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Lacosamide for pain

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https://www.readbyqxmd.com/read/27917413/efficacy-of-s-lacosamide-in-preclinical-models-of-cephalic-pain
#1
Aubin Moutal, Nathan Eyde, Edwin Telemi, Ki Duk Park, Jennifer Y Xie, David W Dodick, Frank Porreca, Rajesh Khanna
Migraine is one of the world's most common neurological disorders. Current acute migraine treatments have sub-optimal efficacy and new therapeutic options are needed. Approaches targeting calcitonin gene related peptide (CGRP) signaling are clinically effective but small molecule antagonists have not been advanced due to toxicity. In this study, we explored the axonal growth/specification collapsin response mediator protein 2 (CRMP2) as a novel "druggable" target for inhibiting CGRP release and for potential relevance for treatment of migraine pain...
June 2016: Pain Reports (Baltimore, Md.)
https://www.readbyqxmd.com/read/27363506/efficacy-safety-and-tolerability-of-lacosamide-in-patients-with-gain-of-function-nav1-7-mutation-related-small-fiber-neuropathy-study-protocol-of-a-randomized-controlled-trial-the-lenss-study
#2
Bianca T A de Greef, Ingemar S J Merkies, Margot Geerts, Catharina G Faber, Janneke G J Hoeijmakers
BACKGROUND: Small fiber neuropathy generally leads to considerable pain and autonomic symptoms. Gain-of-function mutations in the SCN9A- gene, which codes for the Nav1.7 voltage-gated sodium channel, have been reported in small fiber neuropathy, suggesting an underlying genetic basis in a subset of patients. Currently available sodium channel blockers lack selectivity, leading to cardiac and central nervous system side effects. Lacosamide is an anticonvulsant, which blocks Nav1.3, Nav1...
June 30, 2016: Trials
https://www.readbyqxmd.com/read/27263827/lacosamide-diminishes-dryness-induced-hyperexcitability-of-corneal-cold-sensitive-nerve-terminals
#3
Illés Kovács, Lóránt Dienes, Kristóf Perényi, Susana Quirce, Carolina Luna, Kamila Mizerska, M Carmen Acosta, Carlos Belmonte, Juana Gallar
Lacosamide is an anti-epileptic drug that is also used for the treatment of painful diabetic neuropathy acting through voltage-gated sodium channels. The aim of this work was to evaluate the effects of acute application of lacosamide on the electrical activity of corneal cold nerve terminals in lacrimo-deficient guinea pigs. Four weeks after unilateral surgical removal of the main lachrimal gland in guinea pigs, corneas were excised and superfused in vitro at 34°C for extracellular electrophysiological recording of nerve terminal impulse activity of cold thermosensitive nerve terminals...
September 15, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/26967696/-s-lacosamide-inhibition-of-crmp2-phosphorylation-reduces-postoperative-and-neuropathic-pain-behaviors-through-distinct-classes-of-sensory-neurons-identified-by-constellation-pharmacology
#4
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
https://www.readbyqxmd.com/read/26916326/-lacosamide-and-neuropathic-pain-a-review
#5
Antonio Alcántara-Montero, Clara I Sánchez-Carnerero
INTRODUCTION: Most of the clinical practice guidelines consulted agree that tricyclics, dual (venlafaxine/duloxetine) antidepressants, gabapentin/pregabalin antiepileptic drugs, lidocaine 5% patches and capsaicin 8% patches are the first-line drugs in the treatment of peripheral neuropathic pain, being tramadol and some strong opioids (morphine, oxycodone and tapentadol) second-line drugs treatment. Moreover, the prevalence of neuropathic pain refractory to treatment is about 1.5% of the population, so that an estimated 50% of patients not responding to prescribed treatment...
