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Antiparkinson's drug research

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https://www.readbyqxmd.com/read/26377981/articulation-disorders-and-duration-severity-and-l-dopa-dosage-in-idiopathic-parkinson-s-disease
#1
COMPARATIVE STUDY
Wioletta Pawlukowska, Monika Gołąb-Janowska, Krzysztof Safranow, Iwona Rotter, Katarzyna Amernik, Krystyna Honczarenko, Przemysław Nowacki
BACKGROUND: Parkinson's disease (PD) is one of the most common diseases of the central nervous system (CNS). It is frequently heralded by speech disturbances, which are one of its first symptoms. AIM: The aim of this paper is to share our own experience concerning the correlation between the severity of speech disorders and the PD duration, its severity and the intake of L-dopa. MATERIAL AND METHODS: The research included 93 patients with idiopathic PD, aged 26-86 years (mean age 65...
2015: Neurologia i Neurochirurgia Polska
https://www.readbyqxmd.com/read/25676564/role-of-apomorphine-in-the-treatment-of-parkinson-s-disease
#2
REVIEW
Allison Boyle, William Ondo
Current research shows that apomorphine is an effective treatment for symptoms of Parkinson's Disease (PD). The highly lipophilic structure allows apomorphine to cross cell membranes rapidly, leading to the rapid onset of action for on/off symptoms of PD. The use of apomorphine was limited in the past due to peripheral side effects, but with the advent of better delivery systems and medications to control side effects, apomorphine is better tolerated and more widely in use. The major delivery systems are continuous subcutaneous infusions and intermittent subcutaneous injections, but other delivery routes are under investigation...
February 2015: CNS Drugs
https://www.readbyqxmd.com/read/25527341/initial-management-of-parkinson-s-disease
#3
REVIEW
Christopher G Goetz, Gian Pal
Parkinson's disease is one of the most common neurodegenerative disorders seen in the United States and United Kingdom. The disease is characterised by two processes-cellular degeneration and the resulting biochemical deficiency of dopamine. Although these processes are inter-related, they are approached separately in the clinical setting. Currently, no proven neuroprotective or disease modifying treatment is available for Parkinson's disease. Several agents can be used to treat the motor symptoms associated with dopamine deficiency, and it is important to choose wisely when starting treatment...
December 19, 2014: BMJ: British Medical Journal
https://www.readbyqxmd.com/read/25503824/medication-adherence-in-patients-with-parkinson-s-disease
#4
REVIEW
Naveed Malek, Donald G Grosset
Parkinson's disease (PD) is the second most common neurodegenerative disorder, after Alzheimer's disease, affecting the elderly worldwide. Current therapy for PD is largely based on prescription of drugs that act as either dopamine precursors, dopamine agonists or agents that inhibit key enzymes in the dopamine catabolic pathways. Most of these drugs are administered in tablet or capsule form and can involve multiple daily doses in complex dosing regimens, which contributes to sub-optimal compliance amongst patients...
January 2015: CNS Drugs
https://www.readbyqxmd.com/read/25503261/5-ht1a-receptor-dependent-control-of-nigrostriatal-dopamine-neurotransmission-in-the-pharmacotherapy-of-parkinson-s-disease-and-schizophrenia
#5
REVIEW
Darakhshan J Haleem
Dysfunctions of the basal ganglia are associated with a number of neurological and psychiatric conditions including Parkinson's disease and schizophrenia. Current treatments of these disorders are mostly symptomatic and inadequate, and are often associated with a number of unwanted side-effects. The striatum, the terminal region of the nigrostriatal dopamine pathway, is the main input nucleus of the basal ganglia, and dopamine neurotransmission through the nigrostriatal pathway plays a crucial role in the modulation of basal ganglia output and mediated behaviors...
February 2015: Behavioural Pharmacology
https://www.readbyqxmd.com/read/25491387/the-medical-treatment-of-parkinson-disease-from-james-parkinson-to-george-cotzias
#6
REVIEW
Stanley Fahn
It took exactly 150 years since James Parkinson's description in 1817 of the illness bearing his name until the development of effective therapy for this disorder, namely, the introduction of high-dosage levodopa by George Cotzias in 1967. During the first 50 years, no effective therapy was available, but neurologists reported using different agents, including metals. Then, around 1867, Charcot found solanaceous alkaloids to be somewhat helpful, and these became the accepted and popular therapy for the next 75 years...
