levodopa

..The role of this pathological adaptation and of the consequent changes in signaling in the development and expression of LID are discussed...

..drug regimens for Parkinson's disease (PD) is complicated by the different dose intensities used: higher doses of levodopa and, possibly, other drugs produce better symptomatic control but more late complications...

..Although the short-term benefits of bilateral stimulation of the subthalamic nucleus in patients with advanced Parkinson's disease have been well documented, the long-term outcomes of the procedure are unknown...

..consensus regarding the frequency (and hence, the risk), of dyskinesias or motor fluctuations during chronic levodopa therapy for Parkinson's disease (PD)...

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..We conclude that dopamine-dependent modulation of striatal activity can account for how the human brain uses reward prediction errors to improve future decisions...

To assess the effect of a single levodopa dose (200 mg levodopa, 50 mg carbidopa=sdLD) on cortical and subcortical motor-circuit activation during bimanual grip force in patients with Parkinson's disease (PD).

..This might be important for the therapeutic application of dopaminergic agents, especially for rehabilitative purposes, and explain some opposing results in former studies...

..correlations between the suppression of synchronization at 8-35 Hz in STN and the reduction in Parkinsonism with levodopa. LFPs were recorded on and off medication from STN deep-brain stimulation electrodes in nine PD patients...

..Due to its treatment-dependent expression, and strong correlation with the associated dyskinetic symptoms, striatal PDyn mRNA, in particular, may play a role in the mechanisms of behavioural sensitization brought about by the drug...

..This study shows that, by contrast with levodopa, STN stimulation improves memory guided saccade deficits, and illustrates for the first time in humans the role ..

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..Our aim was to ascertain whether levodopa could enhance the efficacy of physiotherapy after hemiplegia.

..The best way to initiate dopaminergic therapy for early Parkinson disease remains unclear...

..These observations suggest that the generation of neural precursor cells is impaired in Parkinson disease as a consequence of dopaminergic denervation...

..proportion of patients with Parkinson's disease (PD) receiving dopamine replacement therapy in the form of levodopa develop dyskinesia that becomes a major complicating factor in treatment...

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The impact of motor complications of Parkinson's disease (PD), especially levodopa-induced dyskinesias, on quality of life (QL) was studied in 143 patients with PD...

..The present results indicate that both a high DA release post-L-DOPA administration and an increased responsiveness to DA must coexist for a full expression of dyskinesia...

Striatal serotonin projections have been implicated in levodopa-induced dyskinesia by providing an unregulated source of dopamine release...

..We studied 22 families with a phenotype of levodopa-responsive dystonia by sequencing the six coding exons, the 5'-untranslated region and the exon-intron boundaries ..

..These data provide an estimate of the magnitude of the treatment effects and emphasize the need for controlled and randomized studies...

..This indicates the importance of studying DA release dynamics for the understanding of both beneficial and adverse effects of l-DOPA replacement therapy...

..In a double-blind, placebo-controlled within-subject design, subjects were measured after levodopa (100 mg) or placebo administration...

Several in vitro studies have suggested levodopa (L-dopa) to be toxic to dopaminergic neurons and that it can modulate the aggregation process of α-synuclein...

Evidence for an involvement of striatal D1 receptors in levodopa-induced dyskinesia has been presented whereas the contribution of striatal D2 receptors remains controversial...

..disease is mainly characterized by a dysfunction of the sensorimotor pathways, which can be influenced by levodopa administration, the present study investigated the functional connectivity changes within the sensorimotor ..

..nanocomposite material with an anti-parkinsonian active compound, L-3-(3,4-dihydroxyphenyl) alanine (levodopa), intercalated into the inorganic interlayers of a Zn/Al-layered double hydroxide (LDH) was synthesized using a ..

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..emission tomography (PET) suggested a slower loss of striatal dopamine storage with ropinirole compared with levodopa. This prospective, 2-year, randomized, double-blind, multinational study compared the rates of loss of dopamine-..