March 1, 2016: Revista de Neurologia
https://www.readbyqxmd.com/read/26029937/significant-response-to-lacosamide-in-a-patient-with-severe-chemotherapy-induced-peripheral-neuropathy
#6
Samar A Ibrahim, Zhanna Albany, Constantine Albany
Chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting toxicity of potentially curative cancer therapy regimens. Cisplatin is the class of chemotherapy agent that has a broad spectrum of activity against several solid tumors, but it induces sensory neuropathy of upper and lower extremities. Cisplatin-induced peripheral neuropathy is usually in a "gloves and socks" distribution that can persist for months or years after completion of chemotherapy treatment. If the pain is severe, it affects the patient's long-term quality of life and can potentially result in chemotherapy dose reduction or treatment discontinuation...
May 2015: Journal of Community and Supportive Oncology
https://www.readbyqxmd.com/read/25533381/antinociceptive-effects-of-lacosamide-on-spinal-neuronal-and-behavioural-measures-of-pain-in-a-rat-model-of-osteoarthritis
#7
Wahida Rahman, Anthony H Dickenson
INTRODUCTION: Alterations in voltage-gated sodium channel (VGSC) function have been linked to chronic pain and are good targets for analgesics. Lacosamide (LCM) is a novel anticonvulsant that enhances the slow inactivation state of VGSCs. This conformational state can be induced by repeated neuronal firing and/or under conditions of sustained membrane depolarisation, as is expected for hyperexcitable neurones in pathological conditions such as epilepsy and neuropathy, and probably osteoarthritis (OA)...
2014: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/25479151/pharmacological-management-of-chronic-neuropathic-pain-revised-consensus-statement-from-the-canadian-pain-society
#8
Dwight Moulin, Aline Boulanger, A J Clark, Hance Clarke, Thuan Dao, G A Finley, Andrea Furlan, Ian Gilron, Allan Gordon, Patricia K Morley-Forster, Barry J Sessle, Pamela Squire, Jennifer Stinson, Paul Taenzer, Ana Velly, Mark A Ware, Erica L Weinberg, Owen D Williamson
BACKGROUND: Neuropathic pain (NeP), redefined as pain caused by a lesion or a disease of the somatosensory system, is a disabling condition that affects approximately two million Canadians. OBJECTIVE: To review the randomized controlled trials (RCTs) and systematic reviews related to the pharmacological management of NeP to develop a revised evidence-based consensus statement on its management. METHODS: RCTs, systematic reviews and existing guidelines on the pharmacological management of NeP were evaluated at a consensus meeting in May 2012 and updated until September 2013...
November 2014: Pain Research & Management: the Journal of the Canadian Pain Society
https://www.readbyqxmd.com/read/25418676/chimeric-agents-derived-from-the-functionalized-amino-acid-lacosamide-and-the-%C3%AE-aminoamide-safinamide-evaluation-of-their-inhibitory-actions-on-voltage-gated-sodium-channels-and-antiseizure-and-antinociception-activities-and-comparison-with-lacosamide-and-safinamide
#9
COMPARATIVE STUDY
Ki Duk Park, Xiao-Fang Yang, Erik T Dustrude, Yuying Wang, Matthew S Ripsch, Fletcher A White, Rajesh Khanna, Harold Kohn
The functionalized amino acid, lacosamide ((R)-2), and the α-aminoamide, safinamide ((S)-3), are neurological agents that have been extensively investigated and have displayed potent anticonvulsant activities in seizure models. Both compounds have been reported to modulate voltage-gated sodium channel activity. We have prepared a series of chimeric compounds, (R)-7-(R)-10, by merging key structural units in these two clinical agents, and then compared their activities with (R)-2 and (S)-3. Compounds were assessed for their ability to alter sodium channel kinetics for inactivation, frequency (use)-dependence, and steady-state activation and fast inactivation...
