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Electroencephalography and Clinical... Mar 1987Bereitschaftspotentials (BPs) prior to extension movements of the index finger were studied in normal subjects and in patients with Parkinson's disease. In both, BPs...
Bereitschaftspotentials (BPs) prior to extension movements of the index finger were studied in normal subjects and in patients with Parkinson's disease. In both, BPs were studied before and after L-DOPA therapy; in addition, the normal subjects were studied after dopamine antagonists. In both patients and normal subjects, L-DOPA caused an increase in the amplitude of the early part of the BP and of the point of peak negativity, just prior to EMG onset (N1) but it did not cause an increase of the late lateralized part of the BP (NS' of Shibasaki); in normal subjects dopaminergic antagonists caused a decrease in the amplitude of the N1. Control experiments suggested that the change caused by L-DOPA was not the result of slower movement or poorer triggering when OFF drugs. For patients with Parkinson's disease there was no correlation between the change in their peak BP negativity (N1) after L-DOPA and their change in clinical mobility; in addition, there was no difference in the peak BP negativity of patients OFF therapy and that of age-matched normals, though there was a slight decrease in the amplitude of the early part of the BP for the patients with Parkinson's disease; this was the same part that had been enlarged by L-DOPA therapy. These findings suggest that the N1 is not affected by Parkinson's disease and that the effect of dopaminergic drugs on the N1 is mediated by actions on dopaminergic mechanisms elsewhere than in the striatum, perhaps in the cerebral cortex itself. The effect of L-DOPA will need to be taken into account in subsequent studies of the BP in Parkinson's disease.
Topics: Adult; Electroencephalography; Evoked Potentials; Fingers; Humans; Levodopa; Middle Aged; Movement; Parkinson Disease
PubMed: 2434310
DOI: 10.1016/0013-4694(87)90075-7 -
EMBO Molecular Medicine Mar 2023Tyrosine hydroxylase deficiency (THD) is a rare genetic disorder leading to dopaminergic depletion and early-onset Parkinsonism. Affected children present with either a...
Tyrosine hydroxylase deficiency (THD) is a rare genetic disorder leading to dopaminergic depletion and early-onset Parkinsonism. Affected children present with either a severe form that does not respond to L-Dopa treatment (THD-B) or a milder L-Dopa responsive form (THD-A). We generated induced pluripotent stem cells (iPSCs) from THD patients that were differentiated into dopaminergic neurons (DAn) and compared with control-DAn from healthy individuals and gene-corrected isogenic controls. Consistent with patients, THD iPSC-DAn displayed lower levels of DA metabolites and reduced TH expression, when compared to controls. Moreover, THD iPSC-DAn showed abnormal morphology, including reduced total neurite length and neurite arborization defects, which were not evident in DAn differentiated from control-iPSC. Treatment of THD-iPSC-DAn with L-Dopa rescued the neuronal defects and disease phenotype only in THDA-DAn. Interestingly, L-Dopa treatment at the stage of neuronal precursors could prevent the alterations in THDB-iPSC-DAn, thus suggesting the existence of a critical developmental window in THD. Our iPSC-based model recapitulates THD disease phenotypes and response to treatment, representing a promising tool for investigating pathogenic mechanisms, drug screening, and personalized management.
Topics: Dopaminergic Neurons; Induced Pluripotent Stem Cells; Levodopa; Phenotype; Humans
PubMed: 36740977
DOI: 10.15252/emmm.202215847 -
European Neurology 1980Sebum secretion was studied in 14 parkinsonian patients before and after 3 months of treatment with L-dopa. An abnormality of sebum secretion was shown to exist in...
Sebum secretion was studied in 14 parkinsonian patients before and after 3 months of treatment with L-dopa. An abnormality of sebum secretion was shown to exist in parkinsonism. In 7 patients, successfully treated with L-dopa, sebum secretion diminished and its pattern improved. In all patients, in whom L-dopa treatment did not result in noticeable clinical changes, there was no significant modification in sebum secretion. No change was observed in the secretion of sebum of 5 normal control subjects, who were given L-dopa for 1 week.
Topics: Adult; Aged; Female; Humans; Levodopa; Male; Middle Aged; Parkinson Disease; Sebum
PubMed: 7371653
DOI: 10.1159/000115127 -
Neuroscience Research Mar 2003Brain ischemic insult causes glutamate release and resultant neuronal cell death. We here show that L-3,4-dihydroxyphenylalanine (DOPA) is a positive regulatory factor...
