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Parkinson drugs trials

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https://www.readbyqxmd.com/read/28025940/a-mini-review-on-the-chemistry-and-neuroprotective-effects-of-silymarin
#1
Kasi Pandima Devi, Dicson Sheeja Malar, Nady Braidy, Seyed Mohammad Nabavi, Seyed Fazel Nabavi
The plant milk thistle and silymarin has been traditionally used as a natural remedy for the treatment of various ailments including neurological disorders such Alzheimer's and Parkinson's Disease and cerebral ischemia for over 2000 years. The neuroprotective effects conferred by silymarin include modulation of various antioxidant mechanisms, and several kinases involved in cell signaling pathways, inhibition of the inflammatory response generated during neurodegeneration, neurotropic effects, regulation of neurotransmitters and inhibition of apoptosis...
December 27, 2016: Current Drug Targets
https://www.readbyqxmd.com/read/27999408/cyclodextrins-as-emerging-therapeutic-tools-in-the-treatment-of-cholesterol-associated-vascular-and-neurodegenerative-diseases
#2
REVIEW
Caroline Coisne, Sébastien Tilloy, Eric Monflier, Daniel Wils, Laurence Fenart, Fabien Gosselet
Cardiovascular diseases, like atherosclerosis, and neurodegenerative diseases affecting the central nervous system (CNS) are closely linked to alterations of cholesterol metabolism. Therefore, innovative pharmacological approaches aiming at counteracting cholesterol imbalance display promising therapeutic potential. However, these approaches need to take into account the existence of biological barriers such as intestinal and blood-brain barriers which participate in the organ homeostasis and are major defense systems against xenobiotics...
December 20, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27979722/apomorphine-pharmacological-properties-and-clinical-trials-in-parkinson-s-disease
#3
Peter Jenner, Regina Katzenschlager
Apomorphine is often considered an archetypal dopamine agonist used in the treatment of Parkinson's disease (PD). However, it can be clearly differentiated from most other commonly used dopamine agonists on the basis of its pharmacology and on its unique clinical profile. Like levodopa and dopamine, apomorphine acts as a potent, direct and broad spectrum dopamine agonist activating all dopamine receptor subtypes. It also has affinity for serotonin receptors, and α-adrenergic receptors. Apomorphine is usually titrated to a dose that provides an equivalent antiparkinsonian response to that provided by levodopa, and its subcutaneous delivery allows a rapid onset of action, usually within 7-10 min...
December 2016: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/27965247/can-commonly-prescribed-drugs-be-repurposed-for-the-prevention-or-treatment-of-alzheimer-s-and-other-neurodegenerative-diseases-protocol-for-an-observational-cohort-study-in-the-uk-clinical-practice-research-datalink
#4
Venexia M Walker, Neil M Davies, Tim Jones, Patrick G Kehoe, Richard M Martin
INTRODUCTION: Current treatments for Alzheimer's and other neurodegenerative diseases have only limited effectiveness meaning that there is an urgent need for new medications that could influence disease incidence and progression. We will investigate the potential of a selection of commonly prescribed drugs, as a more efficient and cost-effective method of identifying new drugs for the prevention or treatment of Alzheimer's disease, non-Alzheimer's disease dementias, Parkinson's disease and amyotrophic lateral sclerosis...
December 13, 2016: BMJ Open
https://www.readbyqxmd.com/read/27917685/phosphodiesterase-10-inhibitors-in-clinical-development-for-cns-disorders
#5
Hugo Geerts, Athan Spiros, Patrick Roberts
Phosphodiesterase 10 inhibitors (PDE10-I), are conceptually attractive drugs with a potential great therapeutic window as their enriched striatal localization may likely stimulate D1R and reduce D2R downstream effects. However, so far selective PDE10-I with efficacy in animal models have not shown benefit in clinical trials and unexpectedly revealed a substantial dyskinesia motor side-effect. Areas covered: This paper reviews the underlying biological rationale of PDE10 as a target in schizophrenia, Parkinson's and Huntington's disease based on peer-reviewed published articles, the status of the different PDE10-I in clinical development for various CNS indications and explores possible reasons for the clinical trial failures and translational disconnect...
