nikiforova, D I Nikiforova, E Yu Mel'nik
OBJECTIVE: To evaluate the efficacy and tolerability of intravenous lacosamide (vimpat) in inpatients with frequent partial-onset seizures and affective and cognitive disorders. MATERIAL AND METHODS: Fifteen patients were enrolled including 14 patients diagnosed with «organic personality disorder associated with epilepsy» (cryptogenic or symptomatic epilepsy with frequent partial-onset and/or secondary-generalized seizures (serial seizures in some cases) and 1 patient with a preliminary diagnosis of «organic schizophrenia-like disorder», which was changed for «organic personality disorder associated with epilepsy» after examination...
2016: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
Aubin Moutal, Lindsey A Chew, Xiaofang Yang, Yue Wang, Seul Ki Yeon, Edwin Telemi, Seeneen Meroueh, Ki Duk Park, Raghuraman Shrinivasan, Kerry B Gilbraith, Chaoling Qu, Jennifer Y Xie, Amol Patwardhan, Todd W Vanderah, May Khanna, Frank Porreca, Rajesh Khanna
Chronic pain affects the life of millions of people. Current treatments have deleterious side effects. We have advanced a strategy for targeting protein interactions which regulate the N-type voltage-gated calcium (CaV2.2) channel as an alternative to direct channel block. Peptides uncoupling CaV2.2 interactions with the axonal collapsin response mediator protein 2 (CRMP2) were antinociceptive without effects on memory, depression, and reward/addiction. A search for small molecules that could recapitulate uncoupling of the CaV2...
July 2016: Pain
Lesley J Scott
Lacosamide (Vimpat(®)) is a functionalized amino acid available orally (as a solution or tablets) and as an intravenous infusion for use as monotherapy (only in the USA) or adjunctive therapy for the treatment of focal seizures in adult and adolescent (aged ≥17 years in the USA) patients with epilepsy. As adjunctive therapy to other antiepileptic drugs (AEDs), lacosamide provided effective seizure control and was generally well tolerated in adults and adolescents (aged ≥16 years) in randomized clinical trials and in the real-world setting...
December 2015: Drugs
Aubin Moutal, Liberty François-Moutal, Samantha Perez-Miller, Karissa Cottier, Lindsey Anne Chew, Seul Ki Yeon, Jixun Dai, Ki Duk Park, May Khanna, Rajesh Khanna
The neuronal circuit remodels during development as well as in human neuropathologies such as epilepsy. Neurite outgrowth is an obligatory step in these events. We recently reported that alterations in the phosphorylation state of an axon specification/guidance protein, the collapsin response mediator protein 2 (CRMP2), play a major role in the activity-dependent regulation of neurite outgrowth. We also identified (S)-LCM, an inactive stereoisomer of the clinically used antiepileptic drug (R)-LCM (Vimpat®), as a novel tool for preferentially targeting CRMP2-mediated neurite outgrowth...
April 2016: Molecular Neurobiology
Sarah M Wilson, Aubin Moutal, Ohannes K Melemedjian, Yuying Wang, Weina Ju, Liberty François-Moutal, May Khanna, Rajesh Khanna
Activity-dependent neurite outgrowth is a highly complex, regulated process with important implications for neuronal circuit remodeling in development as well as in seizure-induced sprouting in epilepsy. Recent work has linked outgrowth to collapsin response mediator protein 2 (CRMP2), an intracellular phosphoprotein originally identified as axon guidance and growth cone collapse protein. The neurite outgrowth promoting function of CRMP2 is regulated by its phosphorylation state. In this study, depolarization (potassium chloride)-driven activity increased the level of active CRMP2 by decreasing its phosphorylation by GSK3β via a reduction in priming by Cdk5...
2014: Frontiers in Cellular Neuroscience
Sarah M Wilson, Rajesh Khanna
The novel antiepileptic drug lacosamide (LCM; SPM927, Vimpat®) has been heralded as having a dual-mode of action through interactions with both the voltage-gated sodium channel and the neurite outgrowth-promoting collapsin response mediator protein 2 (CRMP2). Lacosamide's ability to dampen neuronal excitability through the voltage-gated sodium channel likely underlies its efficacy in attenuating the symptoms of epilepsy (i.e., seizures). While the role of CRMP2 in epilepsy has not been well studied, given the proposed involvement of circuit reorganization in epileptogenesis, the ability of lacosamide to alter CRMP2 function may prove disease modifying...