Brain ischemic insult causes glutamate release and resultant neuronal cell death. We here show that L-3,4-dihydroxyphenylalanine (DOPA) is a positive regulatory factor for glutamate release elicited by a mild brain insult using in vitro superfused rat striatal slices as a model system. Glucose deprivation for 18 min elicited release of glutamate, DOPA and dopamine (DA). Either tetrodotoxin (TTX) (1 microM) or alpha-methyl-p-tyrosine (alpha-MPT) (1 mM), a tyrosine hydroxylase inhibitor reduced markedly each of these releases. NSD-1015 (20 microM), an aromatic L-amino acid decarboxylase inhibitor restored the inhibition by alpha-MPT of glutamate and DOPA but not DA release. DOPA cyclohexyl ester (DOPA CHE) (0.3-1 microM), a competitive DOPA antagonist, concentration-dependently suppressed aglycemia-induced glutamate release, the effect which was mimicked neither by S-sulpiride nor SCH23390, a DA D(1) or D(2) receptor antagonist, respectively. Zonisamide (1-1000 microM), an anticonvulsant or YM872 (1 microM), an alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) a receptor antagonist produced no effect on aglycemia-induced glutamate release. DOPA CHE thus showed a relatively potent inhibitory action on aglycemia-induced glutamate release among several neuroprotective agents tested.
Topics: Animals; Corpus Striatum; Dihydroxyphenylalanine; Glucose; Glutamic Acid; In Vitro Techniques; Levodopa; Male; Neuroprotective Agents; Rats; Rats, Wistar
PubMed: 12631469
DOI: 10.1016/s0168-0102(02)00237-7 -
Science (New York, N.Y.) Jul 1977In a study of the effect of L-dopa, an intermediate in the biosynthesis of the pigment melanin, on the growth of human and murine melanoma cells a highly selective...
In a study of the effect of L-dopa, an intermediate in the biosynthesis of the pigment melanin, on the growth of human and murine melanoma cells a highly selective inhibition of growth was observed for pigmented cell lines (S91A and human melanoma) as compared to the nonpigmented control cells (amelanotic melanoma S91B, mouse fibroblast L929, and Chinese hamster ovary). There was a correlation between toxicity and the extent of incorporation of radioactively labeled L-dopa by each line.
Topics: Cell Division; Cell Line; Levodopa; Melanoma; Pigmentation
PubMed: 877570
DOI: 10.1126/science.877570 -
Proceedings of the Australian... 1975The results of a clinical trial of enteric coated Levo-dopa are described for nineteen patients with Parkinsonism. Twelve cases comprise the nuclear group and all were... (Comparative Study)
Comparative Study
The results of a clinical trial of enteric coated Levo-dopa are described for nineteen patients with Parkinsonism. Twelve cases comprise the nuclear group and all were intolerant to therapeutic doses of standard Levo-dopa. Seven cases were receiving Levo-dopa for the first time. Treatment periods ranged from three to twelve months. Of the whole group, 84% have improved. Of the poor responders to standard Levo-dopa 58% have improved markedly and the remaining 42% have improved to a moderate degree using clinical criteria. The mean stabilization dose was 1.5 grams daily and using the Mann-Whitney U test the difference is highly significant when comparison is made with the stabilization dose of 3.0 grams for standard Levo-dopa (P less than .001). The method of stabilization is described; the commonest initial stabilization period is three weeks. Side-effects are dose-related. No side-effects have appeared in 60% of the patients and only mild or transient side-effects have appeared in 20%. A characteristic toxic reaction is described. This enteric-coated preparation of the drug appears to control the "on-off" phenomenon in at least 50% of cases with this problem. The preparation is suitable for routine use in outpatients but added care is required to ensure that vitamin tonics are rigorously avoided. Two deaths are recorded during the trial, but analysis shows them to be unrelated causally to the therapy. Enteric coated Levo-dopa is recommended as the primary treatment in all new cases where Levo-dopa therapy is indicated. No adverse interactions have occurred with other commonly used anti-Parkinsonian drugs.
Topics: Adult; Aged; Female; Humans; Levodopa; Male; Middle Aged; Parkinson Disease; Recurrence; Syndrome; Tablets, Enteric-Coated
PubMed: 1215401
DOI: No ID Found -
Journal of Materials Chemistry. B Dec 2023L-3,4-Dihydroxyphenylalanine (L-DOPA) is widely used in Parkinson's disease treatment and is therefore in high demand. Development of an efficient method for the...
L-3,4-Dihydroxyphenylalanine (L-DOPA) is widely used in Parkinson's disease treatment and is therefore in high demand. Development of an efficient method for the production of L-DOPA is urgently required. Nanozymes emulating tyrosine hydroxylase have attracted enormous attention for biomimetic synthesis of L-DOPA, but suffered from heterogeneity. Herein, a spherical porous iron-nitrogen-carbon nanozyme was developed for production of L-DOPA. Tannic acid chelated with ferrous ions to form a tannin-iron coordination framework as a carbon precursor. Iron and nitrogen co-doped carbon nanospheres were assembled an evaporation-induced self-assembly process using urea as a nitrogen source, F127 as a soft template, and formaldehyde as a crosslinker. The nanozyme was obtained after carbonization and acid etching. The nanozyme possessed a dispersive iron atom anchored in the Fe-N coordination structure as an active site to mimic the active center of tyrosine hydroxylase. The material showed spherical morphology, uniform size, high specific surface area, a mesoporous structure and easy magnetic separation. The structural properties could promote the density and accessibility of active sites and facilitate mass transport and electron transfer. The nanozyme exhibited high activity to catalyze the hydroxylation of tyrosine to L-DOPA as tyrosine hydroxylase in the presence of ascorbic acid and hydrogen peroxide. The titer of DOPA reached 1.2 mM. The nanozyme showed good reusability and comparable enzyme kinetics to tyrosine hydroxylase with a Michaelis-Menten constant of 2.3 mM. The major active species was the hydroxyl radical. Biomimetic simulation of tyrosine hydroxylase using a nanozyme with a fine structure provided a new route for the efficient production of L-DOPA.
