MedWorm: Carbidopa/Levodopa

  CARBIDOPA AND LEVODOPAtablet [Caremark L.L.C.]

Updated Date: Mar 17, 2010 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST))

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  Frequency-Velocity Mismatch: A Fundamental Abnormality in Parkinsonian Gait

In this study, foot movements of PD and normal subjects were monitored with an OPTOTRAK motion-detection system while they walked on a treadmill at different velocities. PD subjects were also paced with auditory stimuli at different frequencies. PD gait was characterized by step frequencies that were faster and stride lengths that were shorter than those of normal controls. At low walking velocities, PD stepping had a reduced or absent terminal toe lift, which truncated swing phases, producing shortened steps. Auditory pacing was not able to normalize step frequency at these lower velocities. Peak forward toe velocities increased with walking velocity and PD subjects could initiate appropriate foot dynamics during initial phases of the swing. They could not control the foot appropriately i...

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  Practice Parameter: Treatment of nonmotor symptoms of Parkinson disease: Report of the Quality Standards Subcommittee of the American Academy of Neurology

Objective: Nonmotor symptoms (sleep dysfunction, sensory symptoms, autonomic dysfunction, mood disorders, and cognitive abnormalities) in Parkinson disease (PD) are a major cause of morbidity, yet are often underrecognized. This evidence-based practice parameter evaluates treatment options for the nonmotor symptoms of PD. Articles pertaining to cognitive and mood dysfunction in PD, as well as treatment of sialorrhea with botulinum toxin, were previously reviewed as part of American Academy of Neurology practice parameters and were not included here. Methods: A literature search of MEDLINE, EMBASE, and Science Citation Index was performed to identify clinical trials in patients with nonmotor symptoms of PD published between 1966 and August 2008. Articles were classified according to a 4-tie...

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  Table of Contents

Escitalopram and Recovery of Cognition in Elderly Stroke PatientsCitalopram Shows Negative Effects in Patients With DRI and DepressionValproic Acid and AspirinLack of Sertraline Efficacy for Depression in AD PatientsAntipsychotic Prescribing Patterns and Outcomes for Delirium TreatmentImproved Cognition in AD Patients With SouvenaidCombination Donepezil and Intensive Cognitive RehabilitationNew Collaboration to Investigate GRNOPC1 for ADDuodenal Levodopa Infusion Improves Cognition in PD PatientNew Olanzapine WarningsNew Safety LabelingNew Approval (Source: The Brown University Geriatric Psychopharmacology Update)

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  Prescribing patterns of antiparkinsonian agents in Europe

In the 1990s, previous knowledge and randomized controlled trials supported the establishment of today's therapeutic recommendations in Parkinson's disease (PD). Scientific evidence allows different options for the treatment of PD. Patterns of use of antiparkinsonian agents (APA) across European countries may thus reflect these options. We wanted to describe patterns of use of APA in Europe and characterize the changes in prescription habits between 2003 and 2007. We investigated APA outpatient sales in 26 European countries where all commercially available APA were studied. Data for molecules and brand names were collected through IMS Health. Treatment per 1000 inhabitants daily (DID) was obtained from the WHO defined daily dose. Prescription pattern changes were evaluated by market share...

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  Effects of Carbidopa and Entacapone on the Metabolic Fate of the Norepinephrine Prodrug L-DOPS.

Conclusions: After L-DOPS administration plasma, NE levels do not increase sufficiently to increase blood pressure. Pressor responses to L-DOPS seem to reflect NE produced extraneuronally that escapes extensive enzymatic deamination and O-methylation and evokes vasoconstriction before reaching the systemic circulation. PMID: 20220040 [PubMed - as supplied by publisher] (Source: The Journal of Clinical Pharmacology)

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  Cerebral Infratentorial Large B-Cell Lymphoma Presenting as Parkinsonism.

Authors: Lin CM, Hong K Though rare, primary intracranial tumors can present with Parkinsonian symptoms, and diagnosis can be delayed unless there is a high index of suspicion. We herein present an 81-year-old man who was seen in our neurology clinic due to acute onset of unsteady gait and altered consciousness. Parkinsonism was initially diagnosed because of the typical manifestations. Levodopa was prescribed; however, there was a limited effect on his symptoms. Upon detail history and neurological examination, left sided hemiparesis was disclosed. Cerebral imaging studies revealed a solid mass over the right infratentorial para-midbrain area leading to reactive obstructive hydrocephalus. Work-up including chest and abdominal CT scanning, upper and lower GI endoscopy, and tumor marker...

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  Increased Melanoma Risk in Parkinson Disease: A Prospective Clinicopathological Study [Original Contribution]

Conclusions  Melanoma prevalence appears to be higher in patients with PD than in the general population. Despite difficulties in comparing other databases with this study population, the study supports increased melanoma screening in patients with PD. (Source: Archives of Neurology)

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  7. Cardiovascular reflex tests in autonomic nervous system evaluation in Parkinson’s disease and multiple system atrophy

The manifestations of dysautonomia in PD and MSA are broad and include gastrointestinal, urogenital, cardiovascular, sudomotor and thermoregulatory symptoms. The aim of our study was to evaluate the degree of dysautonomia in PD and MSA, as well as the usefulness of cardiovascular tests in differentiating parkinsonian syndromes. We evaluated 72 patients with PD and 19 with MSA, as well as 35 age-matched controls. The patients were divided in four groups (de novo patients – group I, patients with controllable PD without therapy complications – group II, patients with complications of levodopa treatment – group III, and MSA patients – group IV). Only orthostatic hypotension test showed statistical significance (p (Source: Clinical Neurophysiology)

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  PARCOPA (Carbidopa Levodopa) Tablet, Orally Disintegrating [Azur Pharma Inc.]

Updated Date: Mar 8, 2010 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST))

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  Neuropathy as a potential complication of levodopa use in Parkinson's disease: A Pharmacological and Pharmacovigilance point of view

No abstract. (Source: Movement Disorders)

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  Objective measurement of dyskinesia in Parkinson's disease using a force plate

Clinical investigation of levodopa-induced dyskinesia (LID) in Parkinson's disease (PD) is limited because of lack of objective measurements and no consensus on use of a standard measuring tool. Currently, clinical trials use subject-completed diaries of dyskinesia throughout the day or investigator-administered clinical rating scales. An objective and valid method of measuring LID would reduce bias, variability, and decrease the time and number needed in trials of potential anti-dyskinetic agents. We have investigated using a force plate under standing subjects, which records movement of the center of pressure (CoP) to quantify LID over a levodopa (L-dopa) cycle. Twenty-two PD subjects (15 with LID, 7 without LID) admitted to an inpatient research facility had their PD meds withheld overn...

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  Levodopa Deactivates Enzymes That Regulate Thiol−Disulfide Homeostasis and Promotes Neuronal Cell Death: Implications for Therapy of Parkinson’s Disease

Biochemistry, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). (Source: Biochemistry)

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  Long-term antidyskinetic efficacy of amantadine in Parkinson's disease

Several randomized placebo-controlled trials have consistently shown antidyskinetic effects of amantadine in levodopa treated patients with advanced Parkinson's disease (PD). However, all of these were of short duration and there have been claims that the effect of amantadine on levodopa induced dyskinesias (LID's) wear off after about 9 months of treatment. This randomized placebo-controlled parallel-group study was performed to assess the long-term antidyskinetic effect of amantadine in 32 PD patients, who after having been on stable amantadine therapy for LID over at least one year- were switched in a double blind manner to amantadine or placebo and followed for 3 weeks. Dyskinesia duration and intensity were assessed by UPDRS IV items 32 and 33 as well as by patient's diaries. The prim...

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  Leucine-Rich Repeat Kinase 2 Gene-Associated Disease: Redefining Genotype-Phenotype Correlation.

Conclusions: Such clinical and pathologic variability suggests Lrrk2 acts upstream from other proteins implicated in neurodegeneration. Specific mutations may be associated with alternative progressive supranuclear gaze palsy-like or 'pure' nigral degeneration phenotypes. A different effect on Lrrk2 kinase activity may play a role in such heterogeneity. PMID: 20197701 [PubMed - as supplied by publisher] (Source: Neuro-Degenerative Diseases)

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  Effects of subthalamic nucleus deep brain stimulation on sweating function in Parkinson's disease

Conclusions: These results, although based on a small sample, suggest that STN DBS, in addition to the effect to the mobility, might also favorably regulate sweat in idiopathic PD. (Source: Clinical Neurology and Neurosurgery)

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  Tyrosine hydroxylase deficiency in three Greek patients with a common ancestral mutation

We present the clinical, biochemical, and molecular findings of three Greek patients with tyrosine hydroxylase (TH) deficiency. All patients presented with a severe clinical phenotype characterized by prominent motor delay, infantile parkinsonism, oculogyric crises, and signs of autonomic dysfunction. Cerebrospinal fluid analysis disclosed reduced dopamine metabolites and normal pterins. Response to levodopa was favorable though not dramatic. All patients were homozygous for a previously reported mutation (p.L236P). SNP haplotype analysis was consistent with a common ancestral mutation, thus indicating a founder effect in Greek patients with TH deficiency. © 2010 Movement Disorder Society (Source: Movement Disorders)

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  Levodopa: Diphasic chorea: case report

(Source: Reactions)

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  Levodopa/carbidopa/sildenafil interaction: Interaction due to sildenafil abuse, leading to choreoathetosis in a patient with Parkinson's disease: case report

(Source: Reactions)

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  Dopamine Agonists Vie With l-Dopa for Parkinson's

MIAMI BEACH — Levodopa produces greater symptomatic relief for Parkinson's disease patients, compared with a dopamine agonist, consistent results of long-term studies indicate, but more dyskinesia and motor fluctuations are the trade-offs. (Source: Internal Medicine News)

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  Dopamine Agonists Quell Dyskinesia in PD

Major Findings: At 6 years, 50% of trial participants started on pramipexole and 69% started on levodopa experienced motor complications. (Source: Clinical Psychiatry News)

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  Sleep and Rhythm Consequences of a Genetically Induced Loss of Serotonin

Conclusion: In this unique genetic paradigm, the melatonin deficiency (caused by a lack of its substrate, serotonin) may cause the ultradian sleep-wake rhythm. Keywords: Sepiapterin reductase deficiency, hypersomnia, melatonin, ultradian sleep-wake rhythm, tetrahydrobiopterin, serotonin (Source: Sleep)

