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https://www.readbyqxmd.com/read/29672831/acute-effects-of-riluzole-and-retigabine-on-axonal-excitability-in-patients-with-als-a-randomized-double-blind-placebo-controlled-cross-over-trial
#1
Maria O Kovalchuk, Jules Aac Heuberger, Boudewijn Thm Sleutjes, Dimitrios Ziagkos, Leonard H van de Berg, Toby A Ferguson, Hessel Franssen, Geert Jan Groeneveld
Increased excitability of motor neurons in patients with amyotrophic lateral sclerosis may be a relevant factor leading to motor neuron damage. This randomized, double-blind, 3-way cross-over, placebo-controlled study evaluated peripheral motor nerve excitability-testing as biomarker of hyperexcitability and assessed effects of riluzole and retigabine in 18 patients with amyotrophic lateral sclerosis. We performed excitability-testing at baseline, and twice after participants had received a single dose of either 100mg riluzole, 300mg retigabine or placebo...
April 19, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29644582/a-randomized-placebo-controlled-cross-over-pilot-study-of-riluzole-for-drug-refractory-irritability-in-autism-spectrum-disorder
#2
Logan K Wink, Ryan Adams, Paul S Horn, Charles R Tessier, Andrew P Bantel, Michael Hong, Rebecca C Shaffer, Ernest V Pedapati, Craig A Erickson
Riluzole is a glutamatergic modulator of particular interest in autism spectrum disorder (ASD). In this 12-week randomized, double-blind, placebo-controlled, crossover pilot study we evaluated the safety and tolerability of 5-week of adjunctive riluzole treatment (vs. 5-week of placebo, with 2-week washout period) targeting ASD-associated drug-refractory irritability in eight individuals age 12-25 years. All participants tolerated riluzole 200 mg per day, however there were no statistically significant findings for the overall treatment effect, the treatment effect by week within period of the study, or a cross-over effect across the periods of the study on the Clinical Global Impression Improvement Scale or the Aberrant Behavior Checklist Irritability subscale...
April 11, 2018: Journal of Autism and Developmental Disorders
https://www.readbyqxmd.com/read/29602909/age-dependent-sex-ratios-of-motor-neuron-disease-french-nationwide-study-and-meta-analysis
#3
Pasarlai Ahmadzai, Sofiane Kab, Tim Vlaar, Fanny Artaud, Laure Carcaillon-Bentata, Marianne Canonico, Frédéric Moisan, Alexis Elbaz
OBJECTIVE: To examine the relation of age with male-to-female (M/F) ratios and incidence rates of motor neuron disease (MND) in a French nationwide study and meta-analysis of incidence studies. METHODS: We used data from the French National Health Insurance databases. Patients with incident MND (2010-2014) were identified based on drug claims (riluzole), hospitalization records, death records, and long-term chronic disease benefits. We estimated age-specific M/F incidence ratios using Poisson regression...
March 30, 2018: Neurology
https://www.readbyqxmd.com/read/29596901/periaqueductal-gray-glutamatergic-cannabinoid-and-vanilloid-receptor-interplay-in-defensive-behavior-and-aversive-memory-formation
#4
Franklin P Back, Antonio P Carobrez
Stimulation of the midbrain periaqueductal gray matter (PAG) in humans elicits sensations of fear and impending terror, and mediates predator defensive responses in rodents. In rats, pharmacological stimulation of the dorsolateral portion of the PAG (dlPAG) with N-Methyl-d-Aspartate (NMDA) induces aversive conditioning that acts as an unconditioned stimulus (US). In the present work, we investigated the interplay between the vanilloid TRPV1 and cannabinoid CB1 receptors in the NMDA-dlPAG defensive response and in subsequent aversive learning...
March 26, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29576321/an-intracellular-allosteric-modulator-binding-pocket-in-sk2-ion-channels-is-shared-by-multiple-chemotypes
#5
Lily T-Y Cho, Aristos J Alexandrou, Rubben Torella, John Knafels, Jake Hobbs, Toni Taylor, Alex Loucif, Agnieszka Konopacka, Sigourney Bell, Edward B Stevens, Jay Pandit, Reto Horst, Jane M Withka, David C Pryde, Shenping Liu, Gareth T Young
Small conductance potassium (SK) ion channels define neuronal firing rates by conducting the after-hyperpolarization current. They are key targets in developing therapies where neuronal firing rates are dysfunctional, such as in epilepsy, Parkinson's, and amyotrophic lateral sclerosis (ALS). Here, we characterize a binding pocket situated at the intracellular interface of SK2 and calmodulin, which we show to be shared by multiple small-molecule chemotypes. Crystallization of this complex revealed that riluzole (approved for ALS) and an analog of the anti-ataxic agent (4-chloro-phenyl)-[2-(3,5-dimethyl-pyrazol-1-yl)-pyrimidin-4-yl]-amine (CyPPA) bind to and allosterically modulate via this site...