January 2015: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/25488030/four-pioneers-of-l-dopa-treatment-arvid-carlsson-oleh-hornykiewicz-george-cotzias-and-melvin-yahr
#7
REVIEW
Andrew J Lees, Eduardo Tolosa, C Warren Olanow
Four individuals stand out as pioneers of the early work that led to levodopa becoming a revolutionary new treatment for Parkinson's disease: Arvid Carlsson, Oleh Hornykiewicz, George C. Cotzias, and Melvin D. Yahr. All four were MDs. The first three had extra training in pharmacology, and in fact did their research in pharmacology. The fourth was a clinical neurologist, the only one in this group with those credentials. The story starts with Carlsson, who became interested in studying the mechanism of reserpine's sedative effect, now recognized as a drug-induced parkinsonian state...
January 2015: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/25457814/cancer-risks-among-the-users-of-ergot-derived-dopamine-agonists-for-parkinson-s-disease-a-nationwide-population-based-survey
#8
Vinchi Wang, Tzu-Hao Chao, Chung-Chih Hsieh, Che-Chen Lin, Chia-Hung Kao
BACKGROUND: Factors of cancer occurrence among Parkinson disease patients are still not well known, although genetic predilection has been investigated. The aim of this study is to evaluate the medication effect of dopamine agonists of Parkinson disease on incidence of cancers from the Taiwan National Health Insurance Research Database. METHODS: We conducted a population-based nested case-control study by using the resources of the Taiwanese National Health Insurance from 1996 to 2000 and analyzed the prevalence of cancer among patients with Parkinson disease...
January 2015: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/25227476/thiazolidinediones-under-preclinical-and-early-clinical-development-for-the-treatment-of-parkinson-s-disease
#9
REVIEW
Anna R Carta, Tanya Simuni
INTRODUCTION: Current treatment of Parkinson's disease (PD) is limited to symptomatic dopaminergic therapy, while no interventions have been shown to slow down disease progression. AREAS COVERED: The following article highlights a group of PPAR-γ agonists called thiazolidinediones (TZDs), which are currently being tested for a putative disease-modifying benefit in PD, using pioglitazone as a prototypic compound. PPAR-γ is highly expressed in neurons of the substantia nigra and CNS immune cells...
February 2015: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/25203719/jnj-40255293-a-novel-adenosine-a2a-a1-antagonist-with-efficacy-in-preclinical-models-of-parkinson-s-disease
#10
John R Atack, Brian C Shook, Stefanie Rassnick, Paul F Jackson, Kenneth Rhodes, Wilhelmus H Drinkenburg, Abdallah Ahnaou, Paula Te Riele, Xavier Langlois, Brian Hrupka, Patrick De Haes, Herman Hendrickx, Nancy Aerts, Koen Hens, Annemie Wellens, Jef Vermeire, Anton A H P Megens
Adenosine A2A antagonists are believed to have therapeutic potential in the treatment of Parkinson's disease (PD). We have characterized the dual adenosine A2A/A1 receptor antagonist JNJ-40255293 (2-amino-8-[2-(4-morpholinyl)ethoxy]-4-phenyl-5H-indeno[1,2-d]pyrimidin-5-one). JNJ-40255293 was a high-affinity (7.5 nM) antagonist at the human A2A receptor with 7-fold in vitro selectivity versus the human A1 receptor. A similar A2A:A1 selectivity was seen in vivo (ED50's of 0.21 and 2.1 mg/kg p.o. for occupancy of rat brain A2A and A1 receptors, respectively)...
October 15, 2014: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/25146568/emerging-drugs-for-levodopa-induced-dyskinesia
#11
REVIEW
Amaal Al Dakheel, Isabelle Beaulieu-Boire, Susan H Fox
INTRODUCTION: Levodopa continues to be the main symptomatic therapy for clinical features of Parkinson's disease. However, prolonged use leads to motor complications, including levodopa-induced dyskinesia (LID). This has debilitating impact on the patients and is a significant challenge for the treating physician. There are currently limited pharmacological options for reducing established LID without causing side effects. Drugs to prevent or delay LID are also an increasing part of the strategy to manage LID, but have yet to show promise...
