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Parkinson drugs trials

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https://www.readbyqxmd.com/read/29764353/non-motor-parkinson-disease-new-concepts-and-personalised-management
#1
Nataliya Titova, K Ray Chaudhuri
Most patients with Parkinson disease (PD) have non-motor symptoms (NMS), and on average these can range from four to 19 different symptoms. NMS dominate the prodromal phase of PD and some may serve as clinical biomarkers of PD. NMS can be dopaminergic, non-dopaminergic, of genetic origin or drug induced. Clinical assessment of NMS should include the NMS Questionnaire (completed by patients) for screening, as recommended by the International Parkinson and Movement Disorders Society and other international societies...
May 21, 2018: Medical Journal of Australia
https://www.readbyqxmd.com/read/29759929/entacapone-and-prostate-cancer-in-parkinson-s-disease-patients-a-large-veterans-affairs-healthcare-system-study
#2
Jacqueline M Major, Diane Dong, Francesca Cunningham, Kunthel By, Kwan Hur, David C Shih, Rong Jiang, Gerald D Podskalny, XiangMing Wei, Simone Pinheiro, Steven T Bird, Stephine Keeton, David J Graham
BACKGROUND: An increased incidence of prostate cancer was observed in Parkinson's disease (PD) patients treated with entacapone during a pre-approval randomized clinical trial; the relation has not been robustly investigated in the U.S. ambulatory setting. OBJECTIVE: To investigate whether entacapone is associated with prostate cancer and to assess whether the associations are correlated with advanced disease at the time of cancer diagnosis. METHODS: Using data from the Department of Veterans Affairs healthcare system, new-user cohorts were created of PD patients treated with add-on entacapone or add-on dopamine agonist/monoamine oxidase B inhibitors between January 2000 and December 2014...
May 5, 2018: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/29758999/movement-disorders-associated-with-antipsychotic-medication-in-people-with-schizophrenia-an-overview-of-cochrane-reviews-and-meta-analysis
#3
Davide Martino, Vikram Karnik, Sydney Osland, Thomas R E Barnes, Tamara M Pringsheim
Movement disorders associated with antipsychotic medications are relatively common, stigmatising, and potentially disabling. Their prevalence in people with psychosis who are prescribed second-generation antipsychotics (SGAs) is uncertain, as is their level of recognition by clinicinas. We conducted meta-analyses of randomised controlled trials included in the Cochrane Database of Systematic Reviews on schizophrenia and schizophrenia-like psychoses to estimate the prevalence of new-onset dystonia, akathisia, parkinsonism, and tremor with SGAs (amisulpride, asenapine, aripiprazole, clozapine, olanzapine, paliperidone, quetiapine, risperidone, L-sulpiride, and ziprasidone) approved in Canada and the UK, comparing them with haloperidol and chlorpromazine...
January 1, 2018: Canadian Journal of Psychiatry. Revue Canadienne de Psychiatrie
https://www.readbyqxmd.com/read/29756335/treatment-of-restless-legs-syndrome-evidence-based-review-and-implications-for-clinical-practice-revised-2017-%C3%A2
#4
REVIEW
Juliane Winkelmann, Richard P Allen, Birgit Högl, Yuichi Inoue, Wolfgang Oertel, Aaro V Salminen, John W Winkelman, Claudia Trenkwalder, Cristina Sampaio
The objective of the current review was to update the previous evidence-based medicine review of treatments for restless legs syndrome published in 2008. All randomized, controlled trials (level I) with a high quality score published between January 2007 and January 2017 were reviewed. Forty new studies qualified for efficacy review. Pregabalin, gabapentin enacarbil, and oxycodone/naloxone, which did not appear in the previous review, have accrued data to be considered efficacious. Likewise, new data enable the modification of the level of efficacy for rotigotine from likely efficacious to efficacious...
May 14, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/29752185/brain-penetrant-kinase-inhibitors-learning-from-kinase-neuroscience-discovery
#5
REVIEW
Yuan Shi, Mary Mader
A recent review of kinase inhibitors in clinical trials for brain cancer noted differences in the properties of these compounds relative to the mean property parameters associated with drugs marketed for CNS-associated conditions. However, many of these kinase drugs arose from opportunistic observations of brain activity, rather than design or flow schemes focused on optimizing CNS penetration. Thus, this digest examines kinase inhibitors that have been developed specifically for neurodegenerative indications such as Alzheimer's or Parkinson's disease, and considers design, flow scheme, and the physicochemical properties associated with compounds that have demonstrated brain penetrance...
