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Ibudilast

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https://www.readbyqxmd.com/read/27826212/a-double-blind-randomized-placebo-controlled-pilot-trial-to-determine-the-efficacy-and-safety-of-ibudilast-a-potential-glial-attenuator-in-chronic-migraine
#1
Yuen H Kwok, James E Swift, Parisa Gazerani, Paul Rolan
BACKGROUND: Chronic migraine (CM) is problematic, and there are few effective treatments. Recently, it has been hypothesized that glial activation may be a contributor to migraine; therefore, this study investigated whether the potential glial inhibitor, ibudilast, could attenuate CM. METHODS: The study was of double-blind, randomized, placebo-controlled, two-period crossover design. Participants were randomized to receive either ibudilast (40 mg twice daily) or placebo treatment for 8 weeks...
2016: Journal of Pain Research
https://www.readbyqxmd.com/read/27521810/design-rationale-and-baseline-characteristics-of-the-randomized-double-blind-phase-ii-clinical-trial-of-ibudilast-in-progressive-multiple-sclerosis
#2
Robert J Fox, Christopher S Coffey, Merit E Cudkowicz, Trevis Gleason, Andrew Goodman, Eric C Klawiter, Kazuko Matsuda, Michelle McGovern, Robin Conwit, Robert Naismith, Akshata Ashokkumar, Robert Bermel, Dixie Ecklund, Maxine Koepp, Jeffrey Long, Sneha Natarajan, Srividya Ramachandran, Thomai Skaramagas, Brenda Thornell, Jon Yankey, Mark Agius, Khurram Bashir, Bruce Cohen, Patricia Coyle, Silvia Delgado, Dana Dewitt, Angela Flores, Barbara Giesser, Myla Goldman, Burk Jubelt, Neil Lava, Sharon Lynch, Augusto Miravalle, Harold Moses, Daniel Ontaneda, Jai Perumal, Michael Racke, Pavle Repovic, Claire Riley, Christopher Severson, Shlomo Shinnar, Valerie Suski, Bianca Weinstock-Gutman, Vijayshree Yadav, Aram Zabeti
BACKGROUND: Primary and secondary progressive multiple sclerosis (MS), collectively called progressive multiple sclerosis (PMS), is characterized by gradual progression of disability. The current anti-inflammatory treatments for MS have little or no efficacy in PMS in the absence of obvious active inflammation. Optimal biomarkers for phase II PMS trials is unknown. Ibudilast is an inhibitor of macrophage migration inhibitor factor and phosphodiesterases-4 and -10 and exhibits possible neuroprotective properties...
September 2016: Contemporary Clinical Trials
https://www.readbyqxmd.com/read/27501293/ibudilast-for-the-treatment-of-multiple-sclerosis
#3
Andrew D Goodman, Tirisham Gyang, Andrew D Smith
INTRODUCTION: Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system (CNS) characterized by inflammatory demyelination and progressive axonal loss. Clinically, this is manifest as relapsing and remitting neurological symptoms and progressive accumulation of disability. Ibudilast is a nonselective phosphodiesterase inhibitor which works by blocking the cleavage of cyclic adenosine monophosphate (cAMP). It has been found to have anti-inflammatory and neuroprotective properties in animal studies and in-vitro studies; it is currently being studied in progressive MS...
October 2016: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/27343385/ibudilast-attenuates-expression-of-behavioral-sensitization-to-cocaine-in-male-and-female-rats
#4
Ryan S Poland, Yun K Hahn, Pamela E Knapp, Patrick M Beardsley, M Scott Bowers
There are no FDA-approved pharmacotherapies for cocaine use disorder, indicating a need to identify novel reagents with therapeutic potential. Ibudilast is an anti-inflammatory glial attenuator and non-selective phosphodiesterase inhibitor currently undergoing clinical evaluations for methamphetamine, opiate, and alcohol abuse disorders. We previously showed that twice daily (b.i.d.) ibudilast reduces the development of methamphetamine sensitization in male mice. However, nothing is known about the ability of ibudilast to modulate the expression of sensitization that occurs after drug re-exposure during abstinence, effects on cocaine-mediated behaviors, or potentially sexually dimorphic effects...