September 2014: Expert Opinion on Emerging Drugs
https://www.readbyqxmd.com/read/25141900/parkinson-s-disease-pharmacogenomics-new-findings-and-perspectives
#12
Artur F Schumacher-Schuh, Carlos R M Rieder, Mara H Hutz
Parkinson's disease (PD) is unique among neurodegenerative disorders because a highly effective pharmacological symptomatic treatment is available. The marked variability in drug response and in adverse profiles associated with this treatment led to the search of genetic markers associated with these features. We present a review of the literature on PD pharmacogenetics to provide a critical discussion of the current findings, new approaches, limitations and recommendations for future research. Pharmacogenetics studies in this field have assessed several outcomes and genes, with special focus on dopaminergic genes, mainly DRD2, which is the most important receptor in nigrostriatal pathway...
June 2014: Pharmacogenomics
https://www.readbyqxmd.com/read/25096413/advances-in-drug-development-for-parkinson-s-disease-present-status
#13
REVIEW
Dibbanti Harikrishna Reddy, Shubham Misra, Bikash Medhi
The major hallmark of Parkinson's disease (PD) is the progressive loss of dopaminergic neurons in the substantia nigra pars compacta, leading to the characteristic motor symptoms of resting tremors, bradykinesia and rigidity. Research in the field of PD therapy has been partly successful in terms of developing symptomatic treatments, but it also experienced several failures with regard to developing disease-modifying therapies. According to the definition of the Committee to Identify Neuroprotective Agents for Parkinson's, neuroprotection would be any intervention that favorably influences the disease process or underlying pathogenesis to produce enduring benefits for patients...
2014: Pharmacology
https://www.readbyqxmd.com/read/25080284/stimulation-of-the-pedunculopontine-nucleus-area-in-parkinson-s-disease-effects-on-speech-and-intelligibility
#14
RANDOMIZED CONTROLLED TRIAL
Serge Pinto, Murielle Ferraye, Robert Espesser, Valérie Fraix, Audrey Maillet, Jennifer Guirchoum, Deborah Layani-Zemour, Alain Ghio, Stéphan Chabardès, Pierre Pollak, Bettina Debû
Improvement of gait disorders following pedunculopontine nucleus area stimulation in patients with Parkinson's disease has previously been reported and led us to propose this surgical treatment to patients who progressively developed severe gait disorders and freezing despite optimal dopaminergic drug treatment and subthalamic nucleus stimulation. The outcome of our prospective study on the first six patients was somewhat mitigated, as freezing of gait and falls related to freezing were improved by low frequency electrical stimulation of the pedunculopontine nucleus area in some, but not all, patients...
October 2014: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/24960254/mavoglurant-as-a-treatment-for-parkinson-s-disease
#15
REVIEW
Dmitry Petrov, Ignacio Pedros, Maria Luisa de Lemos, Mercè Pallàs, Anna Maria Canudas, Alberto Lazarowski, Carlos Beas-Zarate, Carme Auladell, Jaume Folch, Antoni Camins
INTRODUCTION: A major unresolved issue in the Parkinson's disease (PD) treatment is the development of l-DOPA-induced dyskinesias (LIDs) as a side effect of chronic L-DOPA administration. Currently, LIDs are managed in part by reducing the L-DOPA dose or by the administration of amantadine. However, this treatment is only partially effective. A potential strategy, currently under investigation, is the coadministration of metabotropic glutamate receptor 5 (mGluR5) negative allosteric modulators (NAMs) and L-DOPA; a treatment that results in the improvement of dyskinesia symptoms and that permits reductions in l-DOPA dosage frequency...
August 2014: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/24928805/long-term-effectiveness-of-dopamine-agonists-and-monoamine-oxidase-b-inhibitors-compared-with-levodopa-as-initial-treatment-for-parkinson-s-disease-pd-med-a-large-open-label-pragmatic-randomised-trial
#16
RANDOMIZED CONTROLLED TRIAL
Richard Gray, Natalie Ives, Caroline Rick, Smitaa Patel, Alastair Gray, Crispin Jenkinson, Emma McIntosh, Keith Wheatley, Adrian Williams, Carl E Clarke
BACKGROUND: Whether initial treatment for Parkinson's disease should consist of levodopa, dopamine agonists, or monoamine oxidase type B inhibitors (MAOBI) is uncertain. We aimed to establish which of these three classes of drug, as initial treatment, provides the most effective long-term control of symptoms and best quality of life for people with early Parkinson's disease. METHODS: In this pragmatic, open-label randomised trial, patients newly diagnosed with Parkinson's disease were randomly assigned (by telephone call to a central office; 1:1:1) between levodopa-sparing therapy (dopamine agonists or MAOBI) and levodopa alone...