..The data suggest that alterations in the expression and subcellular distribution of arrestins and GRKs contribute to pathophysiology of Parkinson's disease. Thus, these proteins may be targets for antiparkinsonian therapy...

b>Levodopa-induced dyskinesia can result in significant functional disability and reduced quality of life in patients with Parkinson's disease (PD)...

..objectives were to assess the efficacy, safety, and tolerability of AFQ056 in Parkinson's disease patients with levodopa-induced dyskinesia...

..These findings implicate independent mechanisms leading to impulsivity in treated Parkinson's patients and were predicted by a single neurocomputational model of the basal ganglia...

..Taken together these results show that vector-mediated continuous 3,4-dihydroxyphenylalanine delivery has the potential to provide significant symptomatic relief even in advanced stages of Parkinson's disease...

b>Levodopa (L-dopa) and subthalamic nucleus (STN) stimulation treatments have been associated with both improvement and exacerbation of dysarthria in Parkinson's disease (PD)...

To assess the effect of levodopa on distinct freezing of gait (FOG) subtypes in patients with 'off' FOG. Nineteen patients (12 men, mean age 62.0 +/- 8...

..Such deficits can be quantified using novel and relatively simple testing procedures, whereas rotometry cannot discriminate between dyskinetic and antiakinetic effects of antiparkinsonian treatments...

..An association between dopamine-replacement therapies and impulse control disorders (ICDs) in Parkinson disease (PD) has been suggested in preliminary studies...

..These data suggest that L-dopa ameliorates high-level cognitive deficits in Parkinson's disease by inducing relative blood flow changes in the right dorsolateral prefrontal cortex...

..The study also suggests that LFP beta oscillatory activity is generated largely within the dorsal portion of the STN and can produce synchronous oscillatory activity of the local neuronal population...

..Thus, increasing dopamine levels with levodopa selectively boosted striatal and substantia nigra/ventral tegmental representations associated with actions ..

..that glutamatergic receptor blockade may improve the motor response complications associated with long-term levodopa treatment in Parkinson's disease (PD) patients...

Involuntary movements, or dyskinesia, represent a debilitating complication of levodopa therapy for Parkinson's disease...

..the efficacy, safety, and tolerability of istradefylline 20 mg once daily versus placebo as an adjunct to levodopa in subjects with Parkinson's disease (PD) who have motor fluctuations...

..to falls, we quantitatively evaluated: (1) the relationship between gait variability (a marker of fall risk in other populations), fall history, and other parkinsonian features, and (2) the effects of levodopa on these relationships.

To compare daytime intraduodenal levodopa/carbidopa infusion as monotherapy with individually optimized conventional combination therapies in patients with advanced Parkinson disease (PD) for motor fluctuations and quality of life (QoL).

..We discuss the implications for investigation and optimal treatment of this common condition at different stages of disease...

..We have developed a model of L-DOPA-induced dyskinesias in mice that reproduces the main clinical features of dyskinesia in humans...

..The combination of nigral denervation and drug treatment establishes inappropriate signalling between the motor cortex and the striatum, leading to persistent dyskinesia...

..We suggest that plasticity in dopamine quantal seems likely to be involved in both normal synaptic modification and disease states...

..This organization is critically dependent on the level of dopaminergic activity...

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..The L-DOPA-induced overexpression of GLT1 may represent a compensatory mechanism involving astrocytes to limit glutamate overactivity and subsequent toxic processes...

..The dyskinetic patients received significantly higher maximum level daily dose of levodopa. These patients had lost weight during the course of the disease from 72+/-15 to 66+/-17kg, p=0.002...

Patients with Parkinson's disease who develop disabling levodopa-induced motor fluctuations have a stronger therapeutic response than those who experience a more modest but stable response...

We studied the effects of subthalamic nucleus (STN) stimulation vs levodopa on freezing of gait (FOG) and gait impairments in a large consecutive series of patients with Parkinson disease with bilateral STN stimulation.

We report here on the experience with continuous jejunal levodopa infusion in 13 German parkinsonian patients who have motor and nonmotor complications despite individually optimized oral treatment...

