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https://www.readbyqxmd.com/read/29045303/riluzole-serum-concentration-in-pediatric-patients-treated-for-obsessive-compulsive-disorder
#1
Paul Grant, Cristan Farmer, Jane Song, Timothy Kish, Susan Swedo
PURPOSE/BACKGROUND: The goals of this study were to determine whether pediatric serum concentration of riluzole is similar to that observed in adults and to determine whether riluzole serum concentration is associated with adverse effects or efficacy in children and adolescents with treatment-refractory obsessive-compulsive disorder. METHODS/PROCEDURES: Data were drawn from previously published studies: 1 open-label trial and 1 randomized controlled trial with an open-label extension phase...
October 17, 2017: Journal of Clinical Psychopharmacology
https://www.readbyqxmd.com/read/29033893/shortcomings-in-the-current-amyotrophic-lateral-sclerosis-trials-and-potential-solutions-for-improvement
#2
REVIEW
Nakul Katyal, Raghav Govindarajan
Amyotrophic lateral sclerosis (ALS) is a clinically progressive neurodegenerative syndrome predominantly affecting motor neurons and their associated tracts. Riluzole and edaravone are the only FDA certified drugs for treating ALS. Over the past two decades, almost all clinical trials aiming to develop a successful therapeutic strategy for this disease have failed. Genetic complexity, inadequate animal models, poor clinical trial design, lack of sensitive biomarkers, and diagnostic delays are some of the potential reasons limiting any significant development in ALS clinical trials...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/29031901/als-and-ftd-insights-into-the-disease-mechanisms-and-therapeutic-targets
#3
Rajka M Liscic
Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are neurodegenerative disorders, related by signs of deteriorating motor and cognitive functions, and short survival. The causes are still largely unknown and no effective treatment currently exists. It has been shown that FTLD may coexist with ALS. The overlap between ALS and frontotemporal dementia (FTD), the clinical syndrome associated with FTLD, occurs at clinical, genetic, and pathological levels. The hallmark proteins of the pathognomonic inclusions are SOD-1, TDP-43 or FUS, rarely the disease is caused by mutations in the respective genes...
October 11, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28990593/riluzole-impairs-cocaine-reinstatement-and-restores-adaptations-in-intrinsic-excitability-and-glt-1-expression
#4
Marian T Sepulveda-Orengo, Kati L Healey, Ronald Kim, Alyson C Auriemma, Jennifer Rojas, Nicholas Woronoff, Rachel Hyppolite, Kathryn J Reissner
Adaptations in glutamate signaling within the brain's reward circuitry are observed following withdrawal from several abused drugs, including cocaine. These include changes in intrinsic cellular excitability, glutamate release, and glutamate uptake. Pharmacological or optogenetic reversal of these adaptations have been shown to reduce measures of cocaine craving and seeking, raising the hypothesis that regulation of glutamatergic signaling represents a viable target for the treatment of substance use disorders...
October 9, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28953220/genetic-association-between-amyotrophic-lateral-sclerosis-and-cancer
#5
Y-H Taguchi, Hsiuying Wang
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. An ALS drug, Riluzole, has been shown to induce two different anticancer effects on hepatocellular carcinoma (HCC). In light of this finding, we explore the relationship between ALS and cancer, especially for HCC, from the molecular biological viewpoint. We establish biomarkers that can discriminate between ALS patients and healthy controls. A principal component analysis (PCA) based unsupervised feature extraction (FE) is used to find gene biomarkers of ALS based on microarray gene expression data...
September 27, 2017: Genes
https://www.readbyqxmd.com/read/28939972/effects-of-benzothiazolamines-on-voltage-gated-sodium-channels
#6
Alessandro Farinato, Concetta Altamura, Jean-François Desaphy
Benzothiazole is a versatile fused heterocycle that aroused much interest in drug discovery as anticonvulsant, neuroprotective, analgesic, anti-inflammatory, antimicrobial, and anticancer. Two benzothiazolamines, riluzole and lubeluzole, are known blockers of voltage-gated sodium (Nav) channels. Riluzole is clinically used as a neuroprotectant in amyotrophic lateral sclerosis. Inhibition of Nav channels by riluzole is voltage-dependent due to preferential binding to inactivated sodium channels. Yet the drug exerts little use-dependent block, probably because it lacks protonable amine...