May 4, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29734182/a-systematic-review-and-meta-analysis-of-the-effectiveness-of-acetylcholinesterase-inhibitors-and-memantine-in-treating-the-cognitive-symptoms-of-dementia
#6
Ruth Knight, Mizanur Khondoker, Nicholas Magill, Robert Stewart, Sabine Landau
BACKGROUND: Acetylcholinesterase inhibitors (AChEIs) and memantine are commonly used in the management of dementia. In routine clinical practice, dementia is often monitored via the Mini-Mental State Examination (MMSE). We conducted a systematic review and meta-analysis of the effects of these drugs on MMSE scores. SUMMARY: Eighty trials were identified. Pooled effect estimates were in favour of both AChEIs and memantine at 6 months. Meta-regression indicated that dementia subtype was a moderator of AChEI treatment effect, with the effect of treatment versus control twice as high for patients with Parkinson disease dementia/ dementia with Lewy bodies (2...
May 7, 2018: Dementia and Geriatric Cognitive Disorders
https://www.readbyqxmd.com/read/29727504/noninvasive-pk11195-pet-image-analysis-techniques-can-detect-abnormal-cerebral-microglial-activation-in-parkinson-s-disease
#7
Yeona Kang, P David Mozley, Ajay Verma, David Schlyer, Claire Henchcliffe, Susan A Gauthier, Ping C Chiao, Bin He, Anastasia Nikolopoulou, Jean Logan, Jenna M Sullivan, Kane O Pryor, Jacob Hesterman, Paresh J Kothari, Shankar Vallabhajosula
BACKGROUND AND PURPOSE: Neuroinflammation has been implicated in the pathophysiology of Parkinson's disease (PD), which might be influenced by successful neuroprotective drugs. The uptake of [11 C](R)-PK11195 (PK) is often considered to be a proxy for neuroinflammation, and can be quantified using the Logan graphical method with an image-derived blood input function, or the Logan reference tissue model using automated reference region extraction. The purposes of this study were (1) to assess whether these noninvasive image analysis methods can discriminate between patients with PD and healthy volunteers (HVs), and (2) to establish the effect size that would be required to distinguish true drug-induced changes from system variance in longitudinal trials...
May 4, 2018: Journal of Neuroimaging: Official Journal of the American Society of Neuroimaging
https://www.readbyqxmd.com/read/29705555/da-9701-on-gastric-motility-in-patients-with-parkinson-s-disease-a-randomized-controlled-trial
#8
Cheol Min Shin, Yoon Jin Lee, Jong-Min Kim, Jee Young Lee, Kyung-Joon Kim, Yoon Jin Choi, Nayoung Kim, Dong Ho Lee
INTRODUCTION: To evaluate the effect of DA-9701, a novel prokinetic drug, on gastric motility evaluated by magnetic resonance imaging in patients with Parkinson's disease (PD). METHODS: Forty PD patients were randomly allocated to receive either domperidone or DA-9701. Their gastric functions were evaluated using magnetic resonance imaging before and after 4-week treatment period. Information on levodopa daily dose, disease duration, and Unified PD Rating Scale scores was collected...
April 21, 2018: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/29681869/deep-brain-stimulation-of-the-internal-globus-pallidus-improves-response-initiation-and-proactive-inhibition-in-patients-with-parkinson-s-disease
#9
Yixin Pan, Linbin Wang, Yingying Zhang, Chencheng Zhang, Xian Qiu, Yuyan Tan, Haiyan Zhou, Bomin Sun, Dianyou Li
Background: Impulse control disorder is not uncommon in patients with Parkinson's disease (PD) who are treated with dopamine replacement therapy and subthalamic deep brain stimulation (DBS). Internal globus pallidus (GPi)-DBS is increasingly used, but its role in inhibitory control has rarely been explored. In this study, we evaluated the effect of GPi-DBS on inhibitory control in PD patients. Methods: A stop-signal paradigm was used to test response initiation, proactive inhibition, and reactive inhibition...