..To shed light on the effect of levodopa on these network interactions, we investigated 10 patients with tremor-dominant PD and reanalyzed data in 11 ..

..To elucidate molecular mechanisms that underlie the persisting alterations in motor response occurring with levodopa treatment of parkinsonian patients, we evaluated the effects of unilateral nigrostriatal depletion with 6-..

..We sought to examine the prevalence of PN in a population of IPD patients and a potential relationship to levodopa use and fasting methylmalonic acid (MMA) levels.

b>Levodopa has been shown to produce analgesia in various clinical and experimental settings, but its use for chronic pain treatment has not been established...

b>Levodopa is the most effective drug for the treatment of Parkinson's disease. However, the long-term use of this dopamine precursor is complicated by highly disabling fluctuations and dyskinesias...

b>Levodopa-induced dyskinesias are a common complication of long-term therapy in Parkinson's disease...

b>Levodopa-induced dyskinesias represent disabling complications from long-term therapy with dopaminergic drugs for treating Parkinson's disease (PD)...

..Thus, the dopamine overflow produced from the serotonergic nerve fibers appears not to be the major cause of dyskinetic behavior...

Human retinal pigment epithelial (RPE) cells produce levodopa and their transplantation into the striatum might improve continuity of administration compared with that achieved with oral levodopa...

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..The fMRI was carried out after an overnight withdrawal of levodopa (OFF condition): (i) before and (ii) within three days after surgery in absence of neurostimulation...

The Stalevo Reduction in Dyskinesia Evaluation in Parkinson's Disease (STRIDE-PD) study compared the initiation of levodopa (l-dopa) therapy with l-dopa/carbidopa (LC) versus l-dopa/carbidopa/entacapone (LCE) in patients with Parkinson's ..

..These predicted absorption spectra of X1 and X2 showed striking resemblances to those of AADC complexed with dihydroxyphenylacetic acid (DOPAc) and L-dopa methyl ester (DopaOMe), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)..

..were recorded at rest both before (off) and after (on) acute administration of different antiparkinsonian drugs: levodopa, apomorphine, or orphenadrine...

..Our data confirm the role of glutamatergic neurotransmission in the pathogenesis of dyskinesias and the potential of mGluR5 antagonists in the treatment of l-DOPA-induced dyskinesias...

b>Levodopa is the most effective agent to alleviate motor dysfunction in Parkinson's disease but its long-term use is associated with the development of dyskinesias...

..These current findings reveal the integral contribution of the RRN in the development and expression of LID and implicate a prominent role for dorsal raphe 5-HT1AR in the efficacious properties of 5-HT1AR agonists...

..The relation of kinesthetic threshold to disease progression as measured by UPDRS and the effect of levodopa treatment on kinesthesia were assessed in 12 PD compared to age-matched controls...

..Clinically, progression of PD is also characterised by onset of motor complications (MC). MC results from the peripheral and central degree of fluctuations of levodopa (LD) and of dopamine.

..These data confirm the antidyskinetic potential of topiramate and suggest that combination with low-dose amantadine may allow better reduction of dyskinesia with no adverse motor effects...

..These results support the hypothesis that serotonergic neurons are primarily responsible for the storage and release of DA derived from exogenous L-DOPA in the absence of dopaminergic neurons...

..were no significant differences between the twins in bilateral BG-cortical pathways, either basally or after levodopa, whereas the PD-twin had relatively increased activity in the cerebellar-cortical pathways basally that was ..

..PD) continue to experience motor fluctuations and dyskinesias despite the association of dopamine agonists and levodopa with COMT or MAO-B inhibitors...

..This observation is consistent with modeling studies, which demonstrated that dopamine increases the signal-to-noise ratio at the neuronal level with a resultant focusing of representations at the macroscopic level...

..This supports the therapeutic use of an mGluR5 antagonist to restore normal brain glutamate neurotransmission in PD and decrease dyskinesias...

..to discontinuous or pulsatile, stimulation of striatal dopamine receptors will delay or prevent the onset of levodopa-related motor complications...

b>Levodopa/Carbidopa intestinal gel infusion (LCIG) for Parkinson's disease is under debate to provoke polyneuropathy (PNP)...