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  Eighteen month study of continuous intraduodenal levodopa infusion in patients with advanced Parkinson's disease: Impact on control of fluctuations and quality of life

Abstract: Symptom control, daily “on” time, and quality of life (QoL) of nine patients with Advanced Parkinson's Disease was assessed following 18-months treatment with Continuous Intraduodenal Levodopa Infusion (CIDLI). Patients had severe motor fluctuations and dyskinesias and had previously received treatment with oral levodopa and dopamine agonists. There were significant improvements in patients' symptoms on the Unified Parkinson's Disease Rating Scale, and QoL (Parkinson's Disease QoL Questionnaire; Schwab & England Capacity for Daily Living Scale; p  (Source: Parkinsonism and Related Disorders)

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  The effect of levodopa treatment on cerebral hemodynamics in patients with Parkinson's disease: Serial transcranial Doppler studies

This study included 17 patients with de novo PD. Homocysteine levels and TCD parameters at middle cerebral artery were investigated before and after 3 months of levodopa treatment. Correlation analyses were done between changes in homocysteine levels and TCD parameters. After 3 months of levodopa treatment, homocysteine level increased significantly from 13.3mg/dL to 17.0 mg/dL (p  (Source: Parkinsonism and Related Disorders)

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  Effective long-term subthalamic stimulation in PARK8 positive Parkinson’s disease

We report on a patient with advanced PD due to R793M missense mutation in the LRRK2 gene successfully treated by STN-DBS. Disease onset was at age 42 with bradykinesia, rigidity and rest tremor. During the course of the disease he developed severe motor fluctuations, dyskinesias, postural instability with falls, but preserved levodopa responsiveness. At age 60 the patient was treated by bilateral DBS of the STN. At one year after surgery a 66% improvement of the UPDRS motor score in the off-medication state was determined. During the long-term follow-up there was sustained benefit with 56% improvement of motor score after 8 years. Our report adds evidence that patients with LRRK2 monogenetic Parkinsonism are well suited candidates for DBS treatment and may indicate a potential g...

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  Pharmacologically Induced/Exacerbated Restless Legs Syndrome, Periodic Limb Movements of Sleep, and REM Behavior Disorder/REM Sleep Without Atonia: Literature Review, Qualitative Scoring, and Comparative Analysis

Conclusion: Based on scores ≥ 10 and trials of medication reduction/cessation, the strongest evidence available for drug induced RLS are for the following drugs: escitalopram; fluoxetine; L-dopa/carbidopa and pergolide; L-thyroxine; mianserin; mirtazapine; olanzapine; and tramadol. Since none of the PLMS articles assessed PLMI in trials of medication reduction/cessation, the strongest evidence based on scores ≥ 10 are for the following drugs: bupropion, citalopram, fluoxetine, paroxetine, sertraline, and venlafaxine. Based on scores ≥ 10 and/or trials of medication cessation, the strongest evidence for drug induced RBD/RSWA is for the following drugs: clomipramine, selegiline, and phenelzine. Keywords: Pharmacologically induced, periodic limb movements of sleep, rapid eye movemen...

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  Dopaminergic and non-dopaminergic pharmacological hypotheses for gait disorders in Parkinson's disease

Gait disorders form one component of the axial disorders observed in Parkinson's disease (PD). Indeed, short steps with a forward-leaning stance are diagnostic criteria for PD in the early stages of the condition. Gait disorders also represent a major source of therapeutic failure in the advanced stages of PD (with the appearance of freezing of gait and falls) because they do not respond optimally to the two hand late-stage therapeutics [ndash] levodopa and electrical subthalamic nucleus (STN) stimulation. The late onset of doparesistance in these disorders may be linked to propagation of neurodegeneration to structures directly involved in gait control and to non-dopaminergic neurotransmitter systems. The coeruleus locus (a source of noradrenaline) is rapidly and severely affected, leadin...

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  CARBIDOPA AND LEVODOPAtablet [UDL Laboratories, Inc.]

Updated Date: Feb 12, 2010 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST))

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  Reply: Neuropathy as a potential complication of levodopa use in Parkinson's disease: A pharmacological and pharmacovigilance point of view

No abstract. (Source: Movement Disorders)

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  Myopathy and parkinsonism in phosphoglycerate kinase deficiency

A 25-year-old man with exertional myoglobinuria had no evidence of hemolytic anemia, but he had severe parkinsonism that was responsive to levodopa. Phosphoglycerate kinase (PGK) activity was markedly decreased in muscle, and molecular analysis of the PGK1 gene identified the p.T378P mutation that was recently reported in a patient with isolated myopathy. This case reinforces the concept that PGK deficiency is a clinically heterogeneous disorder and raises the question of a relationship between PGK deficiency and idiopathic juvenile Parkinson disease. Muscle Nerve, 2010 (Source: Muscle and Nerve)

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  Comparative analysis of gait and speech in Parkinson's disease: hypokinetic or dysrhythmic disorders?

Gait and speech are automatic motor activities which are frequently impaired in Parkinson's disease. Obvious clinical similarities exist between these disorders but were never investigated. We propose to determine whether there exist any common features in Parkinson's disease between spatiotemporal gait disorders and temporal speech disorders. Gait and speech were analysed on 11 Parkinsonian patients (PP) undergoing deep-brain stimulation of the subthalamic nucleus (STN-DBS) and 11 control subjects under three conditions of velocity (natural, slow and speed). The patients were tested with and without l-dopa and stimulator ON or OFF. Locomotor parameters were recorded using an optoelectronic system. Speech parameters were recorded with a headphone while subjects were reading a short paragra...

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  Enhanced tolerability of the 5-hydroxytryptophane challenge test combined with granisetron

A recently developed oral serotonergic challenge test consisting of 5-Hydroxytryptophane (5-HTP, 200 mg) combined with carbidopa (CBD, 100 mg + 50 mg) exhibited dose-related neuroendocrine responsiveness and predictable pharmacokinetics. However, its applicability is limited by nausea and vomiting. A randomized, double-blind, placebo-controlled, four-way crossover trial was performed in 12 healthy male volunteers. The 5-HTP/CBD-challenge was combined with two oral anti-emetics (granisetron, 2 mg or domperidone, 10 mg) to investigate its reliability when side-effects are suppressed. The neuroendocrine response (serum cortisol and prolactin), the side-effect profile [Visual Analogue Scale Nausea (VAS)] and vomiting subjects per treatment were the main outcome measures. Compared to 5-HTP/CBD/...

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  Levodopa-aggravated lateral flexion of the neck and trunk as a delayed phenomenon of unilateral pallidotomy

No abstract. (Source: Movement Disorders)

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  SINEMET (Carbidopa And Levodopa) Tablet, Extended Release [Bristol-Myers Squibb Pharma Company]

Updated Date: Feb 2, 2010 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST))

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  Levodopa responsive hemidystonia associated with contralateral nigral lesion

Content Type Journal ArticleCategory Letter to the editorsDOI 10.1007/s00415-010-5466-yAuthors Chul Hyoung Lyoo, Yonsei University College of Medicine Department of Neurology, Gangnam Severance Hospital 712 Eonjuro, Gangnam-gu Seoul KoreaMyung Sik Lee, Yonsei University College of Medicine Department of Neurology, Gangnam Severance Hospital 712 Eonjuro, Gangnam-gu Seoul Korea Journal Journal of NeurologyOnline ISSN 1432-1459Print ISSN 0340-5354 (Source: Journal of Neurology)

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  Synosia Announces Positive Interim Results For Potential First-in-Class Treatment For Parkinson's Disease

Synosia Therapeutics announced interim positive data from a Phase IIa clinical study of an adenosine 2a (A2a) receptor antagonist (SYN115) in Parkinson's disease. The Phase IIa trial was a randomised, double-blind, placebo-controlled, cross-over study in 24 Parkinson's patients using doses up to 120mg/day for one week. The effects of SYN-115 as an add-on therapy to a stable dose of levodopa was assessed using a number of techniques, including functional Magnetic Resonance Imaging (fMRI), clinical ratings such as the Unified Parkinson's Disease Rating Scale and various cognitive tests... (Source: Health News from Medical News Today)

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  Current concepts in the management of Parkinson disease.

Authors: Hayes MW, Fung VS, Kimber TE, O'Sullivan JD Parkinson disease (PD) is a multisystem neurodegenerative disorder that affects about 1% of the population over the age of 55 years and has mean age of onset of about 60 years. The Braak hypothesis proposes that the earliest pathological evidence of PD is found in the enteric nervous system, medulla and olfactory bulb, and only subsequently progresses (over years) to the substantia nigra and cortex. Non-motor symptoms, such as constipation, hyposmia and sleep disorders, may precede typical motor features of PD by several years. No treatment has been convincingly shown to slow PD progression (ie, a neuroprotective drug remains elusive). Symptomatic benefit from dopaminergic therapy is usually maintained throughout the course of the di...

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  [Different faces of levodopa-responsive dystonia.]

Authors: Losada-Lopez M, Lopez-Garre P, Garcia-Ruiz PJ PMID: 20146193 [PubMed - in process] (Source: Revista de Neurologia)

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  [Homocysteine and cognitive impairment in Parkinson's disease.]

CONCLUSIONS. Our study confirms presence of high levels of Hc in PD patients under treatment with levodopa, more evident in patients with cognitive impairment. PMID: 20146187 [PubMed - in process] (Source: Revista de Neurologia)

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  Effect of l-Dopa on metabotropic glutamate receptor 5 in the brain of parkinsonian monkeys

This study investigated mGluR5 changes in MPTP lesioned monkeys. The effect of a chronic 1 month treatment with l-Dopa on mGluR5-specific binding and mRNA levels was investigated in MPTP monkeys killed 4 or 24 h after their last l-Dopa administration. [3H]ABP688 specific binding in the putamen was elevated in l-Dopa-treated MPTP monkeys killed 24 h but not 4 h after their last l-Dopa dose compared with vehicle-treated MPTP monkeys. Caudate nucleus [3H]ABP688-specific binding was elevated in both groups of l-Dopa treated compared with vehicle[ndash]treated MPTP monkeys. In contrast, caudate nucleus and putamen mGluR5 mRNA levels were elevated only in l-Dopa-treated MPTP monkeys killed 4 h after their last l-Dopa administration. MPTP monkeys killed 4 h after their last l-Dopa treatment showe...