October 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27269956/safety-of-intravenous-methamphetamine-administration-during-ibudilast-treatment
#5
Dustin Z DeYoung, Keith G Heinzerling, Aimee-Noelle Swanson, John Tsuang, Benjamin A Furst, Yi Yi, Ying Nian Wu, David E Moody, David M Andrenyak, Steven J Shoptaw
BACKGROUND: Methamphetamine dependence is a significant public health concern without any approved medications for treatment. We evaluated ibudilast, a nonselective phosphodiesterase inhibitor, to assess the safety and tolerability during intravenous methamphetamine administration. We conducted a randomized, double-blind, placebo-controlled, within-subjects crossover clinical trial. METHODS: Participants received ibudilast (20 mg twice daily followed by 50 mg twice daily) and placebo, with order determined by randomization, and then underwent intravenous methamphetamine challenges (15 and 30 mg)...
August 2016: Journal of Clinical Psychopharmacology
https://www.readbyqxmd.com/read/27163643/the-glial-cell-modulator-ibudilast-attenuates-neuroinflammation-and-enhances-retinal-ganglion-cell-viability-in-glaucoma-through-protein-kinase-a-signaling
#6
Jorge L Cueva Vargas, Nicolas Belforte, Adriana Di Polo
Glaucoma is a neurodegenerative disease and the leading cause of irreversible blindness worldwide. Vision deficits in glaucoma result from the selective loss of retinal ganglion cells (RGC). Glial cell-mediated neuroinflammation has been proposed to contribute to disease pathophysiology, but whether this response is harmful or beneficial for RGC survival is not well understood. To test this, we characterized the role of ibudilast, a clinically approved cAMP phosphodiesterase (PDE) inhibitor with preferential affinity for PDE type 4 (PDE4)...
September 2016: Neurobiology of Disease
https://www.readbyqxmd.com/read/26993372/ibudilast-attenuates-subjective-effects-of-methamphetamine-in-a-placebo-controlled-inpatient-study
#7
Matthew J Worley, Keith G Heinzerling, Daniel J O Roche, Steve Shoptaw
BACKGROUND: Despite numerous clinical trials no efficacious medications for methamphetamine (MA) have been identified. Neuroinflammation, which has a role in MA-related reward and neurodegeneration, is a novel MA pharmacotherapy target. Ibudilast inhibits activation of microglia and pro-inflammatory cytokines and has reduced MA self-administration in preclinical research. This study examined whether ibudilast would reduce subjective effects of MA in humans. METHODS: Adult, non-treatment seeking, MA-dependent volunteers (N=11) received oral placebo, moderate ibudilast (40 mg), and high-dose ibudilast (100mg) via twice-daily dosing for 7 days each in an inpatient setting...
May 1, 2016: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/26859874/the-effects-of-the-toll-like-receptor-4-antagonist-ibudilast-on-sevoflurane-s-minimum-alveolar-concentration-and-the-delayed-remifentanil-induced-increase-in-the-minimum-alveolar-concentration-in-rats
#8
Daniel Ruiz-Pérez, Javier Benito, Gonzalo Polo, Carlota Largo, Delia Aguado, Luis Sanz, Ignacio A Gómez de Segura
BACKGROUND: Ultralow doses of naloxone, an opioid and toll-like receptor 4 antagonist, blocked remifentanil-induced hyperalgesia and the associated increase in the minimum alveolar concentration (MAC), but not tolerance. The aim was to determine the effects of the toll-like receptor 4 antagonist, ibudilast, on the MAC in the rat and how it might prevent the effects of remifentanil. METHODS: Male Wistar rats were randomly allocated to 5 treatment groups (n = 7 per group): 10 mg/kg ibudilast intraperitoneally, 240 µg/kg/h remifentanil IV, ibudilast plus remifentanil, remifentanil plus naloxone IV, or saline...
May 2016: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/26367865/glial-attenuation-with-ibudilast-in-the-treatment-of-medication-overuse-headache-a-double-blind-randomized-placebo-controlled-pilot-trial-of-efficacy-and-safety
#9
Jacinta L Johnson, Yuen H Kwok, Nicole M Sumracki, James E Swift, Mark R Hutchinson, Kirk Johnson, Desmond B Williams, Jonathon Tuke, Paul E Rolan
BACKGROUND: Medication overuse headache (MOH) is a condition bordering between a chronic pain condition and a substance dependence disorder. Activation of immunocompetent glial cells in the central nervous system has been linked to both pathological pain and drug addiction/reward. Preclinically, ibudilast attenuates glial activation and is able to reduce neuropathic pain and markers of substance dependence. We therefore hypothesized ibudilast would reduce headache burden and opioid analgesic requirements in patients with opioid overuse headache...