February 18, 2015: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/25245872/-effectiveness-of-lacosamide-in-the-treatment-of-refractory-neuropathic-pain-an-open-observational-trial
#10
MULTICENTER STUDY
José M Gómez-Argüelles, Pedro E Bermejo, Manuel Lara, Jerónimo Almajano, Esther Aragón, Fernando García del Carrizo, M Victoria Blanco, Francisco J Valenzuela-Rojas, Juan Colás, Octavio Sánchez-Del Valle, M Ángeles Ceballos, M Elena Toribio-Díaz, Germán Latorre-González, Lucienne Costa-Frossard, M del Mar Morin-Martin
INTRODUCTION: Although different treatments are available for neuropathic pain, these patients are often refractory, which makes it necessary to test treatments that, as they have proven useful in other pathologies, could be effective in neuropathic pain. PATIENTS AND METHODS: The study made use of the medical records of patients who had been treated with lacosamide for neuropathic pain in different hospitals in the central area of the peninsula and who fulfilled similar characteristics in terms of refractoriness to other standard treatments, in a follow-up that lasted at least six months, or who had had to stop treatment with that drug for some reason or another...
October 1, 2014: Revista de Neurologia
https://www.readbyqxmd.com/read/25196459/pharmacokinetic-and-pharmacodynamic-interactions-between-antiepileptics-and-antidepressants
#11
REVIEW
Domenico Italiano, Edoardo Spina, Jose de Leon
INTRODUCTION: Antiepileptic-antidepressant combinations are frequently used by clinicians; their pharmacokinetic (PK) and pharmacodynamic (PD) drug interactions (DIs) have not been well studied but are frequently likely to be clinically relevant. AREAS COVERED: This article provides a comprehensive review of PK DIs between antiepileptics and antidepressants. In the absence of PD DI studies, PD information on pharmacological mechanisms and studies on efficacy and safety of individual drugs are reviewed...
November 2014: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/24217986/antiepileptic-drugs-for-neuropathic-pain-and-fibromyalgia-an-overview-of-cochrane-reviews
#12
REVIEW
Philip J Wiffen, Sheena Derry, R Andrew Moore, Dominic Aldington, Peter Cole, Andrew S C Rice, Michael P T Lunn, Katri Hamunen, Maija Haanpaa, Eija A Kalso
BACKGROUND: Antiepileptic drugs have been used for treating different types of neuropathic pain, and sometimes fibromyalgia. Our understanding of quality standards in chronic pain trials has improved to include new sources of potential bias. Individual Cochrane reviews using these new standards have assessed individual antiepileptic drugs. An early review from this group, originally published in 1998, was titled 'Anticonvulsants for acute and chronic pain'. This overview now covers the neuropathic pain aspect of that original review, which was withdrawn in 2009...
November 11, 2013: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/24203890/lacosamide-a-review-of-its-use-as-adjunctive-therapy-in-the-management-of-partial-onset-seizures
#13
REVIEW
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
https://www.readbyqxmd.com/read/24129853/anticonvulsants-for-fibromyalgia
#14
REVIEW
Nurcan Üçeyler, Claudia Sommer, Brian Walitt, Winfried Häuser
BACKGROUND: Fibromyalgia (FM) is a clinically well-defined chronic condition of unknown aetiology characterised by chronic widespread pain that often co-exists with sleep problems and fatigue. People often report high disability levels and poor health-related quality of life (HRQoL). Drug therapy focuses on reducing key symptoms and disability, and improving HRQoL. Anticonvulsants (antiepileptic drugs) are drugs frequently used for the treatment of chronic pain syndromes. OBJECTIVES: To assess the benefits and harms of anticonvulsants for treating FM symptoms...
2013: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/24052442/-lacosamide-as-an-alternative-in-the-treatment-of-post-surgery-neuropathic-pain-in-an-allergic-patient
#15
María Estefanía Monge-Márquez, Javier Márquez-Rivas, María José Mayorga-Buiza, Mónica Rivero-Garvía
INTRODUCTION: Neuropathic pain is a condition that is still not well understood, although it affects a significantly high percentage of the population. The main problem lies in the fact that it can become a fairly disabling pathology. The most frequent treatment is based essentially on two drugs: gabapentin and pregabalin. Other pharmaceuticals, such as antidepressants, opioids or N-methyl-D-aspartate receptor antagonists can also be employed in combination with the primary drugs. All the same, treatment remains unsatisfactory...