..The aim of this study was to determine if subthalamotomy is effective in treating advanced Parkinson disease (PD)...

..whether STN stimulation has an influence on functions of the ANS and to compare these effects to those induced by levodopa. Blood pressure (BP) and heart rate (HR) during rest and orthostatic conditions, HR variability (HRV) and ..

..To assess the impact of different surgical targets and techniques, such as ablation and deep brain stimulation, to treat patients with L-dopa-induced dyskinesia (LID), a major therapeutic complication of Parkinson's disease...

The main lesion in Parkinson disease (PD) is loss of substantia nigra dopaminergic neurons. Levodopa (L-DOPA) is the most widely used therapy, but it does not arrest disease progression...

..These findings indicate a novel anti-dyskinetic mechanism of action for 5-HT(1A)R agonists with implications for the improved treatment of Parkinson's disease...

..dystonia) is a dystonia with onset in childhood that shows a marked response without any side effects to levodopa. Recently the gene for dopa responsive dystonia (DRD) was mapped to chromosome 14q...

..g. wearing-off and levodopa-induced dyskinesia) have identified 5-HT1A, 5-HT1B and 5-HT2C receptors as potential therapeutic targets in ..

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..Few data on the effects of levodopa on prosody, more specifically on the effects on the variability of prosodic characteristics such as pitch, ..

Dysregulation of dopamine receptors is thought to underlie levodopa-induced dyskinesias in experimental models of Parkinson's disease...

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..DeltaFosB overexpression reproduced the entire spectrum of altered motor behaviors in response to acute levodopa tests, including different types of abnormal involuntary movements and hypersensitivity of rotational responses ..

..Recent studies have suggested that non-physiological release of dopamine (DA) formed from levodopa in these serotoninergic terminals underlies abnormal involuntary movement (AIMs) induction in 6-OHDA lesioned ..

..L-dihydroxyphenylalanine (levodopa, L-DOPA) is the drug of choice for treatment of the symptoms of this disease, serving to replenish dopamine...

DESCRIPTION (provided by applicant): This study will investigate the efficacy of levodopa in improving the neurodevelopment and movement disorders in children with Angelman Syndrome (AS), a rare neurodevelopmental disorder with a ..

..and rotating rod tests will be used to evaluate their motor function and compare it to a sham treated group and a levodopa treated group...

..with a broad spectrum of phenotype ranging from TH-deficient dopa-responsive dystonia (DRD) at the mild end to a levodopa-unresponsive infantile parkinsonism or progressive infantile encephalopathy phenotype at the severe end...

..and may underlie adaptive changes in basal ganglia circuits observed following prolonged treatment with levodopa (L-DOPA)...

..Animals will then receive either 1) oral motor therapy;2) oral motor therapy + levodopa;3) upper extremity therapy;4) upper extremity therapy + levodopa;5) levodopa therapy;or 6) no rehabilitation for ..

..be followed longitudinally by 18fluoro-methyl tyrosine PET imaging and a Clinical Rating Scale (CRS) off and on levodopa and apomorphine...

DESCRIPTION (provided by applicant): Levodopa induced dyskinesias (LID) are involuntary, abnormal movements that occur in most patients with Parkinson disease(PD) as a consequence of chronic use of the most effective symptomatic drug, ..

DESCRIPTION (provided by applicant): Levodopa therapy - the gold standard in Parkinson's disease (PD) treatment - causes disabling motor complications (dyskinesias) that are largely resistant to available drugs...

..DA enhancement therapy that targets cocaine use and cognitive deficits by combining two dopaminergic medications: levodopa and ropinirole...

PROJECT SUMMARY Dopamine (DA) therapy used for the treatment of Parkinson Disease (PD) consists of Levodopa and Dopamine receptor Agonist (DAA) medications...

..PD patients who take levodopa daily will undergo study procedures in the morning, within 3 hours of ingesting the medication...

..Treatments include pharmaceutical interventions such as levodopa and surgical procedures such as deep brain stimulation (DBS)...