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  A Pilot Study of levodopa as treatment for residual amblyopia in children 8 to 17 years old

Purpose: To report the results of a randomized pilot study of levodopa therapy for residual amblyopia in older children. Patients and Methods: Thirty-three subjects 8 to 17 years of age (mean, 11.1 years) with residual amblyopia 20/50 to 20/400 (mean 20/80−2) following treatment with at least 2 hours of daily patching and no improvement over at least 4 weeks. Study intervention consisted of 2 hours of daily patching plus randomization to either 0.51 mg/kg/tid levodopa with carbidopa 0.17 mg/kg/tid OR 0.76 mg/kg/tid levodopa with carbidopa 0.17 mg/kg/tid for 8 to 10 weeks. Visual acuity was measured with E-ETDRS testing after stopping the medication and again 8-12 weeks later after a period of patching alone. Adverse events were elicited at each contact. (Source: Journal of AAPOS)

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  Levodopa/carbidopa: Serpentine tongue: case report

(Source: Reactions)

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  CARBIDOPA AND LEVODOPAtablet [Sun Pharmaceutical Industries Limited]

Updated Date: Jan 27, 2010 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST))

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  Camptocormia in idiopathic Parkinson's disease: A focal myopathy of the paravertebral muscles

The objective of our study was to describe the clinical features of camptocormia, an involuntary, marked flexion of the thoracolumbar spine in idiopathic Parkinson's disease (PD) and to understand its etiology. In a prospective, cross-sectional study, we examined 15 patients with PD and camptocormia using laboratory parameters, EMG, muscle magnetic resonance imaging, and biopsy of the paravertebral muscles. The clinical data were compared with a matched control group of PD patients without camptocormia, and the biopsies were compared with muscles from age-matched autopsies. Almost all the patients (median age, 68.0 years; 7 women) with camptocormia suffered from advanced PD. Camptocormia occurred at a median of 9.0 years after the PD diagnosis. Compared with our clinical control group, bac...

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  GCH1 mutation and clinical study of Chinese patients with dopa-responsive dystonia

Dopa-responsive dystonia (DRD) is typically caused by heterozygous mutations in GTP cyclohydrolase 1 gene (GCH1). Our aim was to investigate the clinical and genetic features of Chinese DRD patients. We analyzed a cohort of Chinese DRD patients' clinical data. Mutation of the GCH1 gene was screened by direct sequencing. Additionally, multiplex ligation-dependent probe amplification (MLPA) assay targeting the GCH1 and the TH gene to evaluate large exon deletion or duplicate mutation of the genes were performed in point mutation-negative patients. Ten sporadic DRD patients and two pedigrees including six patients were included in the study. The onset age ranged from 3 to 15 years old. All patients initially presented with walking problems due to lower limb dystonia. The delay between onset a...

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  Pramipexole combined with levodopa improves motor function but reduces dyskinesia in MPTP-treated common marmosets

Reduced expression of dyskinesia is observed in levodopa-primed MPTP-treated common marmosets when dopamine agonists are used to replace levodopa. We now investigate whether a combination of the D-2/D-3 agonist pramipexole and levodopa also reduces dyskinesia intensity while maintaining the reversal of motor disability. Drug naïve, non-dyskinetic MPTP-treated common marmosets were treated daily for up to 62 days with levodopa (12.5 mg/kg plus carbidopa 12.5 mg/kg p.o. BID) or pramipexole (0.04-0.3 mg/kg BID) producing equivalent reversal of motor disability and increases in locomotor activity. Levodopa alone resulted in marked dyskinesia induction but little or no dyskinesia resulted from the administration of pramipexole. From day 36, some animals were treated with a combination of levod...

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  Impact of dendritic spine preservation in medium spiny neurons on dopamine graft efficacy and the expression of dyskinesias in parkinsonian rats

Dopamine deficiency associated with Parkinson's disease (PD) results in numerous changes in striatal transmitter function and neuron morphology. Specifically, there is marked atrophy of dendrites and dendritic spines on striatal medium spiny neurons (MSN), primary targets of inputs from nigral dopamine and cortical glutamate neurons, in advanced PD and rodent models of severe dopamine depletion. Dendritic spine loss occurs via dysregulation of intraspine Cav1.3 L-type Ca2+channels and can be prevented, in animal models, by administration of the calcium channel antagonist, nimodipine. The impact of MSN dendritic spine loss in the parkinsonian striatum on dopamine neuron graft therapy remains unexamined. Using unilaterally parkinsonian Sprague[ndash]Dawley rats, we tested the hypothesis that...

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  Oral and Infusion Levodopa-Based Strategies for Managing Motor Complications in Patients with Parkinsons Disease

(Source: CNS Drugs)

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  Tolerability and Safety of Ropinirole versus Other Dopamine Agonists and Levodopa in the Treatment of Parkinsons Disease: Meta-Analysis of Randomized Controlled Trials

(Source: Drug Safety)

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  Cochrane review: Monoamine oxidase B inhibitors versus other dopaminergic agents in early Parkinson's disease

Source: Cochrane Library Area: Evidence > Drug Class Focused Reviews Background It has been postulated that monoamine oxidase B (MAO-B) inhibitors alter disease progression in Parkinson's disease (PD) but trials have produced conflicting results.   Objectives To assess the effectiveness and safety of long-term use of MAO-B inhibitors compared with other dopaminergic agents in early PD.   Search strategy We searched several electronic databases including: the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2009), MEDLINE (January 1950 to February 2009) and EMBASE (January 1980 to February 2009). We also handsearched neurology and movement disorders conference proceedings, checked reference lists of relevant studies and contacted other resea...

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  [Reflection and Reaction] Imaging for early differential diagnosis of parkinsonism

Clinical diagnosis of Parkinson's disease relies on the presence of characteristic motor symptoms, such as bradykinesia, rigidity, and resting tremor, and non-motor features are increasingly being recognised as early symptoms. Nonetheless, early differential diagnosis can be difficult, especially because essential tremor, vascular parkinsonism, drug-induced parkinsonism, and atypical parkinsonian syndrome (ie, multiple system atrophy and progressive supranuclear palsy) might initially present with overlapping clinical features. Good response to dopaminergic drugs, particularly levodopa, is often used to support the clinical diagnosis of Parkinson's disease. However, some patients with pathologically confirmed Parkinson's disease have a poor response to levodopa; conversely, some patients w...

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  MK-801 inhibits l-DOPA-induced abnormal involuntary movements only at doses that worsen parkinsonism.

Authors: Paquette MA, Anderson AM, Lewis JR, Meshul CK, Johnson SW, Paul Berger S Amantadine and dextromethorphan suppress levodopa (l-DOPA)-induced dyskinesia in Parkinson's disease patients and abnormal involuntary movements (AIM) in the 6-hydroxydopamine (6-OHDA) rat model. These medications have been hypothesized to exert their therapeutic effects by a noncompetitive N-methyl-d-aspartate (NMDA) antagonist mechanism, but they also have known serotonin (5-HT) indirect agonist effects that could suppress AIM. This raised the possibility that NMDA antagonists lacking 5-HTergic effects would not have the anti-dyskinetic action predicted by previous investigators. To test this hypothesis, we investigated MK-801, the most widely-studied NMDA antagonist. We found that chronic low-dose MK-8...

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  Differentiating vascular parkinsonism from idiopathic Parkinson's disease: A systematic review

Vascular parkinsonism (VP) remains a loose constellation of various clinical features. We systematically reviewed studies comparing clinical, neuroimaging and other investigations that might distinguish VP from idiopathic Parkinson's disease (PD). Medline, Embase, Cinahl (R), and PsycINFO were searched by querying appropriate key words. Reports were included if the study population contained comparative findings between patients with VP and PD. Twenty-five articles fulfilled the selection criteria. Patients with VP were older, with a shorter duration of illness, presented with symmetrical gait difficulties, were less responsive to levodopa, and were more prone to postural instability, falls, and dementia. Pyramidal signs, pseudobulbar palsy, and incontinence were more common in VP. Tremor ...

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  The effect of peripheral enzyme inhibitors on levodopa concentrations in blood and CSF

Levodopa combined with a dopa-decarboxylase inhibitor, such as carbidopa, shifts the metabolism to the COMT pathway. Adding the peripheral acting COMT inhibitor entacapone provides improvement for patients with PD suffering from motor fluctuations. We studied the effects of the enzyme inhibitors entacapone and carbidopa on the levodopa concentrations in CSF and in blood. Five PD patients with wearing-off underwent lumbar drainage and intravenous microdialysis. Samples were taken 12 h daily for 3 days. Day 1; intravenous levodopa was given, day 2; additional oral entacapone 200 mg tid, day 3; additional oral entacapone 200 mg tid and carbidopa 25 mg bid. Levodopa in CSF and in dialysates was analysed. The AUC for levodopa increased both in blood and CSF when additional entacapone was given ...

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  Genitourinary dysfunction in Parkinson's disease

Bladder dysfunction (urinary urgency/frequency) and sexual dysfunction (erectile dysfunction) are common nonmotor disorders in Parkinson's disease (PD). In contrast to motor disorders, genitourinary autonomic dysfunctions are often nonresponsive to levodopa treatment. The brain pathology causing the bladder dysfunction (appearance of overactivity) involves an altered dopamine-basal ganglia circuit, which normally suppresses the micturition reflex. By contrast, hypothalamic dysfunction is mostly responsible for the sexual dysfunction (decrease in libido and erection) in PD, via altered dopamine-oxytocin pathways, which normally promote libido and erection. The pathophysiology of the genitourinary dysfunction in PD differs from that in multiple system atrophy; therefore, it might aid in diff...

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  Levodopa-Induced Dyskinesias in Spinocerebellar Ataxia Type 2 [Images in Neurology]

(Source: Archives of Neurology)

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  Effects of a Dopamine Agonist on the Pharmacodynamics of Levodopa in Parkinson Disease [Clinical Trials]

Conclusions  Pramipexole augmented the motor response to levodopa beyond a simple additive effect and increased the severity of levodopa-induced dyskinesia. When considering a combination of these therapies, an appropriate balance should be maintained regarding gain of motor function vs worsening of dyskinesia. Trial Registration  clinicaltrials.gov Identifier: NCT00666653 (Source: Archives of Neurology)

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  Dopamine Agonist Withdrawal Syndrome in Parkinson Disease [Original Contribution]

Conclusions  Dopamine agonists have a stereotyped withdrawal syndrome that can lead to profound disability in a subset of patients. Physicians should monitor patients closely when tapering these medications. (Source: Archives of Neurology)

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  Skin cancer and Parkinson's disease

The report of an increased frequency of melanoma during the clinical development of rasagiline prompted a renewed interest in a possible association between skin cancer and Parkinson's disease (PD). The evaluation of this risk ended in a recommendation to perform a periodic dermatological examination as a follow-up measure of their treatment. The recognition of this safety concern lead to the need to clarify if the risk of skin cancer is indeed associated with PD and if levodopa or other anti-parkinsonian drugs might contribute to increase such risk. To answer these questions, we critically reviewed all clinical studies available concerning the association between skin cancer and PD. We found 26 studies on cancer occurrence in PD. The best data available suggest the risk of cancer is reduc...