October 1, 2013: Revista de Neurologia
https://www.readbyqxmd.com/read/23931787/management-of-painful-neuropathies
#16
REVIEW
Nanna Brix Finnerup, Søren Hein Sindrup, Troels Staehelin Jensen
Neuropathic pain is the most common type of pain in neuropathy. In painful polyneuropathies the pain usually has a "glove and stocking" distribution. The pain may be predominantly spontaneous, e.g., with a burning, pricking, or shooting character or characterized by evoked pain such as mechanical or cold allodynia. In the clinical setting, the prevention of painful neuropathies and treatment of underlying neuropathy remains inadequate and thus symptomatic treatment of the pain and related disability needs to be offered...
2013: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/23672271/anti-epileptic-drugs-for-pain-271
#17
REVIEW
Seth Hepner, René Claxton
TCAs, SNRIs, and the AEDs gabapentin and pregabalin are the best adjuvant analgesics for neuropathic pain. For patients who are intolerant to or who experience pain unresponsive to the above medications, one can consider therapy with carbamazepine, oxcarbazepine, valproic acid, topiramate, or lacosamide. However, as these agents are associated with more side effects and lower rates of efficacy, expert consultation is strongly recommended.
July 2013: Journal of Palliative Medicine
https://www.readbyqxmd.com/read/23229998/analgesic-ineffectiveness-of-lacosamide-after-spinal-nerve-ligation-and-its-sodium-channel-activity-in-injured-neurons
#18
T Hagenacker, N Schäfer, D Büsselberg, M Schäfers
BACKGROUND: Lacosamide is a novel anti-epileptic drug that enhances the slow- and not fast-inactivating state of voltage-gated sodium channels. Lacosamide has demonstrated analgesic efficacy in several animal studies but preclinical studies on neuropathic pain models are rare, and recent clinical trials showed no superior analgesic effects. METHODS: Here, we examine whether an acute or chronic administration of lacosamide (3-60 mg/kg, i.p.) attenuates pain behaviour induced by spinal nerve ligation (SNL)...
July 2013: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/22779776/the-adverse-event-profile-of-lacosamide-a-systematic-review-and-meta-analysis-of-randomized-controlled-trials
#19
REVIEW
Gaetano Zaccara, Piero Perucca, Giulia Loiacono, Fabio Giovannelli, Alberto Verrotti
PURPOSE: Defining the tolerability and safety profile of recently marketed antiepileptic drugs, such as lacosamide (LCM), is a prerequisite for their optimal utilization in clinical practice. We aimed to identify any adverse event (AE) associated with LCM treatment by conducting a systematic review and meta-analysis of all available randomized controlled trials (RCTs). We also evaluated the association of serious AEs with LCM, the proportion of study withdrawals due to intolerable AEs at different LCM doses, and whether the tolerability profile of LCM differs according to the disorder in which it was investigated...
January 2013: Epilepsia
https://www.readbyqxmd.com/read/22575571/the-differential-effects-of-two-sodium-channel-modulators-on-the-conductive-properties-of-c-fibers-in-pig-skin-in-vivo
#20
Otilia Obreja, Michael Hirth, Brian Turnquist, Roman Rukwied, Matthias Ringkamp, Martin Schmelz
BACKGROUND: Axonal sodium channels are attractive targets for chronic pain treatment, and recent evidence suggests that specific targeting of the slow inactivation of sodium channels (NaV) might exert analgesic effects. Using a human-like animal model, the pig, we compared changes in the conductive properties of different C-fiber classes on acute administration of lidocaine (nonselective NaV blocker) and lacosamide (selective enhancer of NaV slow inactivation). METHODS: Single-fiber extracellular recordings from saphenous nerves were performed...
September 2012: Anesthesia and Analgesia
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