September 23, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28936176/chronic-intermittent-hypoxia-differentially-impacts-different-states-of-inspiratory-activity-at-the-level-of-the-preb%C3%A3-tzinger-complex
#7
Alfredo J Garcia, Tatiana Dashevskiy, Maggie A Khuu, Jan-Marino Ramirez
The preBötzinger complex (preBötC) is a medullary brainstem network crucially involved in the generation of different inspiratory rhythms. In the isolated brainstem slice, the preBötC reconfigures to produce different rhythms that we refer to as "fictive eupnea" under baseline conditions (i.e., carbogen), and "fictive gasping" in hypoxia. We recently demonstrated that fictive eupnea is irregular following exposure to chronic intermittent hypoxia (CIH). However, it is unknown how CIH impacts fictive gasping...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28922069/glutamatergic-agents-in-the-treatment-of-compulsivity-and-impulsivity-in-child-and-adolescent-psychiatry-a-systematic-review-of-the-literature
#8
Konstantin Mechler, Alexander Häge, Nina Schweinfurth, Jeffrey C Glennon, Rick M Dijkhuizen, Declan Murphy, Sarah Durston, Steven Williams, Jan K Buitelaar, Tobias Banaschewski, Ralf W Dittmann, The Tactics Consortium
OBJECTIVE: Research has implicated glutamatergic projections between the various frontal subregions in the pathogenesis of compulsivity and impulsivity. Reducing striatal glutamate release, or antagonising the action of glutamate at its receptors, may therefore represent viable treatment strategies. Several glutamatergic agents with regulatory approval for other indications are available and may be of potential benefit in the treatment of compulsivity/impulsivity in psychiatric disorders in paediatric patients...
September 18, 2017: Zeitschrift Für Kinder- und Jugendpsychiatrie und Psychotherapie
https://www.readbyqxmd.com/read/28917164/uplc-ms-ms-assay-of-riluzole-in-human-plasma-and-cerebrospinal-fluid-csf-application-in-samples-from-spinal-cord-injured-patients
#9
Mahua Sarkar, Robert G Grossman, Elizabeth G Toups, Diana S-L Chow
In the present study, a sensitive and robust LC-MS/MS method has been developed and validated for the quantification of riluzole in human plasma and cerebrospinal fluid (CSF) in clinical samples from patients with spinal cord injury (SCI). Riluzole and its labeled internal standard (IS) were isolated from plasma and CSF by liquid-liquid extraction using ethyl acetate. Riluzole (m/z 235→166) and IS (m/z 238→169) were detected by electrospray ionization (ESI) using multiple reaction monitoring (MRM) in a positive mode...
September 1, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28873374/characteristics-and-prognosis-of-oldest-old-subjects-with-amyotrophic-lateral-sclerosis
#10
Meira Dandaba, Philippe Couratier, Anaïs Labrunie, Marie Nicol, Bello Hamidou, Marie Raymondeau, Giancarlo Logroscino, Pierre Marie Preux, Benoît Marin
BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is an age-related neurodegenerative disease with unclear characteristics and prognosis in the oldest old (80 years and over). The aim of this study was to compare the oldest old and younger ALS patients in terms of clinical and socio-demographic characteristics, and prognosis. METHODS: ALS incident cases from the register of ALS in Limousin (FRALim), diagnosed between January 2000 and July 2013, were included. Descriptive and comparative analyses by age group were carried out...
2017: Neuroepidemiology
https://www.readbyqxmd.com/read/28872912/an-assessment-of-treatment-guidelines-clinical-practices-demographics-and-progression-of-disease-among-patients-with-amyotrophic-lateral-sclerosis-in-japan-the-united-states-and-europe
#11
Koji Takei, Kikumi Tsuda, Fumihiro Takahashi, Manabu Hirai, Joseph Palumbo
BACKGROUND: There is an increasing clinical research focus on neuroprotective agents in amyotrophic lateral sclerosis (ALS). However, it is unclear how generalisable clinical study trial results are between different countries and regions. OBJECTIVE: To assess similarities and differences in clinical practice and treatment guidelines for ALS, and also to compare the demographics and rate of progression of disease in patients with ALS enrolled in clinical trials in Japan, the US, and Europe...