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  Agonist-like pharmacotherapy for stimulant dependence: preclinical, human laboratory, and clinical studies

This report reviews preclinical, human laboratory, and clinical trial data supporting the agonist-like approach, including risks and benefits. Future directions for development of agonist-like medications are also discussed. (Source: Annals of the New York Academy of Sciences)

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  Striatal inhibition of PKA prevents levodopa-induced behavioural and molecular changes in the hemiparkinsonian rat.

Authors: Lebel M, Chagniel L, Bureau G, Cyr M L-3,4-dihydroxyphenylalanine methyl ester hydrochloride (L-DOPA) is the gold standard for symptomatic treatment of Parkinson's disease (PD), but long-term therapy is associated with the emergence of abnormal involuntary movements (AIMS) known as L-DOPA-induced dyskinesias (LID). The molecular changes underlying LID are not completely understood. Using the 6-hydroxydopamine-lesioned rat model of PD, we showed that L-DOPA elicits profound alterations in the activity of 3 LID molecular markers, namely DeltaFosB, DARPP-32 and extracellular signal-regulated kinases 1 and 2 (ERK1/2), as well as in phosphorylation levels of the cytoskeletal-associated protein tau. These modifications are triggered by protein kinase A (PKA) activation and intermitt...

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  Hyperhomocysteinemia Due to Levodopa Treatment as a Risk Factor for Osteoporosis in Patients with Parkinson’s Disease

In conclusion, these findings indicate that hyperhomocysteinemia due to levodopa intake may be one additional risk factor for osteoporosis and fracture in PD patients. Reducing Hcy may be a therapeutic modality for treating osteoporosis in PD patients taking levodopa. Content Type Journal ArticleDOI 10.1007/s00223-009-9327-6Authors Seung Hun Lee, University of Ulsan College of Medicine Division of Endocrinology and Metabolism, Asan Medical Center 388-1 Poongnap 2-Dong, Songpa-Gu Seoul 138-736 Republic of KoreaMi Jung Kim, University of Ulsan College of Medicine Parkinson/Alzheimer Center, Department of Neurology, Asan Medical Center Seoul 138-736 Republic of KoreaBeom-Jun Kim, University of Ulsan College of Medicine Division of Endocrinology and Metabolism, Asan Medical Center 388-1...

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  Effects of pedunculopontine nucleus area stimulation on gait disorders in Parkinson's disease

Gait disturbances are frequent and disabling in advanced Parkinson's disease. These symptoms respond poorly to usual medical and surgical treatments but were reported to be improved by stimulation of the pedunculopontine nucleus. We studied the effects of stimulating the pedunculopontine nucleus area in six patients with severe freezing of gait, unresponsive to levodopa and subthalamic nucleus stimulation. Electrodes were implanted bilaterally in the pedunculopontine nucleus area. Electrode placement was checked by postoperative magnetic resonance imaging. The primary outcome measures were a composite gait score, freezing of gait questionnaire score and duration of freezing episodes occurring during a walking protocol at baseline and one-year follow-up. A double-blind cross-over study was ...

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  CARBIDOPA AND LEVODOPAtablet, Extended Release [SUN PHARMACEUTICAL INDUSTRIES LIMITED]

Updated Date: Jan 4, 2010 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST))

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  Istradefylline as monotherapy for Parkinson disease: Results of the 6002-US-051 trial

Conclusions: Istradefylline, as monotherapy in patients with PD, is safe and well tolerated. However, efficacy in improving motor symptoms in early PD was not statistically demonstrated by this study. (Source: Parkinsonism and Related Disorders)

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  Neuropsychiatric behaviors in the MPTP marmoset model of Parkinson's disease.

CONCLUSIONS: The data suggest that neuropsychiatric disorders in PD are more likely an interaction between levodopa and the disease state than a consequence of sensitisation to repeated dopaminergic therapy. PMID: 20169779 [PubMed - in process] (Source: The Canadian Journal of Neurological Sciences)

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  Hyperhomocysteinemia recurrence in levodopa-treated Parkinson's disease patients

Conclusions: One-month intake of 5 mg/day folate normalizes plasma tHcy levels in all hyper-homocysteinemic PD patients. Following folate discontinuation, hyper-tHcy recurs in all patients within 4 months. Knowledge of this time interval is useful to optimize pulses of folate therapy in hyper-homocysteinemic patients with PD. (Source: European Journal of Neurology)

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  Metabotropic glutamate receptor type 5 in levodopa-induced motor complications.

Authors: Ouattara B, Grégoire L, Morissette M, Gasparini F, Vranesic I, Bilbe G, Johns DR, Rajput A, Hornykiewicz O, Rajput AH, Gomez-Mancilla B, Di Paolo T Metabotropic glutamate receptors type 5 (mGluR5) are implicated in regulation of synaptic plasticity and learning, and were the focus of our investigation in human Parkinson's disease (PD) patients with dyskinesias and wearing-off, and in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) monkeys with dyskinesias. Using the selective mGluR5 ligand [(3)H]ABP688 autoradiography, we measured mGluR5 in brain slices from 11 normal and 14 PD patients and from MPTP monkeys, in relation to motor complications (dyskinesias and wearing-off) associated with treatment with l-dopa. In 16 monkeys with a bilateral MPTP lesion and four contr...

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  CARBIDOPA AND LEVODOPAtablet [McKesson Packaging Services Business Unit Of McKesson Corporation]

Updated Date: Dec 22, 2009 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST))

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  CARBIDOPA AND LEVODOPAtablet [TEVA Pharmaceuticals USA Inc]

Updated Date: Dec 22, 2009 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST))

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  Teva launches generic co-beneldopa (levodopa/benserazide)

Source: PharmaLive Area: News Teva UK Limited has launched co-beneldopa capsules, a generic version of Madopar® (Roche).  It is indicated for treatment of symptoms of Parkinson's disease and is available in the Teva 360 livery in the following strengths:   . Co-Beneldopa capsules 50 mg / 12.5 mg x 100 (£5.36) . Co-Beneldopa capsules 100 mg / 25 mg x 100 (£7.47) . Co-Beneldopa capsules 200 mg / 50 mg x 100 (£12.74)   (Prices from Teva price list December 2009) (Source: NeLM - News)

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  Large differences in levodopa dose requirement in Parkinson's disease: men use higher doses than women

Conclusions: We conclude that the levodopa requirement in PD ranges considerably, and that men use higher levodopa dose than women. Levodopa requirement is constant during the progression of the disease in low-dose patients but increases in high-dose patients. (Source: European Journal of Neurology)

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  Reprogramming guided by the fused images of MRI and CT in subthalamic nucleus stimulation in Parkinson disease

Conclusions: CT-MR fusion images helped to reprogram stimulation parameters with ease and confidence in a time-saving manner and resulted in further clinical improvement. This method could complement the conventional method of adjusting stimulation parameters after bilateral STN-DBS. (Source: Clinical Neurology and Neurosurgery)

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  Direct switch from levodopa/benserazide or levodopa/carbidopa to levodopa/carbidopa/entacapone in Parkinson’s disease patients with wearing-off: efficacy, safety and feasibility—an open-label, 6-week study

Abstract  The study objective was to assess the efficacy, safety and feasibility of switching from levodopa/benserazide (LB) or levodopa/carbidopa (LC) to levodopa/carbidopa/entacapone (LCE) in Parkinson’s disease (PD) patients with wearing-off. This was a multicenter, open-label, 6-week study; the primary outcome was success rate based on the patient-assessed Clinical Global Impression of Change (P-CGI-C). Secondary outcomes included investigator-assessed CGI-C (I-CGI-C), change from baseline in Unified Parkinson’s Disease Rating Scale (UPDRS), motor/non-motor wearing-off symptoms and quality of life–visual analog scale (QoL-VAS). After switching to LCE, 77% of patients reported an ‘improvement’ (p < 0.0001 vs. patients reporting ‘no change or worse...

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  Urate as a Predictor of the Rate of Clinical Decline in Parkinson Disease [Original Contribution]

Conclusions  Higher serum and cerebrospinal fluid urate concentrations at baseline were associated with slower rates of clinical decline. The findings strengthen the link between urate concentration and PD and the rationale for considering central nervous system urate concentration elevation as a potential strategy to slow PD progression. Published online October 12, 2009 (doi:10.1001/archneurol.2009.247). (Source: Archives of Neurology)

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  Motor Phenotype of LRRK2 G2019S Carriers in Early-Onset Parkinson Disease [Original Contribution]

Conclusion  Early-onset Parkinson disease G2019S LRRK2 carriers are more likely to manifest the PIGD phenotype, which may have implications for disease course. (Source: Archives of Neurology)

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  Short- and long-term dopaminergic effects on dysarthria in early Parkinson’s disease

Abstract  While the beneficial effect of levodopa on motor impairment in Parkinson’s disease (PD) has been well documented, its effect on speech has rarely been examined and the respective literature is inconclusive. The aim of our study was to analyze the effect of short-term levodopa admission and long-term dopaminergic treatment on speech in PD patients in early stages of the disease. Motor examination according to UPDRS III and speech testing were performed in 23 PD patients (9 males; median age 68, 42–78 years) in the early morning after having abstained from dopaminergic medication overnight (“off” state, t0) after administration of 200 mg of soluble levodopa (t1), and at follow-up after 12–14 weeks under stable dopaminergic medication (t2). S...