..a wireless, ergonomic, and portable movement disorder technology designed for continuous monitoring of levodopa-induced dyskinesia (LID) and medication state in Parkinson's disease (PD)...

..Anti-cholinergic drugs, the only available drugs for PD before the development of levodopa treatment in the 1970s, remain to be in clinical use today...

..There is no cure and etiology is unknown. Medications such as levodopa provide good benefit for a number of years...

DESCRIPTION (provided by applicant): Despite the undeniable benefit of levodopa, symptomatic treatment for Parkinson's disease (PD) remains suboptimal...

..Dopamine replacement therapy with Levodopa (L-Dopa) is currently the standard pharmacotherapy for PD, but unfortunately, continued therapy with L-Dopa ..

..In the treatment of Parkinson's disease the drug levodopa increases dopamine release from the reduced number of dopaminergic neurons...

..blind, placebo controlled trial tested against the background of dopaminergic therapy (dopamine agonists and levodopa) and best PD care...

..g. bradykinesia, rigidity, and tremor, and show favorable response to levodopa (L-DOPA) or dopamine (DA) agonists...

..Project 1 addresses the serious clinical problem of levodopa-induced dyskinesias, which ultimately affect nearly all PD patients...

..wireless movement disorder system with continuous monitoring capabilities to detect and quantify the severity of levodopa-induced choreatic dyskinesias, or irregular rapid involuntary movements, in Parkinson's disease (PD)...

DESCRIPTION (provided by applicant): Synthonics is developing the metal-coordinated levodopa drug product, MCP-311, for FDA approval...

..disease progression, akinesia, start hesitation and FOG often becomes refractory to current treatments such as levodopa and deep brain stimulation. Currently there are no effective treatments for these symptoms...

..shown that the striatal levels of the chronic transcription factor (FosB consistently increase during chronic levodopa treatment...

..drugs in striatal injections or infusions to study the effects on striatal neurons and motor responses to levodopa. 3...

DESCRIPTION (provided by applicant): Levodopa (L-DOPA) remains the gold standard therapy for Parkinson's disease (PD) treatment, but it's long- term use is associated with disabling side effects consisting of uncontrolled ..

..All studies will test subjects with PD in the ON and OFF states to examine the effects of levodopa replacement on kinesthetic control of posture...

DESCRIPTION (provided by applicant): Response to carbidopa/levodopa (CD/LD), the most efficacious therapy in Parkinson's disease (PD), is often variable among patients...

..In addition, we will test the hypothesis that acute or chronic administration of levodopa or the dopamine agonist pramipexole may alter selected neuroimaging biomarkers...

..Now, more than 50 years after the discovery and use of levodopa for symptomatic treatment of Parkinsonian symptoms, we still do not have a disease-modifying drug for the ..

..release in TS by measuring striatal dopamine release in response to a cognitive task with and without exogenous levodopa. The proposal will exploit the newly developed Siemens PET-MRI scanner to acquire rCBF simultaneously with the ..

DESCRIPTION (provided by applicant): Our objective is to develop new drug treatments for the side effects of levodopa (L-DOPA) that occur in people with Parkinson's Disease...

..These mice develop an age-dependent progressive decrease in motor activity that is responsive to treatment with levodopa. At the level of pathology, the early and most robust phenotype is the axonopathy of the nigrostriatal ..

..synthesis of dopamine and avoid nausea and vomiting in patients with Parkinson's disease taking levodopa. The investigators reason that carbidopa could have a similar antiemetic effect in patients with FD...

..We will use similar methods to explore the role of central alpha2-adrenoreceptors in the orthostatic hypotension produced by levodopa therapy.

..as tremor-predominant PD (PDT) generally has better long-term motor outcome with fewer motor fluctuations, less levodopa-induced dyskinesias, a slower rate of progression, and fewer cognitive deficits when compared with akinetic-rigid-..

..Secondary analyses include individual components of the primary outcome measure, use of health services, levodopa-dose equivalents, safety, and tolerability...