December 10, 2016: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/27902767/towards-a-non-human-primate-model-of-alpha-synucleinopathy-for-development-of-therapeutics-for-parkinson-s-disease-optimization-of-aav1-2-delivery-parameters-to-drive-sustained-expression-of-alpha-synuclein-and-dopaminergic-degeneration-in-macaque
#6
James B Koprich, Tom H Johnston, Gabriela Reyes, Vanessa Omana, Jonathan M Brotchie
Recent failures in clinical trials for disease modification in Parkinson's disease have highlighted the need for a non-human primate model of the synucleinopathy underpinning dopaminergic neuron degeneration. The present study was defined to begin the development of such a model in cynomolgus macaque. We have validated surgical and vector parameters to define a means to provide a robust over-expression of alpha-synuclein which is associated with Lewy-like pathology and robust degeneration of the nigrostriatal pathway...
2016: PloS One
https://www.readbyqxmd.com/read/27869056/why-calpain-inhibitors-are-interesting-leading-compounds-to-search-for-new-therapeutic-options-to-treat-leishmaniasis
#7
Vitor Ennes-Vidal, Rubem Figueiredo Sadock Menna-Barreto, Marta Helena Branquinha, André Luis Souza Dos Santos, Claudia Masini D'Avila-Levy
Leishmaniasis is a neglected disease, which needs improvements in drug development, mainly due to the toxicity, parasite resistance and low compliance of patients to treatment. Therefore, the development of new chemotherapeutic compounds is an urgent need. This opinion article will briefly highlight the feasible use of calpain inhibitors as leading compounds to search for new therapeutic options to treat leishmaniasis. The milestone of this approach is to take advantage on the myriad of inhibitors developed against calpains, some of which are in advanced clinical trials...
November 21, 2016: Parasitology
https://www.readbyqxmd.com/read/27866808/combined-beta-glucosylceramide-and-ambroxol-hydrochloride-in-patients-with-gaucher-related-parkinson-disease-from-clinical-observations-to-drug-development
#8
Yuval Ishay, Ari Zimran, Jeffrey Szer, Tama Dinur, Yaron Ilan, David Arkadir
Both patients with non-neuronopathic Gaucher disease (GD) and heterozygous GBA mutation carrier are at increased risk for Parkinson disease (PD). The risk for PD in these groups does not linearly increase with glucosylceramide (GC) accumulation or with acid β-glucocerebrosidase (GCase) activity. This observation, together with other clinical systemic observations raises the possibility that extra-cellular GC actually has beneficial, anti-inflammatory, properties. Based on this hypothesis, we suggest here that the administration of supplementary oral GC to GBA carriers at risk for PD may slow inflammatory-driven secondary neuronal death...
November 12, 2016: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/27865667/lower-urinary-tract-symptoms-in-parkinson-s-disease-prevalence-aetiology-and-management
#9
REVIEW
Claire McDonald, Kristian Winge, David J Burn
Lower urinary tract symptoms (LUTS) are common in Parkinson's disease (PD), effecting 27-85% of patients with PD. Irritative symptoms predominate and urodynamic studies confirm high prevalence of detrusor overactivity in PD. LUTS are present early in PD and are more common in PD than in age matched controls. The assessment of LUTS in PD is complicated by coexisting bradykinesia and cognitive impairment. Although LUTS become more troublesome as PD progresses it remains unclear if LUTS severity correlates with motor symptoms and/or duration of PD...
November 1, 2016: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/27859866/modelling-idiopathic-parkinson-disease-as-a-complex-illness-can-inform-incidence-rate-in-healthy-adults-the%C3%A2-pr-edigt-score
#10
Michael G Schlossmacher, Julianna J Tomlinson, Goncalo Santos, Bojan Shutinoski, Earl G Brown, Douglas Manuel, Tiago Mestre
Fifty-five years after the concept of dopamine replacement therapy was introduced, Parkinson disease (PD) remains an incurable neurological disorder. To date, no disease-modifying therapeutic has been approved. The inability to predict PD incidence risk in healthy adults is seen as a limitation in drug development, because by the time of clinical diagnosis ≥ 60% of dopamine neurons have been lost. We have designed an incidence prediction model founded on the concept that the pathogenesis of PD is similar to that of many disorders observed in ageing humans, i...