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  Gene Therapy Well Tolerated in Parkinson's Patients

In patients with Parkinson's disease, infusion of an adenovirus vector containing the gene for L-amino acid decarboxylase (AADC) -- the enzyme that converts levodopa to dopamine -- boosts availability of the enzyme and leads to improvement, according to phase I trial results published in the November 17th issue of Neurology. Reuters Health Information (Source: Medscape Today Headlines)

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  NMDA antagonist memantine improves levodopa-induced dyskinesias and "On-off" phenomena in Parkinson's disease

No Abstract. (Source: Movement Disorders)

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  BDNF levels are not related with levodopa-induced dyskinesias in MPTP monkeys

Levodopa-induced dyskinesias (LIDs) are frequent in parkinsonian patients and may result from an aberrant plasticity. Brain-derived neurotrophic factor (BDNF) represents a likely candidate to subserve neuroadaptive processes encountered in LIDs. We compared striatal BDNF levels measured by ELISA in levodopa-treated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) monkeys having developed LIDs compared with animals where LIDs were prevented by the addition of CI-1041 (NR1A/2B NMDA receptor antagonist) or low doses of cabergoline (dopamine D2 receptor agonist). We observed reduced striatal BDNF concentrations in levodopa-treated MPTP monkeys with or without LIDs, suggesting that levodopa treatment is associated with reduced striatal BDNF levels and is independent of dyskinesias. © 2009 M...

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  PET Studies of Cerebral Levodopa Metabolism: A Review of Clinical Findings and Modeling Approaches

[18F]Fluoro-3,4-dihydroxyphenyl-L-alanine (FDOPA) was one of the first successful tracers for molecular imaging by positron emission tomography (PET), and has proven immensely valuable for studies of Parkinson’s disease. Following intravenous FDOPA injection, the decarboxylated metabolite [18F] fluorodopamine is formed and trapped within terminals of the nigrostriatal dopamine neurons; reduction in the simple ratio between striatum and cerebellum is indicative of nigrostriatal degeneration. However, the kinetic analysis of dynamic FDOPA-PET recordings is formidably complex due to the entry into brain of the plasma metabolite O-methyl-FDOPA and due to the eventual washout of decarboxylated metabolites. Linear graphical analysis relative to a reference tissue input function is popular ...

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  Drug Candidates In Pipeline Offer Potential For Parkinson's Disease Therapeutics Market, Says Frost & Sullivan

The Parkinson's disease therapeutics market in 2008 amounted to over $1B in the European Union (EU), which includes total sales of carbidopa/levodopa, dopamine agonists, MAO-B inhibitors, COMT inhibitors and anticholinergics used for disease symptom relief. (Source: Pharmaceutical Online News)

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  SMC accepts pramipexole (MirapexinT) for Parkinson's disease

Source: Scottish Medicines Consortium (SMC) Area: Evidence > Drug Specific Reviews Following an abbreviated submission, the Scottish Medicines Consortium (SMC) has accepted pramipexole dihydrochloride monohydrate prolonged release tablets (MirapexinT) for use within NHS Scotland for the treatment of the signs and symptoms of idiopathic Parkinson's disease, alone (without levodopa) or in combination with levodopa, i.e. over the course of the disease, through to late stages when the effect of levodopa wears off or becomes inconsistent and fluctuations of the therapeutic effect occur (end of dose or "on off" fluctuations).   The drug advice notes that in patients for whom the use of pramipexole is appropriate, the prolonged-release formulation can provide the same daily dose as exis...

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  Compulsive habits in restless legs syndrome patients under dopaminergic treatment

Abstract: Since the introduction of levodopa therapy and dopaminergic replacement therapy to abate symptoms of idiopathic Parkinson's disease, repetitive compulsive behaviors have been reported and are now considered to be drug-related response complications. As dopamine (DA) agonists are the licensed treatment in Restless Legs Syndrome (RLS), a survey was conducted to determine the extent to which patients with RLS present compulsive behaviors. The aim of this study was to investigate the relationship between DA agonists and the occurrence of motor or behavioral compulsions, stress, depression, and sleep disturbance in RLS patients. A questionnaire was mailed three times, at four-month intervals over a period of 8months to all patients of the Quebec Memory and Motor Skills Disorders Clini...

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  Oxidative damage in Parkinson disease. Measurement using accurate biomarkers.

Authors: Seet RC, Lee CY, Lim EC, Tan JJ, Quek AM, Chong WL, Looi WF, Huang SH, Wang H, Chan YH, Halliwell B Oxidative damage has been implicated in the pathogenesis of Parkinson disease (PD) but literature data are confusing. Using products of lipid and DNA oxidation measured by accurate methods, we assessed the extent of oxidative damage in PD patients. The levels of plasma F(2)-isoprostanes (F(2)-IsoPs), hydroxyeicosatetraenoic acid products (HETEs), cholesterol oxidation products (COPs), neuroprostanes (F(4)-NPs), phospholipase A(2) (PLA(2)) and platelet activating factor-acetylhydrolase (PAF-AH) activities, urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and serum high-sensitivity C-reactive protein (hs-CRP) were compared in 61 PD patients and 61 age-matched controls. The levels of p...

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  Spatial distribution of Parkinson's disease mortality in Spain, 1989-1998, as a guide for focused aetiological research or health-care intervention.

Conclusions: Municipal PD mortality in Spain was unevenly distributed. Patterns were roughly similar to reported provincial PD mortality and use of levodopa. While the overall pattern appears to result from spatially selective PD undiagnosis, and can not be ascribed to industrial emissions, it can not be excluded that selected "hot spots" reflect genetic factors and/or environmental exposures inducing parkinsonism. A few municipal populations, located in low-mortality-risk areas in the vicinity of polluting plants or registering high excess PD mortality, might constitute a priority for conducting direct etiological studies. Additionally, interventions aimed to reduce potential PD undiagnosis might be most appropriate in the South. (Source: BMC Public Health - Latest articles)

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  RADAR review: Pramipexole (Sifrol®) for early Parkinson's disease

Source: National Prescribing Service Area: News A RADAR (Rational Assessment of Drugs and Research) review on pramipexole (Sifrol®) for early Parkinson's disease has been published and is available via the link below. This review was completed on behalf of the National Prescribing Service (NPS), which is an independent Australian organisation supporting the quality use of medicines.   The authors highlight the following summary points (taken directly from the source):   . Pramipexole is a non-ergot dopamine agonist for treating the symptoms of Parkinson's disease. . Using pramipexole instead of levodopa as initial therapy for early Parkinson's disease delays the development of motor complications (wearing off, dyskinesias or on-off fluctuations). . Pramip...

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  A New Mixture Design-Based Approach to Graphical Screening of Potential Interconnections and Variability Processes in Metabolic Systems

This article presents a new metabolomic approach helping to graphically analyse the flexibility of metabolic regulation systems. Its principle consists in extracting a metabolic backbone from iterative combinations of metabolic profiles representing different metabolic trends. The iterated combinations were performed on the basis of Scheffe matrix then averaged to calculate a response matrix of smoothed metabolic profiles. From such a smoothed matrix, a graphical analysis of relationships between metabolites highlighted different scale-dependent variation paths responsible for the observed metabolic trends. Such a flexibility favouring some metabolites at the expense of others was indirectly checked by a single kinetic approach by considering both the variation of maximal concentrations an...

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  Anxious and depressive symptoms in Parkinson's disease: The French cross-sectionnal DoPaMiP study

Anxiety has been less extensively studied than depression in Parkinson's disease (PD). The DoPaMiP survey allowed assessing simultaneously anxiety and depressive symptoms in PD and comparing correlations of both symptoms with clinical and therapeutic features of the disease. Cross sectional survey conducted prospectively in 450 ambulatory nondemented PD patients and 98 patients with other disorders than PD. Anxiety and depressive symptoms were assessed using the Hospital Anxiety and Depression Scale (HADS), parkinsonism using the Unified Parkinson's Disease Rating Scale (UPDRS). Other clinical factors were measured using a structured standardized examination/questionnaire. The mean HADS-A (anxiety) subscore was higher in PD patients than in the others (8.2 ± 3.9 vs. 6.5 ± 3.2, P < 10-4) ...

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  Health related quality of life in early Parkinson's disease: Impact of motor and non-motor symptoms, results from Chinese levodopa exposed cohort

Conclusions: In our sample patients with levodopa therapy, motor disability and severity of parkinsonism contributed to a lesser extent to patients’ self-report distress, within the first 5 years of disease onset. The clinical factors that showed the highest predictive value for worsen HR-QOL were non-motor symptoms, such as depression, sleep disorders, and fatigue. Great effort should be made to recognize and treat those conditions, thus improving all aspects of PD and giving these patients as a good HR-QOL as possible. (Source: Parkinsonism and Related Disorders)

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  Parkin and PINK1 parkinsonism may represent nigral mitochondrial cytopathies distinct from Lewy body Parkinson's disease

Abstract: Recent authors have concluded that Parkinson's disease (PD) is too heterogeneous to still be considered a single discrete disorder. They advise broadening the concept of PD to include genetic parkinsonisms, and discard Lewy pathology as the confirmatory biomarker. However, PD seen in the clinic is more homogeneous than often recognized if viewed from a long-term perspective. With appropriate diagnostic criteria, it is consistently associated with Lewy neuropathology, which should remain the gold standard for PD diagnostic confirmation. PD seen in the clinic has an inexorable course with eventual development of not only levodopa-refractory motor symptoms, but often cognitive dysfunction and prominent dysautonomia. This contrasts with homozygous parkin, PINK1 or DJ1 parkinsonism, c...

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  Systematic review of apomorphine infusion, levodopa infusion and deep brain stimulation in advanced Parkinson's disease

Abstract: The effectiveness of oral levodopa in complex Parkinson's disease (PD) is limited by its short half-life, and the resulting pulsatile dopaminergic stimulation leads to complex motor fluctuations and dyskinesia.Several treatments provide more continuous/less pulsatile dopaminergic stimulation by modifying the pharmacokinetics of levodopa or dopamine; however, patients with advanced disease can be refractory to these treatments. In such cases infusion therapies (apomorphine and intraduodenal levodopa) and neurosurgery (deep brain stimulation [DBS]) may be used. The purpose of this systematic review is to assess, as far as possible, the relative effectiveness of these therapies.There were no randomised controlled trials comparing the three treatment modalities or any directly compar...