October 2015: Headache
https://www.readbyqxmd.com/read/26218293/impaired-synaptic-development-in-a-maternal-immune-activation-mouse-model-of-neurodevelopmental-disorders
#10
Pierluca Coiro, Ragunathan Padmashri, Anand Suresh, Elizabeth Spartz, Gurudutt Pendyala, Shinnyi Chou, Yoosun Jung, Brittney Meays, Shreya Roy, Nagsen Gautam, Yazen Alnouti, Ming Li, Anna Dunaevsky
Both genetic and environmental factors are thought to contribute to neurodevelopmental and neuropsychiatric disorders with maternal immune activation (MIA) being a risk factor for both autism spectrum disorders and schizophrenia. Although MIA mouse offspring exhibit behavioral impairments, the synaptic alterations in vivo that mediate these behaviors are not known. Here we employed in vivo multiphoton imaging to determine that in the cortex of young MIA offspring there is a reduction in number and turnover rates of dendritic spines, sites of majority of excitatory synaptic inputs...
November 2015: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/26017524/emerging-treatments-for-the-primary-headache-disorders
#11
REVIEW
Nathaniel M Schuster, Sarah Vollbracht, Alan M Rapoport
Migraine and cluster headache are common, episodic, often chronic and disabling disorders of the brain. Although there are many standard treatment techniques, none are ideal. This article reviews various novel pharmacologic and device-related treatments for migraine and cluster headache. Emphasis is given to recent advances in the development of monoclonal antibodies (mAbs) targeting calcitonin gene-related peptide (CGRP) and its receptor, including promising results from phase 2 trials studying the safety and efficacy of LY2951742, ALD403 and TEV-48125, three anti-CGRP mAbs...
May 2015: Neurological Sciences
https://www.readbyqxmd.com/read/26005122/-american-academy-of-neurology-washington-18-25%C3%A2-april%C3%A2-2015
#12
I Sibon, B de Toffol, J-P Azulay, F Sellal, C Thomas-Antérion, J-M Léger, C Pierrot-Deseilligny
CEREBROVASCULAR DISEASES: The benefit of the thrombectomy using stents retrievers in the acute stroke phase is now demonstrated when there is a proximal occlusion of an intracranial artery, whatever its mechanism. The place of the anticoagulants in the management of cervical artery dissections remains uncertain, while the benefit of the blood pressure control in the secondary prevention of deep and lobar intracerebral hemorrhages is critical. The development of cardiac MRI, prolonged cardiac monitoring and transcranial doppler seems to improve the diagnosis of cardio-embolic sources of stroke...
June 2015: Revue Neurologique
https://www.readbyqxmd.com/read/25975386/the-effects-of-ibudilast-a-glial-activation-inhibitor-on-opioid-withdrawal-symptoms-in-opioid-dependent-volunteers
#13
Ziva D Cooper, Kirk W Johnson, Martina Pavlicova, Andrew Glass, Suzanne K Vosburg, Maria A Sullivan, Jeanne M Manubay, Diana M Martinez, Jermaine D Jones, Phillip A Saccone, Sandra D Comer
Glial activation is hypothesized to contribute directly to opioid withdrawal. This study investigated the dose-dependent effects of a glial cell modulator, ibudilast, on withdrawal symptoms in opioid-dependent volunteers after abrupt discontinuation of morphine administration. Non-treatment-seeking heroin-dependent volunteers (n = 31) completed the in-patient, double-blind, placebo-controlled, within-subject and between-group study. Volunteers were maintained on morphine (30 mg, QID) for 14 days and placebo (0 mg, QID) for the last 7 days of the 3-week study...
July 2016: Addiction Biology
https://www.readbyqxmd.com/read/25962787/ibudilast-reverses-the-decrease-in-the-synaptic-signaling-protein-phosphatidylethanolamine-binding-protein-1-pebp1-produced-by-chronic-methamphetamine-intake-in-rats
#14
Sergios Charntikov, Steven T Pittenger, Ishwor Thapa, Dhundy R Bastola, Rick A Bevins, Gurudutt Pendyala
BACKGROUND: Chronic methamphetamine intake has been shown to induce a neuroinflammatory state leading to significant changes in brain functioning including behavioral changes. These changes can persist for years after drug use is discontinued and likely contribute to the risk of relapse. A better understanding of inflammation responses associated with methamphetamine intake may help in designing novel and more efficacious treatment strategies. METHODS: Rats were trained to self-administer methamphetamine or saline on a variable ratio 3 schedule of reinforcement (25 days)...