October 2017: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration
https://www.readbyqxmd.com/read/28872909/introduction-to-supplement-the-current-status-of-treatment-for-als
#12
Robert G Miller, Stanley H Appel
ALS is a lethal neurodegenerative disease wherein the diagnosis is often delayed. Our understanding of the pathobiology is slowly expanding, and the number of new genes is rapidly increasing. The development of potential treatments targeting specific mechanisms is beginning to offer hope. Evidence-based treatments and the development of quality measures have raised the standard of care. The current status of treatment for ALS includes one drug riluzole that slows progression modestly, and another drug edaravone that was recently approved by FDA to slow ALS progression...
October 2017: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration
https://www.readbyqxmd.com/read/28867362/riluzole-induced-recurrent-pancreatitis
#13
Catarina Falcão de Campos, Mamede de Carvalho
Riluzole is the only drug approved for the treatment of patients with Amyotrophic Lateral Sclerosis (ALS). It is well tolerated, being the most frequent adverse effects asthenia, nausea and reversible increase of liver enzymes levels. Severe adverse effects are extremely rare. We report for the first time, two patients with sporadic limb-onset ALS who developed recurrent acute pancreatitis (AP), with portal vein thrombosis as complication, during treatment with riluzole. We suggest that AP should be considered asa probable rare and severe side effect of treatment with riluzole in patients with ALS...
November 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/28851920/excessive-spinal-glutamate-transmission-is-involved-in-oxaliplatin-induced-mechanical-allodynia-a-possibility-for-riluzole-as-a-prophylactic-drug
#14
Shota Yamamoto, Soichiro Ushio, Nobuaki Egashira, Takehiro Kawashiri, Shohei Mitsuyasu, Hitomi Higuchi, Nana Ozawa, Ken Masuguchi, Yuko Ono, Satohiro Masuda
Oxaliplatin, a chemotherapy medication, causes severe peripheral neuropathy. Although oxaliplatin-induced peripheral neuropathy is a dose-limiting toxicity, a therapeutic strategy against its effects has not been established. We previously reported the involvement of N-methyl-D-aspartate receptors and their intracellular signalling pathway in oxaliplatin-induced mechanical allodynia in rats. The aim of this study was to clarify the involvement of spinal glutamate transmission in oxaliplatin-induced mechanical allodynia...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28844763/hyperexcitability-in-synaptic-and-firing-activities-of-spinal-motoneurons-in-an-adult-mouse-model-of-amyotrophic-lateral-sclerosis
#15
Mingchen C Jiang, Adesoji Adimula, Derin Birch, Charles J Heckman
Hyperexcitability is hypothesized to contribute to the degeneration of spinal motoneurons (MNs) in amyotrophic lateral sclerosis (ALS). Studies, thus far, have not linked hyperexcitability to the intrinsic properties of MNs in the adult ALS mouse model with the G93A-mutated SOD1 protein (mSOD1(G93A)). In this study, we obtained two types of measurements: ventral root recordings to assess motor output and intracellular recordings to assess synaptic properties of individual MNs. All studies were carried out in an in vitro preparation of the sacral spinal cords of mSOD1(G93A) mice and their non-transgenic (NT) littermates, both in the age range of 50-90days...
October 24, 2017: Neuroscience
https://www.readbyqxmd.com/read/28843863/administration-of-riluzole-to-the-basolateral-amygdala-facilitates-fear-extinction-in-rats
#16
Azusa Sugiyama, Misa Yamada, Akiyoshi Saitoh, Jun-Ichiro Oka, Mitsuhiko Yamada
A general understanding exists that inhibition of glutamatergic neurotransmission in the basolateral amygdala (BLA) impairs fear extinction in rodents. Surprisingly, we recently found that systemic administration of riluzole, which has been shown to inhibit the glutamatergic system, facilitates extinction learning in rats with a preconditioned contextual fear response. However, the mechanisms underlying this paradoxical effect of riluzole remain unclear. In this study, adult male Wistar rats were bilaterally cannulated in the BLA to examine the effects of intra-BLA administration of riluzole...