March 19, 2018: Structure
https://www.readbyqxmd.com/read/29572014/anticonvulsants-lamotrigine-and-riluzole-disrupt-maternal-behavior-in-postpartum-female-rats
#6
Meng Sun, Pan Huang, Yan Wang, Weihai Chen
Maternal behavior is a highly motivated and well-organized social behavior. Previous studies have reported that anticonvulsants are frequently used in postpartum bipolar disorder. However, the maternal disruptive effect of the anticonvulsants has not been explored. The purpose of the present study was to examine the effect of anticonvulsants lamotrigine and riluzole on maternal behavior in postpartum female rats. On postpartum Day 3, Sprague-Dawley mother rats were given a single intraperitoneal injection of vehicle, lamotrigine (15, 25, 35 mg/kg), or riluzole (2, 4, 8 mg/kg)...
March 20, 2018: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/29563879/trek-1-channel-expression-in-smooth-muscle-as-a-target-for-regulating-murine-intestinal-contractility-therapeutic-implications-for-motility-disorders
#7
Ruolin Ma, Mohsen Seifi, Maria Papanikolaou, James F Brown, Jerome D Swinny, Anthony Lewis
Gastrointestinal (GI) motility disorders such as irritable bowel syndrome (IBS) can occur when coordinated smooth muscle contractility is disrupted. Potassium (K+ ) channels regulate GI smooth muscle tone and are key to GI tract relaxation, but their molecular and functional phenotypes are poorly described. Here we define the expression and functional roles of mechano-gated K2P channels in mouse ileum and colon. Expression and distribution of the K2P channel family were investigated using quantitative RT-PCR (qPCR), immunohistochemistry and confocal microscopy...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29545836/gemals-a-promising-therapy-for-amyotrophic-lateral-sclerosis
#8
Michel Geffard, Arturo Mangas, Denis Bedat, Rafael Coveñas
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that currently has no cure. At present, the only approved treatment for ALS is Riluzole, a glutamate release blocker that improves life expectancy by 3-6 months. ALS-Endotherapia (GEMALS) is a novel therapeutic approach to treat ALS and the aim of the present study was to investigate the potential beneficial effects of this novel treatment. A total of 31 patients with ALS were assessed in the current study. Deceleration of the disease was observed in 83...
April 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29530700/effect-of-riluzole-on-spinal-cord-regeneration-with-hemisection-method-prior-to-injury
#9
Yusuf Sukru Caglar, Altan Demirel, Ihsan Dogan, Ramis Huseynov, Umit Eroglu, Onur Ozgüral, Cevriye Cansız, Burak Bahadir, Mustafa Cemil Kilinc, Eyyub S M Al-Beyati
OBJECTIVE: The pathophysiology of spinal cord injury (SCI) with the information obtained to date has not been fully elucidated. A safe drug or treatment protocol that results in cell regeneration for SCI remains unknown. Neuroprotective and neuroregenerative effects of Riluzole, administered after a SCI, have been shown in experimental studies. This study aimed to investigate the effect of Riluzole on neural regeneration in a rat SCI model. METHODS: Thirty-two rats were divided into eight groups, with four rats in each group...
March 9, 2018: World Neurosurgery
https://www.readbyqxmd.com/read/29525493/riluzole-disease-stage-and-survival-in-als
#10
Thanuja Dharmadasa, Matthew C Kiernan
No abstract text is available yet for this article.
March 7, 2018: Lancet Neurology
https://www.readbyqxmd.com/read/29525492/stage-at-which-riluzole-treatment-prolongs-survival-in-patients-with-amyotrophic-lateral-sclerosis-a-retrospective-analysis-of-data-from-a-dose-ranging-study
#11
Ton Fang, Ahmad Al Khleifat, Jacques-Henri Meurgey, Ashley Jones, P Nigel Leigh, Gilbert Bensimon, Ammar Al-Chalabi
BACKGROUND: Riluzole is the only drug to prolong survival for amyotrophic lateral sclerosis (ALS) and, at a dose of 100 mg, was associated with a 35% reduction in mortality in a clinical trial. A key question is whether the survival benefit occurs at an early stage of disease, late stage, or is spread throughout the course of the disease. To address this question, we used the King's clinical staging system to do a retrospective analysis of data from the original dose-ranging clinical trial of riluzole...