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  Caffeic acid improves the bioavailability of l-dopa in rabbit plasma

In conclusion, caffeic acid at a dose of 10 mg·kg-1 can significantly affect the COMT metabolic pathway of L-dopa. Copyright © 2009 John Wiley & Sons, Ltd. (Source: Phytotherapy Research)

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  Addex ADX48621 Positive Primate Parkinson's Data

Addex Pharmaceuticals (SWISS: ADXN), the allosteric modulation company, announced that in a non-human primate model of Parkinson's disease (PD) levodopa induced dyskinesia (LID), ADX48621 statistically and significantly inhibited LID. More specifically, the compound inhibited dose dependently both chorea and dystonia, the two major components of LID, without affecting the beneficial effects of levodopa. There is currently no approved treatment available for PD-LID. (Source: Parkinson's Disease News From Medical News Today)

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  Addex ADX48621 Positive Primate Parkinson's Data

Addex Pharmaceuticals (SWISS: ADXN), the allosteric modulation company, announced that in a non-human primate model of Parkinson's disease (PD) levodopa induced dyskinesia (LID), ADX48621 statistically and significantly inhibited LID. (Source: Health News from Medical News Today)

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  Addex ADX48621 Positive Primate Parkinson's Data

Addex Pharmaceuticals (SWISS: ADXN), the allosteric modulation company, announced that in a non-human primate model of Parkinson's disease (PD) levodopa induced dyskinesia (LID), ADX48621 statistically and significantly inhibited LID... (Source: Parkinson's Disease News From Medical News Today)

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  Importance of membrane-bound catechol-O-methyltransferase in L-DOPA metabolism: a pharmacokinetic study in two types of Comt gene modified mice

Conclusions and implications: In S-COMT-deficient mice, MB-COMT in the liver and the duodenum is able to O-methylate about one-half of exogenous L-DOPA. Sexual dimorphism and activity of the two COMT isoforms seems to be tissue specific and more prominent in peripheral tissues than in the brain. (Source: British Journal of Pharmacology)

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  Homocysteine-lowering therapy or antioxidant therapy for bone loss in Parkinson's disease

We investigated whether homocysteine (Hcy)- lowering therapy or an antioxidant prevented bone loss in Parkinson's disease (PD) patients taking levodopa. Forty-two PD patients with low bone mineral density (BMD) taking levodopa were randomly assigned to Hcy-lowering therapy (5 mg folate and 1500 [mu]g vitamin B12 daily), [alpha]-lipoic acid ([alpha]-LA) therapy (1200 mg daily), or control groups. Primary outcomes were BMD changes from baseline to 12 months. Secondary outcomes were changes in Hcy level, and C-telopeptide (CTX) levels at 12 months. Forty-one patients completed the study. Hcy-lowering therapy resulted in significantly greater BMD changes at the lumbar spine (4.4%), total femur (2.8%), and femur shaft (2.8%) than control (P = 0.005-0.023). BMD changes in the [alpha]-LA therapy ...

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  The effect of l-Dopa administration on pursuit ocular movements in suspected Parkinson’s disease

The objective of this study is to evaluate pursuit ocular movements (POM) by using a vision-based non-intrusive eye tracker, in patients with suspected Parkinson’s disease (PD), before and after l-Dopa administration. We studied ten patients with suspected diagnosis of idiopathic PD. We compared POM values to those of a group of normal controls (NC), and evaluated them before and after l-Dopa administration. Unified Parkinson’s Disease Rating Scale (UPDRS) motor subscores improved significantly (p = 0.001). At baseline, values of POM were lower in suspected PD patients than in NC (p = 0.01). One hour after l-Dopa administration, POM values correlated with UPDRS motor subscore (p = 0.01). We used a recent method, a new vision-based non-intrusive eye track...

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  The FRAGAMP study: environmental and genetic factors in Parkinson’s disease, methods and clinical features

Abstract  The Fattori di Rischio Ambientali e Genetici Associati alla Malattia di Parkinson (FRAGAMP) study is a multicenter case–control study carried out to evaluate the possible role of environmental and genetic factors in Parkinson’s disease (PD). Cases and controls were enrolled from five Movement Disorder centers in Central-Southern Italy. PD was diagnosed according to Gelb’s criteria while the control groups consisted of the spouses of the enrolled patients or of healthy controls matched by age and area of residence. Cases and controls underwent a standardised questionnaire and a blood sample was taken for molecular analyses. At the end of the study 585 cases and 481 control subjects (287 spouse-controls and 194 generic-controls) were enrolled. Patients had a H...

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  Transient gender-related effects in Parkinson’s disease patients with subthalamic stimulation

Abstract  Little is known about the gender-related long-term efficacy and safety after subthalamic nucleus deep brain stimulation (STN DBS) implant for Parkinson’s disease (PD), although some differences could be expected as recently stated in a short-term report. We assessed the possible gender-related differences in clinical outcome and disease progression along a 5-year period after STN DBS for PD. A prospective cohort of PD patients who underwent STN DBS and reached the 5-year follow-up (FU) was considered. Clinical outcome, disease progression and side effects were assessed at baseline and 1, 3, and 5 years after surgery. Eleven men and nine women were included in the study. At baseline, no inter-gender difference of age at implant, disease duration and severity...

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  Safety and tolerability of putaminal AADC gene therapy for Parkinson disease

Conclusion: This study provides class IV evidence that bilateral intrastriatal infusion of adeno-associated viral type 2 vector containing the human AADC gene improves mean scores on the Unified Parkinson’s Disease Rating Scale by approximately 30% in the on and off states, but the surgical procedure may be associated with an increased risk of intracranial hemorrhage and self-limited headache. (Source: Neurology)

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  Subthalamic Nucleus Deep Brain Stimulation Improves Saccades in Parkinson's Disease

Conclusions. These results demonstrate that STN DBS has differential effects on the parameters of visually guided and internally generated saccades. These effects may be mediated by the influence of STN DBS on cortical ocular motor areas, the basal ganglia, ocular motor loop, or downstream structures such as the brainstem saccade generating circuits. (Source: Neuromodulation)

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  The dopaminergic neurons of the A11 system in RLS autopsy brains appear normal

This study found no significant difference between RLS or control cases on any measure used: TH (+) cell volume, fractional GFAP staining, or general histological examination. Nor was there histological indication of any significant inflammation or concurrent ongoing pathology in these RLS cases. The findings do not support the concept of dramatic cell loss or of a neurodegenerative process in the A11 hypothalamic region of patients with RLS. However, that does not exclude the possibility that the A11 system is involved in RLS symptoms. Changes at the cellular level in dopaminergic metabolism or at the distal synapse with changes in receptors or transporters were not evaluated in this study. (Source: Sleep Medicine)

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  CARBIDOPA AND LEVODOPAtablet [Mylan Pharmaceuticals Inc.]

Updated Date: Nov 12, 2009 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST))

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  HIV-associated parkinsonism with levodopa-induced dyskinesia and response to highly-active antiretroviral therapy

No abstract. (Source: Movement Disorders)

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  Comparing bromocriptine effects with levodopa effects on bladder function in Parkinson's disease

To evaluate the effects of bromocriptine on bladder function in Parkinson's disease (PD) patients and compare these effects with those of (L-dopa). We recruited 8 patients with PD. Urodynamic study (UDS) was performed before and 1 hour after administering 100 mg L-dopa/decarboxylase inhibitor (DCI) and 2.5 hours after administering 7.5 mg bromocriptine. After the bromocriptine administration, urinary urgency aggravated. UDS revealed a decreased bladder volume at which detrusor overactivity (DO) was initiated, a decreased bladder volume at first sensation of bladder filling (FSV) (P < 0.05), an increased maximum Watts Factor value (WFmax) (detrusor contractility), a decreased Abrams-Griffiths (AG) number (urethral obstruction), and a decreased postvoid residual (PVR) (P < 0.01). Similarly, ...

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  Levodopa response in early Parkinson's disease

To further characterize the short-term levodopa response in early PD, we performed a retrospective analysis of the ELLDOPA study which randomized 361 early PD subjects to placebo, levodopa 150, 300, or 600 mg/day. We evaluated change in UPDRS motor scores (UPDRSm) from baseline to weeks 9 and 24, and identified changes in UPDRSm that best discriminated treatment with levodopa from placebo. Linear regressions were used to determine associations between baseline characteristics and changes in UPDRSm. Mean percent improvement in UPDRSm in levodopa-treated subjects was greater than that for placebo-treated subjects (27.4% vs. 5.8% at 9 weeks, P < 0.001 and 26.2% vs. 4.0% at 24 weeks, P < 0.001). UPDRSm change at 9 weeks ranged from -92.9% (improvement) to 85.7% (worsening) for levodopa and -86...

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  [Review] Chronic dopaminergic stimulation in Parkinson's disease: from dyskinesias to impulse control disorders

Dopamine is an essential neurotransmitter for many brain functions, and its dysfunction has been implicated in both neurological and psychiatric disorders. Parkinson's disease is an archetypal disorder of dopamine dysfunction characterised by motor, cognitive, behavioural, and autonomic symptoms. While effective for motor symptoms, dopamine replacement therapy is associated not only with motor side-effects, such as levodopa-induced dyskinesia, but also behavioural side-effects such as impulse control disorders (eg, pathological gambling and shopping, binge eating, and hypersexuality), punding (ie, abnormal repetitive non-goal oriented behaviours), and compulsive medication use. We review clinical features, overlapping molecular mechanisms, and a specific cognitive mechanism of habit learni...

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  Effect of subthalamic deep brain stimulation on postural abnormality in Parkinson disease.

Conclusions Postural abnormality in patients with PD could be ameliorated by STN DBS, and therefore surgery should be considered before irreversible spinal deformity develops. PMID: 19895200 [PubMed - as supplied by publisher] (Source: Journal of Neurosurgery)

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  Periodic leg movements and REM sleep without atonia in Parkinson's disease with camptocormia

Camptocormia (a flexion of the trunk that only appears when standing or walking) affects a minority of patients with Parkinson's disease (PD). As it responds poorly to levodopa and is associated with reduced midbrain and pons volume, it may result from non-dopaminergic, brainstem lesions. As several sleep abnormalities in PD also result from non-dopaminergic brainstem lesions, we monitored sleep in 24 non-demented PD patients with (n = 12) and without (n = 12) camptocormia and in 12 controls. Nearly half (42%) patients with camptocormia had abnormal periodic leg movement indices (>15/h), versus 17% patients without camptocormia and 8% of controls (p = 0.02). In addition, the percentage of enhanced muscle activity during REM sleep (measured on the chin and on the limb muscles) tended to be ...