January 15, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/28828613/glutamate-transport-system-as-a-novel-therapeutic-target-in-chronic-pain-molecular-mechanisms-and-pharmacology
#17
Georgi Gegelashvili, Ole Jannik Bjerrum
The vast majority of peripheral neurons sensing noxious stimuli and conducting pain signals to the dorsal horn of the spinal cord utilize glutamate as a chemical transmitter of excitation. High-affinity glutamate transporter subtypes GLAST/EAAT1, GLT1/EAAT2, EAAC1/EAAT3, and EAAT4, differentially expressed on sensory neurons, postsynaptic spinal interneurons, and neighboring glia, ensure fine modulation of glutamate neurotransmission in the spinal cord. The glutamate transport system seems to play important roles in molecular mechanisms underlying chronic pain and analgesia...
2017: Advances in Neurobiology
https://www.readbyqxmd.com/read/28817498/an-interprofessional-approach-to-amyotrophic-lateral-sclerosis-care
#18
Jerri L Jaffa, Marlene Dufault, Mary Lavin
Amyotrophic lateral sclerosis (ALS) is a progressive fatal neurodegenerative disease that is characterized by the death of motor neurons in the spinal cord, brain stem, and motor cortex that are responsible for voluntary movement. For unknown reasons, military veterans are approximately twice as likely as the public to be given a diagnosis of ALS. Currently, there is no cure for ALS. The only US Food and Drug Administration-approved disease-modifying medication is riluzole (Rilutek), which may slow ALS progression but only minimally increases survival time...
August 16, 2017: Journal of Neuroscience Nursing: Journal of the American Association of Neuroscience Nurses
https://www.readbyqxmd.com/read/28813081/epidemiological-and-clinical-factors-impact-on-the-benefit-of-riluzole-in-the-survival-rates-of-patients-with-als
#19
Francis Meire Fávero, Mariana Callil Voos, Isac de Castro, Fátima Aparecida Caromano, Acary Souza Bulle Oliveira
Objective: To investigate the impact of epidemiological and clinical factors on the benefit of riluzole in patients with amyotrophic lateral sclerosis (ALS). Methods: The survival rate of 578 patients with ALS (1999-2011) was analyzed by descriptive statistics and Kaplan-Meier curves. Considering the median of the sample survival time (19 months), patients were divided in two groups: below (B19) and above the median (A19). Kaplan-Meier curves compared the survival rates of patients treated with riluzole and with patients who did not take the medication...
August 2017: Arquivos de Neuro-psiquiatria
https://www.readbyqxmd.com/read/28801400/protein-misfolding-amyotrophic-lateral-sclerosis-and-guanabenz-protocol-for-a-phase-ii-rct-with-futility-design-promise-trial
#20
Eleonora Dalla Bella, Irene Tramacere, Giovanni Antonini, Giuseppe Borghero, Margherita Capasso, Claudia Caponnetto, Adriano Chiò, Massimo Corbo, Roberto Eleopra, Massimiliano Filosto, Fabio Giannini, Enrico Granieri, Vincenzo La Bella, Christian Lunetta, Jessica Mandrioli, Letizia Mazzini, Sonia Messina, Maria Rosaria Monsurrò, Gabriele Mora, Nilo Riva, Romana Rizzi, Gabriele Siciliano, Vincenzo Silani, Isabella Simone, Gianni Sorarù, Paolo Volanti, Giuseppe Lauria
INTRODUCTION: Recent studies suggest that endoplasmic reticulum stress may play a critical role in the pathogenesis of amyotrophic lateral sclerosis (ALS) through an altered regulation of the proteostasis, the cellular pathway-balancing protein synthesis and degradation. A key mechanism is thought to be the dephosphorylation of eIF2α, a factor involved in the initiation of protein translation. Guanabenz is an alpha-2-adrenergic receptor agonist safely used in past to treat mild hypertension and is now an orphan drug...
August 11, 2017: BMJ Open
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