March 7, 2018: Lancet Neurology
https://www.readbyqxmd.com/read/29493465/riluzole-inhibits-proliferation-migration-and-cell-cycle-progression-and-induces-apoptosis-in-tumor-cells-of-various-origins
#12
Marta Kinga Lemieszek, Andrzej Stepulak, Katarzyna Sawa-Wejksza, Arkadiusz Czerwonka, Chrysanthy Ikonomidou, Wojciech Rzeski
Regardless of contemporary improvements in cancer treatment, the results of drug treatment are not always efficacious. Thus, the development of novel approaches that affect cancer cell-specific metabolic pathways are needed. Since much evidence has shown that tumor cell proliferation and motility are stimulated by glutamate via activation of its receptors, use of antagonists to these receptors may be the key to control cancer cell progression. Riluzole noncompetitive metabotropic glutamate receptor 1 (mGluR1) antagonist, commonly used to treat patients with amyotrophic lateral sclerosis (ALS), has shown some antineoplastic properties against melanoma, breast and prostate cancer...
February 28, 2018: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/29470458/prevalence-of-amyotrophic-lateral-sclerosis-united-states-2014
#13
Paul Mehta, Wendy Kaye, Jaime Raymond, Ruoming Wu, Theodore Larson, Reshma Punjani, Daniel Heller, Jessica Cohen, Tracy Peters, Oleg Muravov, Kevin Horton
Amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig's disease, is a progressive and fatal neuromuscular disease; the majority of ALS patients die within 2-5 years of receiving a diagnosis (1). Familial ALS, a hereditary form of the disease, accounts for 5%-10% of cases, whereas the remaining sporadic cases have no clearly defined etiology (1). ALS affects persons of all races and ethnicities; however, whites, males, non-Hispanics, persons aged >60 years, and those with a family history of ALS are more likely to develop the disease (1-3)...
February 23, 2018: MMWR. Morbidity and Mortality Weekly Report
https://www.readbyqxmd.com/read/29459142/modulation-of-human-corticospinal-excitability-by-paired-associative-stimulation-in-patients-with-amyotrophic-lateral-sclerosis-and-effects-of-riluzole
#14
M Ceccanti, E Onesti, A Rubino, C Cambieri, G Tartaglia, A Miscioscia, V Frasca, M Inghilleri
BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that causes an impairment in both the upper and lower motor neurons. The recent description of numerous non-motor signs points to an involvement of the neocortex networks that is more complex than was previously believed. Paired associative stimulation (PAS), a combination of transcranial magnetic stimulation (TMS) and peripheral nerve stimulation, can enhance motor output in the contralateral hand through an NMDA-mediated sensorimotor mechanism...
February 7, 2018: Brain Stimulation
https://www.readbyqxmd.com/read/29453787/a-phase-ii-trial-of-riluzole-an-antagonist-of-metabotropic-glutamate-receptor-1-grm1-signaling-in-patients-with-advanced-melanoma
#15
Janice M Mehnert, Ann W Silk, Yu Wen, J H Lee, Liesel Dudek, Byeong-Seon Jeong, Jiadong Li, Jason M Schenkel, Evita Sadimin, Michael Kane, Hongxia Lin, Weichung J Shih, Andrew Zloza, Suzie Chen, James S Goydos
Studies demonstrate that GRM, expressed by >60% of human melanomas, may be a therapeutic target. We performed a phase II trial of 100 mg po bid of riluzole, an inhibitor of GRM1 signaling, in patients with advanced melanoma with the primary endpoint of response rate. Thirteen patients with GRM1-positive tumors were enrolled. No objective responses were observed and accrual was stopped. Stable disease was noted in 6 (46%) patients, with 1 patient on study for 42 weeks. Riluzole was well-tolerated, with fatigue (62%) as the most common adverse event...