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  Longitudinal study of the levodopa motor response in Parkinson's disease: Relationship between cognitive decline and motor function

In this prospective study of 34 patients with Parkinson's disease (PD), measurements of the short duration levodopa motor response have been performed every 3 years in defined off states. The mean time from initiation of levodopa treatment was 14.8 years, and 17 patients survived to the latest assessment stage. Off phase motor function worsened at a yearly rate of 2.2% of the maximum disability score. The magnitude of the levodopa response is well preserved as the disease progresses, and patients who developed motor fluctuations maintained better on phase motor function than nonfluctuators (P = 0.01). Ten patients, of whom 5 survive, developed dementia. There was no difference in pretreatment disability or initial levodopa response between demented and nondemented subjects. However, dement...

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  CARBIDOPA AND LEVODOPAtablet [Goldline Laboratories, Inc.]

Updated Date: Nov 2, 2009 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST))

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  Review paper Optimisation of treatment of Parkinson’s disease with levodopa

This article presents the major strategies for individualisation and optimisation of levodopa therapy. The relationship between pharmacokinetic and pharmacodynamic effects of levodopa is discussed. Pharmacokinetic parameters in different stages of Parkinson’s disease are interpreted. Moreover, the main differences in pharmacokinetics of levodopa formulations and routes of administration are presented. The authors also suggest methods to increase efficacy and safety of levodopa therapy in patients with Parkinson’s disease. (Source: Articles of Polish Journal of Neurology and Neurosurgery - TERMEDIA publishing house)

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  Alleviation of off-period dystonia in Parkinson disease by a microlesion following subthalamic implantation.

Conclusions The author postulated that off-period dystonia alleviation may reflect both a microsubthalamotomy and micropallidotomy effect. They hypothesize, moreover, that the microlesion could play a role in the 6-month postoperative outcome. PMID: 19877801 [PubMed - as supplied by publisher] (Source: Journal of Neurosurgery)

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  [Fifteen years history of Parkinson's disease in Spain (1963-1977). A personal recollection.]

Authors: Gimenez-Roldan S Parkinson's disease (PD) and movement disorders, currently one of the leading subspecialties among Spanish neurologists, raised only modest interest during the seventies. This is well reflected in Revista de Neurologia, the first journal entirely devoted to Neurology in Spain. Along five years (1973-1977) only 3% out of papers published were devoted to this subject. The functions of the basal ganglia were poorly known. PD was regarded as a disorder of muscular tone, rigidity playing a pivotal role to explain most, if not all, parkinsonian signs. 'Arteriosclerotic parkinsonism', whatever the symptoms might be, was applied to any form of parkinsonism occurring after the age of sixty. Such cases were usually treated by general practitioners, while younger patient...

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  Determination of related substances of levodopa including the R-enantiomer by CE

A CE assay for the simultaneous determination of the impurities of levodopa listed in the European Pharmacopoeia including the (R)-enantiomer was developed and validated. The analysis was performed in a fused-silica capillary employing sulfated [beta]-cyclodextrin as chiral selector at an applied voltage of 20 kV and a temperature of 18°C. The optimized background electrolyte consisted of 0.1 M sodium phosphate buffer, pH 2.0, containing 6 mg/mL sulfated [beta]-cyclodextrin. L-phenylalanine was used as the internal standard. The assay was validated in the range of 0.1-1.0% for the impurities at a concentration of levodopa of 2 mg/mL. The effect of different batches of sulfated [beta]-cyclodextrin was investigated using levodopa and L-tyrosine as critical pair. The method was applied to de...

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  Serpentine tongue: A rare manifestation following initiation of levodopa therapy in a patient with Parkinson's disease

We report an interesting observation in a patient with PD who developed abnormal movements involving only the tongue soon after the introduction of levodopa and responded well to substitution of levodopa with dopamine agonist. (Source: Parkinsonism and Related Disorders)

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  A Swedish family with de novo α-synuclein A53T mutation: Evidence for early cortical dysfunction

Abstract: A de novo α-synuclein A53T (p.Ala53 Th; c.209G > A) mutation has been identified in a Swedish family with autosomal dominant Parkinson's disease (PD). Two affected individuals had early-onset (before 31 and 40 years), severe levodopa-responsive PD with prominent dysphasia, dysarthria, and cognitive decline. Longitudinal clinical follow-up, EEG, SPECT and CSF biomarker examinations suggested an underlying encephalopathy with cortical involvement. The mutated allele (c.209A) was present within a haplotype different from that shared among mutation carriers in the Italian (Contursi) and the Greek-American Family H kindreds. One unaffected family member carried the mutation haplotype without the c.209A mutation, strongly suggesting its de novo occurrence within this family. Furthe...

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  SINEMET (Carbidopa And Levodopa) Tablet, Extended Release [Bristol-Myers Squibb Pharma Company]

Updated Date: Oct 22, 2009 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST))

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  Synaptic recruitment of AMPA glutamate receptor subunits in levodopa-induced dyskinesia in the MPTP-lesioned nonhuman primate

No abstract. (Source: Synapse)

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  Mirapexin prolonged release tablets (pramipexole) - New Formulation

Source: Manufacturer notification, eMC (electronic Medicines Compendium) Area: Other Library Updates > SPC Changes New Formulation Mirapexin prolonged-release tablets are a once-a-day oral formulation of pramipexole. Mirapexin is indicated for treatment of the signs and symptoms of idiopathic Parkinson's disease, alone (without levodopa) or in combination with levodopa. (Source: NeLM - SPC Changes)

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  Once daily Mirapexin® (pramipexole prolonged release) for Parkinson's disease launched in the UK

Source: No information given Area: News Boehringer-Ingelheim has launched a prolonged-release (once-daily) formulation of pramipexole (Mirapexin®) for the treatment of the signs and symptoms of idiopathic Parkinson's disease, for use as monotherapy or in combination with levodopa.  According to the press release, 84.5% of patients participating in a recent double-blind trial successfully switched to Mirapexin prolonged release overnight; the majority of these were able to switch at the same daily dose (no specific study details presented).  Please see the attached press release for further information. (Source: NeLM - News)

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  Levodopa/tolcapone: Hypersexuality treated with carbamazepine in an elderly patient: case report

(Source: Reactions)

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  Med Sci Monit 2009; 15(11):BR339-348 "The effect of memantine and levodopa/carbidopa on the responses of phrenic nerve-diaphragm preparations from aged rats"

Conclusions: Memantine inhibits neuromuscular transmission in vitro and with in vivo treatment. LD/CD treatment enhances neuromuscular transmission. Clinical implications need further investigation. (Source: Medical Science Monitor)

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  Novel mutation affecting the pterin-binding site of PTS gene and review of PTS mutations in Thai patients with 6-pyruvoyltetrahydropterin synthase deficiency

In conclusion, severe neurological impairment from BH4 deficiency could be prevented by newborn screening for HPA and proper metabolic management. However, pterin analysis for early diagnosis of BH4 deficiency is still not available in most developing countries. Content Type Journal ArticleCategory CASE REPORTDOI 10.1007/s10545-009-1221-xAuthors N. Vatanavicharn, Faculty of Medicine Siriraj Hospital Division of Medical Genetics, Department of Pediatrics 2 Prannok Road, Bangkoknoi Bangkok Thailand 10700C. Kuptanon, Faculty of Medicine Siriraj Hospital Division of Medical Genetics, Department of Pediatrics 2 Prannok Road, Bangkoknoi Bangkok Thailand 10700S. Liammongkolkul, Faculty of Medicine Siriraj Hospital Division of Medical Genetics, Department of Pediatrics 2 Prannok Road, Bangko...

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  Gout chemical 'may help' Parkinon's

This study involved 800 people participating in the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) randomised controlled trial. This two-year Canadian trial enrolled people with early Parkinson’s disease (without severe symptoms and not currently using medications; average age 62). It aimed to test the theory that long-term treatment with monoamine oxidase type B inhibitor deprenyl (selegiline hydrochloride) and/or the antioxidant alpha-tocopherol would delay the onset of disability. For the purposes of this study, the researchers took a pre-treatment blood sample from 774 of the participants to check urate levels, and a sample of cerebrospinal fluid from 713 participants. The DATATOP researchers used clinical disability requiring levodopa therapy as the primary ...

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  Gout chemical 'may help' Parkinson's

This study involved 800 people participating in the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) randomised controlled trial. This two-year Canadian trial enrolled people with early Parkinson’s disease (without severe symptoms and not currently using medications; average age 62). It aimed to test the theory that long-term treatment with monoamine oxidase type B inhibitor deprenyl (selegiline hydrochloride) and/or the antioxidant alpha-tocopherol would delay the onset of disability. Researchers took a pre-treatment blood sample from 774 of the participants to check urate levels, and a sample of cerebrospinal fluid from 713 participants. The DATATOP researchers used clinical disability requiring levodopa therapy as the primary endpoint of the clinical trial. The ...

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  Boehringer Ingelheim receives approval from the European Commission for Mirapexin®/Sifrol® prolonged-release, once daily tablet for the treatment of Parkinson`s disease

Ingelheim/Germany, 14 October 2009 – Boehringer Ingelheim today announced that the Mirapexin®/Sifrol® (pramipexole) new prolonged-release, once daily tablet has been granted marketing authorisation by the European Commission in all EU/EEA*) countries for the treatment of early and advanced idiopathic Parkinson’s disease (PD). The approval was based on the submission of clinical trial results showing that the new formulation can offer an efficacy and safety profile comparable to the immediate release tablet taken three times daily.1-6 In addition to clinical trial results that confirm the important therapeutic benefits of the new formulation when administered in a convenient once-a-day regimen, a further trial has shown that patients already taking Mirapexin®/Sifrol® immediate re...

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  Boehringer Ingelheim receives approval from the European Commission for Mirapexin®/Sifrol® prolonged-release, once daily tablet for the treatment of Parkinson`s disease

Ingelheim/Germany, 14 October 2009 - Boehringer Ingelheim today announced that the Mirapexin®/Sifrol® (pramipexole) new prolonged-release, once daily tablet has been granted marketing authorisation by the European Commission in all EU/EEA*) countries for the treatment of early and advanced idiopathic Parkinson`s disease (PD). The approval was based on the submission of clinical trial results showing that the new formulation can offer an efficacy and safety profile comparable to the immediate release tablet taken three times daily.1-6 In addition to clinical trial results that confirm the important therapeutic benefits of the new formulation when administered in a convenient once-a-day regimen, a further trial has shown that patients already taking Mirapexin®/Sifrol® imme...