April 2015: Molecular Neurobiology
A Pitkänen, R Immonen, X Ndode-Ekane, O Gröhn, T Stöhr, J Nissinen
In a subgroup of patients, traumatic brain injury (TBI) results in the occurrence of acute epileptic seizures or even status epilepticus, which are treated with antiepileptic drugs (AEDs). Recent experimental data, however, suggest that administration of AEDs at the early post-injury phase can compromise the recovery process. The present study was designed to assess the profile of a novel anticonvulsant, lacosamide (Vimpat) on post-TBI structural, motor and cognitive outcomes. Moderate TBI was induced by lateral fluid-percussion injury in adult rats...
May 2014: Epilepsy Research
Sheridan M Hoy
Lacosamide (Vimpat(®)) is a functionalized amino acid available orally (as a syrup or tablet) and as an intravenous infusion. It is believed to exert its antiepileptic effect by selectively enhancing the slow inactivation of voltage-gated sodium channels. Lacosamide is approved in several countries worldwide as an adjunctive therapy for the treatment of partial-onset seizures; however, prescribing regulations differ between countries. This article reviews the use of lacosamide as indicated in adults and adolescents (aged 16-18 years) in the EU, where it is approved in this patient population as an adjunctive therapy to other AEDs in the treatment of partial-onset seizures, with or without secondary generalization...
December 2013: CNS Drugs
Alexey Shandra, Pavel Shandra, Olga Kaschenko, Alain Matagne, Thomas Stöhr
PURPOSE: Lacosamide (LCM, Vimpat) is an anticonvulsant with a unique mode of action. This provides lacosamide with the potential to act additively or even synergistically with other antiepileptic drugs (AEDs). The objective of this study was to determine the presence of such interactions by isobolographic analysis. METHODS: The anticonvulsant effect of LCM in combination with other AEDs including carbamazepine (CBZ), phenytoin (PHT), valproate (VPA), lamotrigine (LTG), topiramate (TPM), gabapentin (GBP), and levetiracetam (LEV) at fixed dose ratios of 1:3, 1:1, and 3:1, was evaluated in the 6-Hz-induced seizure model in mice...
July 2013: Epilepsia
Carlos Casas-Fernández, Antonio Martínez-Bermejo, Miguel Rufo-Campos, Patricia Smeyers-Durá, José L Herranz-Fernández, Salvador Ibáñez-Micó, Jaume Campistol-Plana, Helena Alarcón-Martínez, Jaime Campos-Castelló
BACKGROUND: The safety and effectiveness of lacosamide, an antiepileptic drug (AED) that selectively enhances the slow inactivation of voltage-gated sodium channels without affecting rapid inactivation, has been demonstrated in randomized, double-blind, placebo-controlled trials in adults with focal epileptic seizures. Although lacosamide is approved for use in patients over 16 years of age, limited clinical experience exists for younger patients. OBJECTIVE: To assess the efficacy and tolerability of lacosamide in children with refractory epilepsy...
December 1, 2012: Drugs in R&D
A S Petrukhin, K V Voronkova, O A Pylaeva
The new antiepileptic drug (AED) lacosamide (vimpat, "UCB Pharma") with a new mechanism of action was registered in Russia in 2010. The drug should be used as add-on treatment in patients over 16 years and older with non-controlled focal seizures with- or without secondary localization. The authors review the data of literature and the results of trials on efficacy and safety of lacosamide for peroral and intravenous introduction. Randomized clinical trials of the peroral form of this drug provide evidence that lacosamide is a prospective preparation for complex treatment of drug-resistant epilepsy in the view of its safety and tolerability...
2012: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
Christian Wolff, Bruce Carrington, Michel Varrin-Doyer, Anne Vandendriessche, Christy Van der Perren, Michel Famelart, Michel Gillard, Patrik Foerch, Véronique Rogemond, Jerôme Honnorat, Alastair Lawson, Karen Miller
AIMS: Lacosamide (LCM; SPM 927, Vimpat®) is an antiepileptic drug (AED) used as adjunctive treatment for adults with partial-onset seizures. LCM has a different mode of action from traditional sodium channel blocking AEDs in that it selectively enhances slow inactivation of sodium channels without affecting fast inactivation. Initial investigations suggested that LCM might have an additional mode of action by binding to the collapsin response mediator protein 2 (CRMP-2), which is further investigated here...