2018: Frontiers in Psychology
https://www.readbyqxmd.com/read/29624723/randomized-clinical-trial-of-rt001-early-signals-of-efficacy-in-friedreich-s-ataxia
#10
Theresa Zesiewicz, Frederic Heerinckx, Robert De Jager, Omid Omidvar, Marcus Kilpatrick, Jessica Shaw, Mikhail S Shchepinov
BACKGROUND: RT001 is a deuterated ethyl linoleate that inhibits lipid peroxidation and is hypothesized to reduce cellular damage and recover mitochondrial function in degenerative diseases such as Friedreich's ataxia. OBJECTIVE: To evaluate the safety, pharmacokinetics, and preliminary efficacy of RT001 in Friedreich's ataxia patients. DESIGN/METHODS: We conducted a phase I/II double-blind, comparator-controlled trial with 2 doses of RT001 in Friedreich's ataxia patients (9 subjects each cohort)...
April 6, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/29605730/metabotropic-glutamate-receptors-targets-for-neuroprotective-therapies-in-parkinson-disease
#11
REVIEW
Gunasingh J Masilamoni, Yoland Smith
Metabotropic glutamate receptors (mGluRs) are heavily expressed throughout the basal ganglia (BG), where they modulate neuronal excitability, transmitter release and long term synaptic plasticity. Therefore, targeting specific mGluR subtypes by means of selective drugs could be a possible strategy for restoring normal synaptic function and neuronal activity of the BG in Parkinson disease (PD). Preclinical studies have revealed that specific mGluR subtypes mediate significant neuroprotective effects that reduce toxin-induced midbrain dopaminergic neuronal death in animal models of PD...
March 29, 2018: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29532440/pooled-analyses-of-phase-iii-studies-of-ads-5102-amantadine-extended-release-capsules-for-dyskinesia-in-parkinson-s-disease
#12
Lawrence W Elmer, Jorge L Juncos, Carlos Singer, Daniel D Truong, Susan R Criswell, Sotirios Parashos, Larissa Felt, Reed Johnson, Rajiv Patni
BACKGROUND: Although levodopa is considered the most effective pharmacotherapy for motor symptoms of Parkinson's disease (PD), chronic use is associated with motor complications, including fluctuating response and unpredictable, involuntary movements called dyskinesia. ADS-5102 (amantadine) extended-release (ER) capsules (GOCOVRITM ) is a recent US FDA-approved treatment for dyskinesia in PD patients. ADS-5102 is a high-dose, ER formulation of amantadine, administered orally once daily at bedtime, that achieves high plasma drug concentrations throughout the day...
April 2018: CNS Drugs
https://www.readbyqxmd.com/read/29521210/phosphodiesterase-10-inhibitors-novel-perspectives-for-psychiatric-and-neurodegenerative-drug-discovery
#13
Agnieszka Zagorska, Anna Partyka, Adam Bucki, Alicja Gawalska, Anna Czopek, Maciej Pawlowski
BACKGROUND: The phosphodiesterase 10 (PDE10) family, identified in 1999, is mainly expressed in the brain, particularly in the striatum, within the medium spiny neurons, nucleus accumbens, and olfactory tubercle. Inhibitors of PDE10 (PDE10-Is) are a conceptually rational subject for medicinal chemistry with potential use in the treatment of psychiatric and neurodegenerative diseases. OBJECTIVE: This review is based on peer-reviewed published articles, and summarizes the cellular and molecular biology of PDE10 as a rational target for psychiatric and neurodegenerative drug discovery...
March 8, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29508455/treatment-of-autonomic-dysfunction-in-parkinson-disease-and-other-synucleinopathies
#14
REVIEW
Jose-Alberto Palma, Horacio Kaufmann
Dysfunction of the autonomic nervous system afflicts most patients with Parkinson disease and other synucleinopathies such as dementia with Lewy bodies, multiple system atrophy, and pure autonomic failure, reducing quality of life and increasing mortality. For example, gastrointestinal dysfunction can lead to impaired drug pharmacodynamics causing a worsening in motor symptoms, and neurogenic orthostatic hypotension can cause syncope, falls, and fractures. When recognized, autonomic problems can be treated, sometimes successfully...
March 2018: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/29503332/expanding-indications-for-deep-brain-stimulation
#15
Paresh K Doshi
It has been three decades since the first application of deep brain stimulation (DBS) for tremors was described by Benabid. Over the years, the indications for the performance of DBS have been expanding. There are now more than 1,50,000 patients around the world who have undergone DBS for various disorders. The main appeal of DBS is in its reversibility and titratability. Though the initial interest in DBS was for pain, the main indications for DBS have been movement disorders. Despite its wide appeal and "perceived" advantage, United States Food and Drug Administration, the nodal agency for approving therapies, has been cautious and guarded in providing approvals...