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  ORIGINAL CONTRIBUTION: Urate as a Predictor of the Rate of Clinical Decline in Parkinson Disease

Conclusions  Higher serum and cerebrospinal fluid urate concentrations at baseline were associated with slower rates of clinical decline. The findings strengthen the link between urate concentration and PD and the rationale for considering central nervous system urate concentration elevation as a potential strategy to slow PD progression.Published online October 12, 2009 (doi:10.1001/archneurol.2009.247). (Source: Archives of Neurology)

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  Urate as a Predictor of the Rate of Clinical Decline in Parkinson Disease [Original Contribution]

Conclusions  Higher serum and cerebrospinal fluid urate concentrations at baseline were associated with slower rates of clinical decline. The findings strengthen the link between urate concentration and PD and the rationale for considering central nervous system urate concentration elevation as a potential strategy to slow PD progression.Published online October 12, 2009 (doi:10.1001/archneurol.2009.247). (Source: Archives of Neurology)

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  Dopaminergic Neuromodulation of Semantic Processing: A 4-T fMRI Study with Levodopa

There is emerging evidence that alterations in dopaminergic transmission can influence semantic processing, yet the neural mechanisms involved are unknown. The influence of levodopa (L-DOPA) on semantic priming was investigated in healthy individuals (n = 20) using event-related functional magnetic resonance imaging with a randomized, double-blind crossover design. Critical prime–target pairs consisted of a lexical ambiguity prime and 1) a target related to the dominant meaning of the prime (e.g., bank–money), 2) a target related to the subordinate meaning (e.g., fence–sword), or 3) an unrelated target (e.g., ball–desk). Behavioral data showed that both dominant and subordinate meanings were primed on placebo. In contrast, there was preserved priming of dominant mea...

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  The dopamine D2 receptor partial agonist aplindore improves motor deficits in MPTP-treated common marmosets alone and combined with l-dopa

Abstract  Dopamine replacement therapy in Parkinson’s disease (PD) using l-dopa is invariably associated with a loss of drug efficacy (“wearing off”) and the onset of dyskinesia. The use of dopamine receptor partial agonists might improve therapeutic benefit without increased dyskinesia expression but may antagonise the effects of l-dopa. We now examine the effects of the novel high affinity, dopamine D2 receptor partial agonist, aplindore alone and in combination with l-dopa in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated common marmoset. In non-dyskinetic MPTP treated animals, aplindore (0.05–1.0 mg/kg p.o.) produced a dose-dependent reversal of motor disability and an increase in locomotor activity that was maximal at doses of 0.2 mg/kg...

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  Short-Term Cost and Health Consequences of Duodenal Levodopa Infusion in Advanced Parkinsons Disease in Sweden: An Exploratory Study

(Source: Applied Health Economics and Health Policy)

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  The U937 macrophage cell line expresses enzymatically active l-Dopa decarboxylase

Abstract: In the present study we demonstrate that enzymatically active l-Dopa decarboxylase (DDC) is expressed in U937 cells, an important model of human macrophage function. The mRNA coding for the enzyme was found to be of the neural-type. DDC was detected in both the soluble and membrane fractions. The active molecule is released from the membrane fraction in the absence of detergent. Furthermore, exposure of U937 cells to carbidopa and dopamine considerably affected cell viability. The expression of enzymatically active DDC shows the endogenous production of dopamine in U937 cells and raises new questions about the enzyme's involvement in immune responses. (Source: Journal of Neuroimmunology)

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  Role of an electronic armband in motor function monitoring in patients with Parkinson's disease

Abstract: Objective: Levodopa replacement still is the gold standard for the management of Parkinson's disease (PD). Long-term treatment with levodopa is frequently associated with motor fluctuations. A low-protein (LP) dietary regimen has proved to be effective in reducing this adverse effect, but has been associated with weight loss, probably due to increased energy expenditure. A new wearable device (SenseWear Armband [SWA]) has recently been introduced into clinical practice. It is designed to monitor physical activity continuously and provide estimates of energy consumption. We assessed its role in measuring the effects of dietary regimens on motor function in PD.Methods: Six patients with levodopa-treated PD and motor fluctuations were asked to follow a balanced diet (protein 1g · k...

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  Pharmacokinetic evaluation and modeling of formulated levodopa intranasal delivery systems.

In conclusion, the L-dopa nasal delivery system could be used as a good rescue therapy for PD patients who experience symptom fluctuation with oral L-dopa administration. PMID: 19804823 [PubMed - as supplied by publisher] (Source: European Journal of Pharmaceutical Sciences)

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  Deal watch : Santhera licenses novel dyskinesia therapy to Biovail

Deal watch : Santhera licenses novel dyskinesia therapy to Biovail Nature Reviews Drug Discovery 8, 762 (2009). doi:10.1038/nrd3009 Biovail Laboratories has signed an agreement with Santhera Pharmaceuticals, entitling Biovail to the US and Canadian rights to develop and commercialize fipamezole (also known as JP-1730), for the treatment of levodopa-induced dyskinesia in Parkinson's disease. The agreement involves an upfront payment of US$8 million from (Source: Nature Reviews Drug Discovery)

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  Reduction of the postexcitatory cortical inhibition upon paired-click auditory stimulation in patients with Parkinson’s disease

Abstract: Objectives: The aims of this study were: to investigate the postexcitatory inhibition of cortical evoked potentials on auditory paired-click stimulation in patients with Parkinson’s disease (PD), to analyze the correlation of N1–P2 amplitude ratios (A2/A1) with latency of the P300 auditory event-related potential and to determine the influence of Levodopa intake on postexcitatory inhibition and P300 latency.Methods: The central (Cz) auditory evoked potentials were recorded in 61 patients with PD and 21 age-matched healthy subjects.Results: Postexcitatory inhibition in auditory cortex in PD was significantly reduced for interstimulus intervals 500, 700 and 900ms compared to control group. The degree of this reduction correlated positively with the potential P300 latency and ne...

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  Mylan Receives FDA Approval for Generic Version of Parkinson's Treatment Sinemet(R)

PITTSBURGH, Sept. 30 (HSMN NewsFeed) -- Mylan Inc. (Nasdaq: MYL ) today announced that its subsidiary Mylan Pharmaceuticals Inc. has received approval from the U.S. Food and Drug Administration (FDA) for its Abbreviated New Drug Application (ANDA) for Ca... Biopharmaceuticals, Generics, Neurology, FDAMylan, Mylan Pharmaceuticals, Carbidopa, Levodopa, Sinemet (Source: HSMN NewsFeed)

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  Methylenetetrahydrofolate reductase polymorphisms and plasma homocysteine in levodopa-treated and non-treated Parkinson's disease patients

We examined whether connecting both polymorphisms influences the effect of levodopa on Hcy. MTHFR genotypes and Hcy, vitamin B12, and folate levels were determined in 48 levodopa-treated PD patients (PD-L), 28 non-treated PD patients (PD-N) and 110 controls. Hcy was remarkably higher in PD-L than in PD-N and controls (p (Source: Journal of the Neurological Sciences)

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  Impax Pharmaceuticals Reports Positive Results Of Phase II Trial Of IPX066, A Novel Formulation Of Carbidopa-Levodopa For Parkinson's Disease

Impax Pharmaceuticals, the brand products division of Impax Laboratories, Inc. (NASDAQ: IPXL) reported the positive results from a recently completed Phase II trial of its late-stage Parkinson's Disease drug candidate IPX066 In this cross-over trial, IPX066 reduced subjects' "off" time during waking hours by 2 hours compared to Sinemet (3.8 hours of "off" time for IPX066 vs. 5. (Source: Health News from Medical News Today)

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  Successful perioperative management of patients with Parkinson’s disease following gastrointestinal surgery: Report of three cases

This report presents the cases of three patients with Parkinson’s disease who underwent gastrointestinal surgery and had no serious postoperative complications. Antiparkinsonian medications were reduced before surgery and replaced by an intravenous infusion of levodopa until the patients could take oral antiparkinson drugs after surgery to prevent malignant syndrome or exacerbate parkinsonism. Prokinetics were also used for the prevention of paralytic ileus. These cases demonstrate an effective method to administer antiparkinson drugs during perioperative management of patients with Parkinson’s disease and also indicate that sufficient doses of antiparkinson drugs can control the symptoms of parkinsonism and prevent complications in cases of surgery with parkinsonism. Content ...

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  CARBIDOPA AND LEVODOPA Tablet CARBIDOPA AND LEVODOPA (Carbidopa And Levodopa) Tablet [Apotex Corp.]

Updated Date: Sep 23, 2009 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST))

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  Independent validation of the scales for outcomes in Parkinson's disease-autonomic (SCOPA-AUT)

Conclusions: Despite its heterogeneous content, which determines some weaknesses in the psychometric attributes of its subscales, SCOPA-AUT is an acceptable, consistent, valid and precise scale. (Source: European Journal of Neurology)

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  Impax Pharmaceuticals Reports Positive Results of Phase II Trial of IPX066, a Novel Formulation of Carbidopa-Levodopa for Parkinson's Disease

HAYWARD, Calif.--(BUSINESS WIRE)--Sep 21, 2009 - Impax Pharmaceuticals, the brand products division of Impax Laboratories, Inc. (NASDAQ: IPXL) today reported the positive results from a recently completed Phase II trial of its late-stage... (Source: Drugs.com - Clinical Trials)

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  Apomorphine/levodopa: Psychiatric disorders: case report

(Source: Reactions)

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  Levodopa abuse, overdose: Dopamine dysregulation syndrome in an elderly patient: case report

(Source: Reactions)

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  Expression of catechol-O-methyltransferase in the brain and periphery of normal and MPTP-treated common marmosets

Abstract  Catechol-O-methyltransferase (COMT) inhibition is widely used to potentiate the effects of levodopa in Parkinson’s disease but the effects of nigral dopaminergic cell loss and levodopa treatment on COMT activity are not known. The present study investigated the expression of COMT in the brain and liver of normal common marmosets, and animals treated with MPTP and those treated with levodopa to induce dyskinesia. Reverse transcript PCR demonstrated the expression of COMT mRNA in the liver, cortex and striatum of normal marmosets. Using Western blotting, the presence of two subunits of COMT protein, membrane bound COMT (MB-COMT) and soluble COMT (S-COMT), was shown in the liver, cortex and striatum of normal marmosets. Quantitative analysis of the MB-COMT and S-CO...

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