Topics: Tyrosine 3-Monooxygenase; Levodopa; Carbon; Iron; Porosity; Tannins
PubMed: 37953738
DOI: 10.1039/d3tb01082a -
Bulletin de L'Academie Nationale de... 2015Involuntary movements, or dyskinesia, represent a debilitating complication of levodopa (L-dopa) therapy for Parkinson's disease (PD). L-dopa-induced dyskinesia (LID) is...
Involuntary movements, or dyskinesia, represent a debilitating complication of levodopa (L-dopa) therapy for Parkinson's disease (PD). L-dopa-induced dyskinesia (LID) is ultimately experienced by the vast majority of parkinsonian patients. Loss of dopamine in PD induces complex modifications in cellular signaling with numerous pathways showing altered responses to dopaminergic stimulation. Chronic L-dopa treatment further enhances the signaling alterations. The dopamine D1 receptor (D1R) signaling pathway has consistently been shown to be critically involved in LID genesis and manifestation in the striatum, the basal ganglia input structure. Interestingly, recent studies suggest an impact of structures outside of the basal ganglia in LID expression. The present attempts to provide an overview of our current understanding of LID pathophysiology.
Topics: Dyskinesia, Drug-Induced; Humans; Levodopa; Parkinson Disease
PubMed: 27476302
DOI: No ID Found -
Angewandte Chemie (International Ed. in... Jan 2022Understanding the regulatory mechanisms of exocytosis is essential for uncovering the pathologies of neuronal disorders and developing related pharmaceuticals. In this...
Understanding the regulatory mechanisms of exocytosis is essential for uncovering the pathologies of neuronal disorders and developing related pharmaceuticals. In this work intracellular vesicle impact electrochemical cytometry (IVIEC) measurements with different-sized (50-500 nm radius) open carbon nanopipettes (CNPs) were performed to quantify the vesicular content and release kinetics of specific vesicle populations grouped by orifice sizes. Intracellular vesicles with radius below 100 nm were captured and narrowed between 50 and 100 nm. On the basis of this, single vesicular catecholamine concentrations in the intracellular environment were quantified as 0.23-1.1 M. Our results with L-3,4-dihydroxyphenylalanine (L-DOPA)-exposure indicate that L-DOPA regulates exocytosis by increasing the dense core size and vesicular content while catecholamine concentrations did not show obvious alterations. These were all achieved simultaneously and relatively noninvasively with open CNPs.
Topics: Carbon; Catecholamines; Levodopa; Nanoparticles
PubMed: 34734466
DOI: 10.1002/anie.202113406 -
Brain Research Dec 1991Two separate experiments were conducted to assess the behavioral and biochemical effects of chronic L-dihydroxyphenylalanine (L-DOPA) treatment in rats with unilateral...
Two separate experiments were conducted to assess the behavioral and biochemical effects of chronic L-dihydroxyphenylalanine (L-DOPA) treatment in rats with unilateral 6-hydroxydopamine (6-OHDA) lesions. In this animal model, contralateral rotation provides the behavioral indicator response for L-DOPA activation of the dopamine denervated striatum. Following 30 daily L-DOPA treatments, a subthreshold dose (10 mg/kg) for rotation became suprathreshold and the contralateral rotation induced by a suprathreshold dose (20 mg/kg) became exaggerated. This motoric sensitization to L-DOPA was not reversed by a three-day period of L-DOPA withdrawal. In contrast with the emergence of behavioral sensitization to L-DOPA, biochemical measurements showed that the increase of dopamine metabolite concentrations (DOPAC and HVA) induced by acute L-DOPA treatment became attenuated with chronic treatment. This finding suggests that chronic L-DOPA treatment produces a partial tolerance in the conversion of L-DOPA to extracellular dopamine. The emergence of L-DOPA sensitization-over-stimulation effects was hypothesized to reflect the combined effects of dopamine receptor priming and Pavlovian drug conditioning and to contribute to the emergence of dyskinetic effects of L-DOPA therapy. The partial tolerance observed for dopamine metabolites was hypothesized to represent a decreased conversion of L-DOPA to dopamine which with long-term treatment could progress to an eventual wearing-off effect of L-DOPA therapy.
Topics: 3,4-Dihydroxyphenylacetic Acid; Animals; Apomorphine; Carbidopa; Corpus Striatum; Denervation; Drug Tolerance; Functional Laterality; Homovanillic Acid; Levodopa; Male; Motor Activity; Oxidopamine; Rats; Rats, Inbred Strains; Substance Withdrawal Syndrome
PubMed: 1814568
DOI: 10.1016/0006-8993(91)91399-l