January 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/27830492/transcranial-magnetic-stimulation-for-the-assessment-of-neurodegenerative-disease
#11
REVIEW
Steve Vucic, Matthew C Kiernan
Transcranial magnetic stimulation (TMS) is a noninvasive technique that has provided important information about cortical function across an array of neurodegenerative disorders, including Alzheimer's disease, frontotemporal dementia, Parkinson's disease, and related extrapyramidal disorders. Application of TMS techniques in neurodegenerative diseases has provided important pathophysiological insights, leading to the development of pathogenic and diagnostic biomarkers that could be used in the clinical setting and therapeutic trials...
November 9, 2016: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/27826740/calcium-channel-antagonists-as-disease-modifying-therapy-for-parkinson-s-disease-therapeutic-rationale-and-current-status
#12
Tara Swart, Michael J Hurley
Parkinson's disease is a disabling hypokinetic neurological movement disorder in which the aetiology is unknown in the majority of cases. Current pharmacological treatments, though effective at restoring movement, are only symptomatic and do nothing to slow disease progression. Electrophysiological, epidemiological and neuropathological studies have implicated CaV1.3 subtype calcium channels in the pathogenesis of the disorder, and drugs with some selectivity for this ion channel (brain-penetrant dihydropyridine calcium channel blockers) are neuroprotective in animal models of the disease...
November 8, 2016: CNS Drugs
https://www.readbyqxmd.com/read/27819412/harnessing-cerebrospinal-fluid-biomarkers-in-clinical-trials-for-treating-alzheimer-s-and-parkinson-s-diseases-potential-and-challenges
#13
REVIEW
Dana Kim, Young Sam Kim, Dong Wun Shin, Chang Shin Park, Ju Hee Kang
No disease-modifying therapies (DMT) for neurodegenerative diseases (NDs) have been established, particularly for Alzheimer's disease (AD) and Parkinson's disease (PD). It is unclear why candidate drugs that successfully demonstrate therapeutic effects in animal models fail to show disease-modifying effects in clinical trials. To overcome this hurdle, patients with homogeneous pathologies should be detected as early as possible. The early detection of AD patients using sufficiently tested biomarkers could demonstrate the potential usefulness of combining biomarkers with clinical measures as a diagnostic tool...
October 2016: Journal of Clinical Neurology
https://www.readbyqxmd.com/read/27802242/effects-of-safinamide-on-pain-in-fluctuating-parkinson-s-disease-patients-a-post-hoc-analysis
#14
Carlo Cattaneo, Paolo Barone, Erminio Bonizzoni, Marco Sardina
BACKGROUND: Pain, a frequent non-motor symptom in Parkinson's Disease (PD), significantly impacts on quality of life. Safinamide is a new drug with dopaminergic and non-dopaminergic properties, approved in Europe as adjunct therapy to levodopa for the treatment of fluctuating PD patients. Results from two 24-month, double-blind, placebo-controlled studies demonstrated that safinamide has positive effects on both motor functions and quality of life in PD patients. OBJECTIVE: To investigate the effects of safinamide on pain management in PD patients with motor fluctuations using pooled data from studies 016 and SETTLE...
October 11, 2016: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/27774496/parkinson-s-impulse-control-scale-for-the-severity-rating-of-impulse-control-behaviors-in-parkinson-s-disease-a-semistructured-clinical-assessment-tool
#15
David Okai, Sally Askey-Jones, Joel Mack, Anne Martin, Kallol Ray Chaudhuri, Michael Samuel, Anthony S David, Richard G Brown
BACKGROUND: Impulse-control behaviors (ICBs) are increasingly recognized in Parkinson's disease (PD) as drug-related effects of dopaminergic mediation that occur in 15% to 35% of patients with PD. The authors describe the design and evaluation of a new, clinician-rated severity scale for the assessment of syndromal and subsyndromal forms of impulse-control disorders (ICDs), simple (punding) and complex (hobbyism) repetitive behaviors, and compulsive overuse of medication (dopamine dysregulation syndrome)...