June 2012: CNS Neuroscience & Therapeutics
C Kestelyn, M Lastelle, N Higuet, S Dell'Aiera, L Staelens, P Boulanger, H Boekens, S Smith
Lacosamide (Vimpat®) is an antiepileptic drug approved in the USA, Europe and several other countries as adjunctive therapy for partial-onset seizures. We report a simple HPLC method with UV detection for the quantification of lacosamide in human plasma. The method involves protein precipitation with methanol followed by chromatographic separation using an ACE® C18-AR column (2.1 mm × 150 mm, 3.0 µm) and mobile phases consisting of mixtures of ammonium formate buffer at pH 9 and acetonitrile. Briefly, 25 µl of internal standard and 300 µl of methanol are added to 100 µl of plasma...
November 2011: Bioanalysis
Yuying Wang, Ki Duk Park, Christophe Salome, Sarah M Wilson, James P Stables, Rihe Liu, Rajesh Khanna, Harold Kohn
The novel antiepileptic drug, (R)-N-benzyl 2-acetamido-3-methoxypropionamide ((R)-lacosamide, Vimpat(®) ((R)-1)), was recently approved in the US and Europe for adjuvant treatment of partial-onset seizures in adults. (R)-1 preferentially enhances slow inactivation of voltage-gated Na(+) currents, a pharmacological process relevant in the hyperexcitable neuron. We have advanced a strategy to identify lacosamide binding partners by attaching affinity bait (AB) and chemical reporter (CR) groups to (R)-1 to aid receptor detection and isolation...
February 16, 2011: ACS Chemical Neuroscience
L R Zenkov
No abstract text is available yet for this article.
2010: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
Daniel Duh, Sandrine Peeters
No abstract text is available yet for this article.
March 2011: Journal de Pharmacie de Belgique
John-Kenneth Sake, David Hebert, Jouko Isojärvi, Pamela Doty, Marc De Backer, Kendra Davies, Andrea Eggert-Formella, James Zackheim
BACKGROUND: Lacosamide, a new antiepileptic drug (AED) with a different pharmacological action that enhances sodium channel slow inactivation, is approved for the adjunctive treatment of partial-onset seizures in adults. Previous analyses of pooled phase II/III trials have demonstrated that lacosamide provides additional efficacy when added to a broad range of AEDs. OBJECTIVE: To further evaluate the efficacy and safety of lacosamide by grouping patients based upon the sodium channel-blocking properties of their concomitant AEDs...
December 2010: CNS Drugs
Steve Chung, Elinor Ben-Menachem, Michael R Sperling, William Rosenfeld, Nathan B Fountain, Selim Benbadis, David Hebert, Jouko Isojärvi, Pamela Doty
BACKGROUND: Lacosamide is an antiepileptic drug (AED) approved for the adjunctive treatment of partial-onset seizures in adults. Completed phase II/III clinical trials of lacosamide provide a valuable opportunity to evaluate clinically relevant aspects of the resulting large patient pool. OBJECTIVE: To provide insight into the clinical utility of lacosamide by performing a priori-defined and post hoc analyses on a large, pooled patient population. STUDY DESIGN: Pooled data from three randomized, double-blind, multicentre, placebo-controlled phase II/III trials...
December 2010: CNS Drugs
Guy A Higgins, Nathalie Breysse, Elijus Undzys, Calvin Kuo, Narges Joharchi, D Richard Derksen, Tao Xin, Methvin Isaac, Malik Slassi
Lacosamide ((R)-2-acetamido-N-benzyl-3-methoxypropionamide; formerly harkoseride, SPM 927; Vimpat), has been recently approved by US and European regulatory authorities for use as add-on therapy for partial-onset seizures in adults. Because a number of anti-epileptic drugs are used to treat conditions beyond epilepsy, including anxiety, in the present study we investigated the anxiolytic potential of lacosamide in a conditioned emotional response (CER) model in rat, and the mouse marble burying assay. In each test lacosamide produced a significant effect consistent with anxiolysis, i...
December 10, 2009: European Journal of Pharmacology
Christian Tilz, Roland Resch, Thomas Hofer, Christian Eggers
Lacosamide (Vimpat) is a newly licensed novel antiepileptic drug. We report a case of refractory convulsive status epilepticus (CSE) that was successfully controlled with lacosamide. The 38-year-old male patient was admitted for a series of complex partial seizures with secondary generalization leading to refractory CSE. During the transport to the hospital the patient was given 22.5 mg diazepam, 12.5 mg etomidate, and 5 mg midazolam without success. An additional dose of 4 mg lorazepam and a dose of 1,500 mg levetiracetam after admission were yet without clinical effect...
February 2010: Epilepsia
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