February 17, 2018: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/29440566/comprehensive-systematic-review-summary-treatment-of-cerebellar-motor-dysfunction-and-ataxia-report-of-the-guideline-development-dissemination-and-implementation-subcommittee-of-the-american-academy-of-neurology
#16
Theresa A Zesiewicz, George Wilmot, Sheng-Han Kuo, Susan Perlman, Patricia E Greenstein, Sarah H Ying, Tetsuo Ashizawa, S H Subramony, Jeremy D Schmahmann, K P Figueroa, Hidehiro Mizusawa, Ludger Schöls, Jessica D Shaw, Richard M Dubinsky, Melissa J Armstrong, Gary S Gronseth, Kelly L Sullivan
OBJECTIVE: To systematically review evidence regarding ataxia treatment. METHODS: A comprehensive systematic review was performed according to American Academy of Neurology methodology. CONCLUSIONS: For patients with episodic ataxia type 2, 4-aminopyridine 15 mg/d probably reduces ataxia attack frequency over 3 months (1 Class I study). For patients with ataxia of mixed etiology, riluzole probably improves ataxia signs at 8 weeks (1 Class I study)...
March 6, 2018: Neurology
https://www.readbyqxmd.com/read/29405033/therapy-in-amyotrophic-lateral-sclerosis-als-an-unexpected-evolving-scenario
#17
Vincenzo Silani
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease resulting in increasing disability, being uniformly fatal. Since its approval in the 1990s, riluzole remained for long time the unique treatment, offering modest survival benefit. Most recently a second drug has been approved by the US Food and Drug Administration for treatment of ALS: edaravone. Significant advances have been made in the symptomatic management of the disease but more effective drug therapy targeting disease progression is still dreadfully needed, the success appearing almost a miracle...
December 1, 2017: Archives Italiennes de Biologie
https://www.readbyqxmd.com/read/29404735/riluzole-and-other-prognostic-factors-in-als-a-population-based-registry-study-in-italy
#18
Jessica Mandrioli, Sara Angela Malerba, Ettore Beghi, Nicola Fini, Antonio Fasano, Elisabetta Zucchi, Silvia De Pasqua, Carlo Guidi, Emilio Terlizzi, Elisabetta Sette, Alessandro Ravasio, Mario Casmiro, Fabrizio Salvi, Rocco Liguori, Lucia Zinno, Yasmin Handouk, Romana Rizzi, Annamaria Borghi, Rita Rinaldi, Doriana Medici, Mario Santangelo, Enrico Granieri, Vittoria Mussuto, Marina Aiello, Salvatore Ferro, Marco Vinceti
OBJECTIVE: In this prospective population-based registry study on ALS survival, we investigated the role of riluzole treatment, together with other clinical factors, on the prognosis in incident ALS cases in Emilia Romagna Region (ERR), Italy. METHODS: A registry for ALS has been collecting all incident cases in ERR since 2009. Detailed clinical data from all patients diagnosed with ALS between 1.1.2009 and 31.12.2014 have been analyzed for this study, with last follow up date set at 31...
April 2018: Journal of Neurology
https://www.readbyqxmd.com/read/29399045/disease-modifying-and-symptomatic-treatment-of-amyotrophic-lateral-sclerosis
#19
REVIEW
Johannes Dorst, Albert C Ludolph, Annemarie Huebers
In this review, we summarize the most important recent developments in the treatment of amyotrophic lateral sclerosis (ALS). In terms of disease-modifying treatment options, several drugs such as dexpramipexole, pioglitazone, lithium, and many others have been tested in large multicenter trials, albeit with disappointing results. Therefore, riluzole remains the only directly disease-modifying drug. In addition, we discuss antisense oligonucleotides (ASOs) as a new and potentially causal treatment option. Progress in symptomatic treatments has been more important...
2018: Therapeutic Advances in Neurological Disorders
https://www.readbyqxmd.com/read/29396541/tdp-43-self-interaction-is-modulated-by-redox-active-compounds-auranofin-chelerythrine-and-riluzole
#20
Moritz Oberstadt, Jens Stieler, David Larbi Simpong, Ute Römuß, Nicole Urban, Michael Schaefer, Thomas Arendt, Max Holzer
Amyotrophic lateral sclerosis (ALS) represents a fatal neurodegenerative disease, which is characterized by a rapid loss of lower and upper motor neurons. As a major neuropathological hallmark, protein aggregates containing the Transactivating Response Region (TAR) DNA Binding Protein (TDP-43) are detectable in about 95% of sporadic ALS patients. TDP-43 interacts with itself physiologically to form liquid droplets, which may progress to pathological aggregates. In this study, we established the NanoBit luciferase complementation assay to measure TDP-43 self-interaction and found the fusion of the split luciferase subunits to the N-terminus of the protein as the strongest interacting partners...
February 2, 2018: Scientific Reports
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