March 2018: Neurology India
https://www.readbyqxmd.com/read/29502862/peroxisome-proliferator-activated-receptor-gamma-coactivator-1-alpha-as-a-novel-target-for-bipolar-disorder-and-other-neuropsychiatric-disorders
#16
REVIEW
Andrew A Nierenberg, Sharmin A Ghaznavi, Isadora Sande Mathias, Kristen K Ellard, Jessica A Janos, Louisa G Sylvia
Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha) is a protein that regulates metabolism and inflammation by activating nuclear receptors, especially the family of peroxisome proliferator-activated receptors (PPARs). PGC-1 alpha and PPARs also regulate mitochondrial biogenesis, cellular energy production, thermogenesis, and lipid metabolism. Brain energy metabolism may also be regulated in part by the interaction between PGC-1 alpha and PPARs. Because neurodegenerative diseases (Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis) and bipolar disorder have been associated with dysregulated mitochondrial and brain energy metabolism, PGC-1 alpha may represent a potential drug target for these conditions...
May 1, 2018: Biological Psychiatry
https://www.readbyqxmd.com/read/29497575/pimavanserin-a-novel-drug-approved-to-treat-parkinson-s-disease-psychosis
#17
REVIEW
Amanda K Kitten, Sarah A Hallowell, Stephen R Saklad, Kirk E Evoy
Objective : Pimavanserin is the first United States Food and Drug Administration (FDA)-approved treatment for Parkinson's disease psychosis (PDP). This article reviews the safety, efficacy, and pharmacology data for pimavanserin and its role in therapy. Method of Research: Initial literature sources were identified via MEDLINE search (1946-September 2016) of pimavanserin and ACP-103 (original molecular designation). Reference review and search of FDA.gov and clinicaltrials.gov yielded additional studies. English-language studies of pimavanserin for PDP were evaluated...
February 1, 2018: Innovations in Clinical Neuroscience
https://www.readbyqxmd.com/read/29494265/pharmacological-interventions-for-psychosis-in-parkinson-s-disease-patients
#18
Joseph H Friedman
Psychosis is a common problem for people treated for Parkinson's disease. The syndrome is quite stereotypic, with hallucinations being the most common, followed by delusions. While the hallucinations are usually not very bothersome, the delusions are typically paranoid in nature. Treatment is often, but not always, required. Areas covered: This article reviews the therapeutic approaches of this syndrome focusing on drug treatments used once contributory factors have been removed. This includes a review of the evidence supporting the use of clozapine and, most recently, pimavanserin, the first drug with antipsychotic efficacy that has no effect on dopamine...
April 2018: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/29475576/pharmacological-interventions-for-treating-sialorrhea-associated-with-neurological-disorders-a-mixed-treatment-network-meta-analysis-of-randomized-controlled-trials
#19
REVIEW
Kannan Sridharan, Gowri Sivaramakrishnan
Sialorrhea is a common distress associated with certain neurological disorders. The aim of this study is to compare the pharmacological agents used for treating sialorrhea by network meta-analysis. Electronic databases were searched for randomized clinical trials comparing active drugs with either placebo or other active drugs. Total drooling scores was the primary outcome measure. Inverse variance heterogeneity model was used for both direct and mixed treatment comparison analysis. Twenty one studies were included in the systematic review and 15 in the meta-analysis...
May 2018: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/29462693/two-novel-dual-glp-1-gip-receptor-agonists-are-neuroprotective-in-the-mptp-mouse-model-of-parkinson-s-disease
#20
Peng Feng, Xiangjian Zhang, Dongfang Li, Chenhui Ji, Ziyue Yuan, Ruifang Wang, Guofang Xue, Guanglai Li, Christian Hölscher
Type 2 diabetes mellitus (T2DM) is a risk factors for developing Parkinson's disease (PD). Insulin desensitization is observed in the brains of PD patients, which may be an underlying mechanism that promotes neurodegeneration. Incretin hormones are growth factors that can re-sensitize insulin signalling. We have previously shown that analogues of the incretins GLP-1 or GIP have neuroprotective effects in the MPTP mouse model of PD. Novel dual GLP-1/GIP receptor agonists have been developed as treatments for T2DM...
May 1, 2018: Neuropharmacology
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