July 1, 2015: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/25887766/progressive-multiple-sclerosis
#15
REVIEW
Daniel Ontaneda, Robert J Fox
PURPOSE OF REVIEW: The purpose of this study is to highlight the pathological features and clinical aspects of progressive multiple sclerosis (PMS) and also the results of clinical trial experience to date and review ongoing clinical trials and prospective new treatment options. This study will explain the challenges of clinical trial design in PMS. RECENT FINDINGS: Multiple sclerosis (MS) has been identified as a chronic immune mediated disease, and the progressive phase of the disease appears to have significant neurodegenerative mechanisms...
June 2015: Current Opinion in Neurology
https://www.readbyqxmd.com/read/25856304/drug-repurposing-a-systematic-approach-to-evaluate-candidate-oral-neuroprotective-interventions-for-secondary-progressive-multiple-sclerosis
#16
Hanna M Vesterinen, Peter Connick, Cadi M J Irvine, Emily S Sena, Kieren J Egan, Gary G Carmichael, Afiyah Tariq, Sue Pavitt, Jeremy Chataway, Malcolm R Macleod, Siddharthan Chandran
OBJECTIVE: To develop and implement an evidence based framework to select, from drugs already licenced, candidate oral neuroprotective drugs to be tested in secondary progressive multiple sclerosis. DESIGN: Systematic review of clinical studies of oral putative neuroprotective therapies in MS and four other neurodegenerative diseases with shared pathological features, followed by systematic review and meta-analyses of the in vivo experimental data for those interventions...
2015: PloS One
https://www.readbyqxmd.com/read/25386959/codeine-induced-hyperalgesia-and-allodynia-investigating-the-role-of-glial-activation
#17
COMPARATIVE STUDY
J L Johnson, P E Rolan, M E Johnson, L Bobrovskaya, D B Williams, K Johnson, J Tuke, M R Hutchinson
Chronic morphine therapy has been associated with paradoxically increased pain. Codeine is a widely used opioid, which is metabolized to morphine to elicit analgesia. Prolonged morphine exposure exacerbates pain by activating the innate immune toll-like receptor-4 (TLR4) in the central nervous system. In silico docking simulations indicate codeine also docks to MD2, an accessory protein for TLR4, suggesting potential to induce TLR4-dependent pain facilitation. We hypothesized codeine would cause TLR4-dependent hyperalgesia/allodynia that is disparate from its opioid receptor-dependent analgesic rank potency...
2014: Translational Psychiatry
https://www.readbyqxmd.com/read/25175870/opportunities-for-the-development-of-neuroimmune-therapies-in-addiction
#18
REVIEW
Lara A Ray, Daniel J O Roche, Keith Heinzerling, Steve Shoptaw
Studies have implicated neuroinflammatory processes in the pathophysiology of various psychiatric conditions, including addictive disorders. Neuroimmune signaling represents an important and relatively poorly understood biological process in drug addiction. The objective of this review is to update the field on recent developments in neuroimmune therapies for addiction. First, we review studies of neuroinflammation in relation to alcohol and methamphetamine dependence followed by a section on neuroinflammation and accompanying neurocognitive dysfunction in HIV infection and concomitant substance abuse...
2014: International Review of Neurobiology
https://www.readbyqxmd.com/read/25038445/pretreatment-with-antiasthmatic-drug-ibudilast-ameliorates-a%C3%AE-1-42-induced-memory-impairment-and-neurotoxicity-in-mice
#19
Hao Wang, Zhen lin Mei, Kai Long Zhong, Mei Hu, Yan Long, Ming Xing Miao, Ning Li, Tian Hua Yan, Hao Hong
Amyloid-β peptide (Aβ) is thought to be associated with the progressive neuronal death observed in Alzheimer's disease (AD). However, effective neuroprotective approaches against Aβ neurotoxicity are unavailable. Here, we investigated possible preventive effects of ibudilast, as a pharmacologic phosphodiesterase inhibitor, currently used for treatment of inflammatory diseases such as asthma, on Aβ 1-42-induced neuroinflammatory, apoptotic responses and memory impairment. We found that pretreatment with ibudilast (4 or 12 mg/kg, i...
September 2014: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/25017887/neuroinflammatory-contributions-to-pain-after-sci-roles-for-central-glial-mechanisms-and-nociceptor-mediated-host-defense
#20
REVIEW
Edgar T Walters
Neuropathic pain after spinal cord injury (SCI) is common, often intractable, and can be severely debilitating. A number of mechanisms have been proposed for this pain, which are discussed briefly, along with methods for revealing SCI pain in animal models, such as the recently applied conditioned place preference test. During the last decade, studies of animal models have shown that both central neuroinflammation and behavioral hypersensitivity (indirect reflex measures of pain) persist chronically after SCI...
August 2014: Experimental Neurology
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