..The goal of Project IV "Role of DA Receptors in Hypertension" is to determine whether levodopa can serve as a prodrug for DA and will reverse renal deterioration observed in hypertensive patients...

..Specifically, we will pursue the following aims: 1. To study the effects of DBS and levodopa administration on motor learning in PD...

..cerebral glucose metabolism and blood flow: blepharospasm, idiopathic torsion dystonia, Huntington's chorea and levodopa-induced dyskinesia...

..of several brain regions, but the excessive activation normalized after administration of the dopamine precursor levodopa. This drug is well suited for neuroimaging studies as it is well tolerated in TS and (when given with carbidopa) ..

..by applicant): Synthonics is interested in applying metal coordination chemistry to the dopamine precursor levodopa. This biochemical has served as the primary symptomatic pharmacotherapy for patients with Parkinson's ..

..b>levodopa, dopamine agonists)...

Parkinson's disease (PD) affects about 1 million people in North America. Medications, such as levodopa, and some surgical approaches are available for PD, but offer only symptomatic therapy...

..patients produces a similar subcortical and cortical pattern of activation as is seen following administration of levodopa. Global improvements in motor function and increased neural activity suggest forced-exercise may be altering ..

..In many patients, these "axial symptoms" are resistant to levodopa therapy...

..Compare the development and severity of dyskinesias in de novo parkinsonian monkeys treated chronically with (1) levodopa alone, or (2) a combination of levodopa and an NMDA antagonist. 4...

..to impaired repetitive movement in patients with PD and the effects of the two most successful treatments for PD, levodopa and high frequency stimulation of the subthalamic nucleus (STN-DBS), on these mechanisms...

..Patients with Parkinson's disease are treated with levodopa (L-DOPA), a precursor of dopamine. However, L-DOPA therapy has disabling side effects...

..tested on Parkinson's patients in the pilot experimental studies on measuring the effects of the levodopa treatment on motor fluctuations, and on detecting of the ipsilateral motor control impairment in patients with ..

..motor complications ("peak-dose" dyskinesia and "end of dose" failure) in MPTP parkinsonian monkeys treated with levodopa (L-dopa)...

..daily dose of Mucuna pruriens for 30 days prior to treatment with intermittant high doses of methyl ester of levodopa/benseraside to induce dyskinesias...

..Recently there has been interest in quantifying dyskinesia, a side effect of the levodopa that is used to reduce Parkinsonian symptoms, for the evaluation of pharmacological and surgical interventions ..

..abstract_text> ..

..All animals will be treated with levodopa to induce drug induced dyskinesias and periodically tested using a behavioral battery of tests (BBT) to assess ..

..the MPTP-treated Parkinsonian primate model: (i) evaluate clinical efficacy of AADC gene transfer combined with levodopa administration; (ii) evaluate the efficacy of AAV/AADC gene transfer aimed at alleviating levodopa-induced ..

..deprenyl and/or tocopherol administration to early, otherwise untreated PD patients will prolong the time until levodopa therapy is required to treat supervening disability...

..that these dyskinesias result from local "hot spots" of hyperdopaminergic function interacting with the levodopa primed brain...

..placebo-controlled, parallel-design multi-center clinical trial was developed to determine the impact, if any, of levodopa on the natural history of Parkinson's disease (PD)...

..Upon diagnosis, the primary form of intervention is the introduction of pharmacotherapy, primarily levodopa. However, in the early stages of PD, administration of levodopa is controversial...

DESCRIPTION (provided by applicant): Dopamine (DA) replacement in Parkinson's Disease (PD) via levodopa therapy lacks long term efficacy and results in debilitating side effects...

b>Levodopa (L-dopa) remains the most effective drug treatment for the symptomatic relief of Parkinson's disease...

This revised application proposes a pilot multicenter randomized placebo-controlled clinical trial of levodopa in children with ADHD both with and without periodic limb movements of sleep (PLMS) and restless legs syndrome (RLS)...

..that changes in NMDA receptor properties may be responsible for the development of the motor complications of levodopa therapy, such as wearing off and dyskinesias...