September 2016: Movement Disorders Clinical Practice
https://www.readbyqxmd.com/read/27714426/chronic-administration-of-the-dopamine-d2-3-agonist-ropinirole-invigorates-performance-of-a-rodent-slot-machine-task-potentially-indicative-of-less-distractible-or-compulsive-like-gambling-behaviour
#16
Paul J Cocker, M Tremblay, S Kaur, Catharine A Winstanley
RATIONALE: Whilst dopamine agonist therapies can successfully manage the symptoms of diseases such as Parkinson's disease (PD), fibromyalgia and restless leg syndrome, they can also cause impulse control and addiction disorders such as gambling disorder (GD). These compulsive behaviours seriously undermine the utility of such treatments. OBJECTIVES: The objective of the study was to model this phenomenon using a rodent slot machine task (rSMT) in order to investigate the neurobiological basis underlying such behavioural changes...
January 2017: Psychopharmacology
https://www.readbyqxmd.com/read/27713036/insulin-resistance-and-parkinson-s-disease-a-new-target-for-disease-modification
#17
REVIEW
D Athauda, T Foltynie
There is growing evidence that patients with Type 2 diabetes have an increased risk of developing Parkinson's disease and share similar dysregulated pathways suggesting common underlying pathological mechanisms. Historically insulin was thought solely to be a peripherally acting hormone responsible for glucose homeostasis and energy metabolism. However accumulating evidence indicates insulin can cross the blood-brain-barrier and influence a multitude of processes in the brain including regulating neuronal survival and growth, dopaminergic transmission, maintenance of synapses and pathways involved in cognition...
October 2016: Progress in Neurobiology
https://www.readbyqxmd.com/read/27686862/neural-stem-cell-tumorigenicity-and-biodistribution-assessment-for-phase-i-clinical-trial-in-parkinson-s-disease
#18
Ibon Garitaonandia, Rodolfo Gonzalez, Trudy Christiansen-Weber, Tatiana Abramihina, Maxim Poustovoitov, Alexander Noskov, Glenn Sherman, Andrey Semechkin, Evan Snyder, Russell Kern
Human pluripotent stem cells (PSC) have the potential to revolutionize regenerative medicine. However undifferentiated PSC can form tumors and strict quality control measures and safety studies must be conducted before clinical translation. Here we describe preclinical tumorigenicity and biodistribution safety studies that were required by the US Food and Drug Administration (FDA) and Australian Therapeutic Goods Administration (TGA) prior to conducting a Phase I clinical trial evaluating the safety and tolerability of human parthenogenetic stem cell derived neural stem cells ISC-hpNSC for treating Parkinson's disease (ClinicalTrials...
September 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27665574/clinical-pharmacokinetics-and-pharmacodynamics-of-safinamide
#19
Thomas Müller, Paul Foley
The symptoms of Parkinson's disease (PD) reflect disruptions of a number of brain neurotransmitter systems of varying type and degree. Pharmacological agents with multiple neurochemical mechanisms of action are therefore promising candidates for countering these problems and providing comprehensive symptomatic relief for patients. The pharmacological profile of safinamide includes reversible monoamine oxidase B inhibition, blockage of voltage-dependent Na(+) channels, modulation of Ca(2+) channels, and inhibition of glutamate release...
September 24, 2016: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/27664323/subacute-toxicity-evaluation-of-kr-33493-faf1-inhibitor-for-a-new-anti-parkinson-s-disease-agent-after-oral-administration-in-rats-and-dogs
#20
Jong-Woo Jeong, Changsun Yu, Jong-Hwa Lee, Kyoung-Sik Moon, Eunhee Kim, Sung-Eun Yoo, Tae-Sung Koo
KR33493, a newly developed FAS-associated factor 1 (FAF1) inhibitor for Parkinson's disease, is being evaluated in a Phase I clinical trial. In the present study, the subchronic toxicity of KR33493 in Sprague-Dawley (SD) rats and beagle dogs was investigated at various oral doses for 28 and 14 days, respectively. During the study, food consumption, body weights, organ weights, gross findings, and mortality were examined; and ophthalmoscopy, electrocardiography, hematology, serum biochemistry, urinalysis, histopathology, and toxicokinetics were performed...
November 2016: Regulatory Toxicology and Pharmacology: RTP
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