September 27, 2014: Lancet
https://www.readbyqxmd.com/read/24920904/increased-antiparkinson-efficacy-of-the-combined-administration-of-vegf-and-gdnf-loaded-nanospheres-in-a-partial-lesion-model-of-parkinson-s-disease
#17
Enara Herrán, Catalina Requejo, Jose Angel Ruiz-Ortega, Asier Aristieta, Manoli Igartua, Harkaitz Bengoetxea, Luisa Ugedo, Jose Luis Pedraz, Jose Vicente Lafuente, Rosa Maria Hernández
Current research efforts are focused on the application of growth factors, such as glial cell line-derived neurotrophic factor (GDNF) and vascular endothelial growth factor (VEGF), as neuroregenerative approaches that will prevent the neurodegenerative process in Parkinson's disease. Continuing a previous work published by our research group, and with the aim to overcome different limitations related to growth factor administration, VEGF and GDNF were encapsulated in poly(lactic-co-glycolic acid) nanospheres (NS)...
2014: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/24720843/effects-of-6-hydroxydopamine-exposure-on-motor-activity-and-biochemical-expression-in-zebrafish-danio-rerio-larvae
#18
Chien-Wei Feng, Zhi-Hong Wen, Shi-Ying Huang, Han-Chun Hung, Chun-Hong Chen, San-Nan Yang, Nan-Fu Chen, Hui-Min Wang, Chung-Der Hsiao, Wu-Fu Chen
Parkinson's disease (PD) is a neurodegenerative disease that is characterized by the progressive loss of dopaminergic (DA) neurons in the substantia nigra. However, current treatments for PD are mainly palliative. Recently, researchers discovered that neurotoxins can induce Parkinsonian-like symptoms in zebrafish. No study to date has investigated the characteristics of PD, such as neuroinflammation factors, oxidative stress, or ubiquitin dysfunction, in this model. Therefore, the current study was aimed at utilizing commonly used clinical drugs, minocycline, vitamin E, and Sinemet, to test the usefulness of this model...
June 2014: Zebrafish
https://www.readbyqxmd.com/read/24687255/adenosine-a2a-receptor-antagonists-in-parkinson-s-disease-progress-in-clinical-trials-from-the-newly-approved-istradefylline-to-drugs-in-early-development-and-those-already-discontinued
#19
REVIEW
Annalisa Pinna
Neurotransmitters other than dopamine, such as norepinephrine, 5-hydroxytryptamine, glutamate, adenosine and acetylcholine, are involved in Parkinson's disease (PD) and contribute to its symptomatology. Thus, the progress of non-dopaminergic therapies for PD has attracted much interest in recent years. Among new classes of drugs, adenosine A2A antagonists have emerged as promising candidates. The development of new highly selective adenosine A2A receptor antagonists, and their encouraging anti-parkinsonian responses in animal models of PD, has provided a rationale for clinical trials to evaluate the therapeutic potential and the safety of these agents in patients with PD...
May 2014: CNS Drugs
https://www.readbyqxmd.com/read/24673462/two-new-adenosine-receptor-antagonists-for-the-treatment-of-parkinson-s-disease-istradefylline-versus-tozadenant
#20
REVIEW
Santiago Perez-Lloret, Marcelo Merello
INTRODUCTION: Adenosine A2A receptors are localized in the brain, mainly within the caudate and putamen nuclei of the basal ganglia. Their activation leads to stimulation of the 'indirect' pathway. Conversely, administration of A2A receptor antagonists leads to inhibition of this pathway, which was translated into reduced hypomotility in several animal models of parkinsonism. AREAS COVERED: In this review, the effects of two A2A receptor antagonists, istradefylline and tozadenant, on parkinsonian symptoms in animal and humans will be discussed...
June 2014: Expert Opinion on Pharmacotherapy
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