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Spectrochimica Acta. Part A, Molecular... Oct 2023L-DOPA, or l-3,4-dihydroxyphenylalanine is an aromatic amino acid, which plays a significant role in human metabolism as a precursor of important neurotransmitters. We...
L-DOPA, or l-3,4-dihydroxyphenylalanine is an aromatic amino acid, which plays a significant role in human metabolism as a precursor of important neurotransmitters. We develop a fast and simple colorimetric method for the detection of L-DOPA in biological fluids. The method is based on the reduction of silver ions with L-DOPA and the subsequent formation of L-DOPA stabilized silver nanoparticles (Ag NPs). In this novel approach, L-DOPA works as both reducing and stabilizing agent, which provides selectivity and simplifies the procedure. HR-TEM images show very narrow Ag NPs distribution with an average size of 24 nm. Such sensor design is suggested for the first time. We also calculate vertical ionization potential, vertical electron affinity, and Gibbs free energy change of different ionic forms of L-DOPA and amino acids at the M06-2X/def2-TZVP level for the gas phase in comparison with that of silver. A model of silver ions reduction by aromatic amino acids is proposed: the ionic forms with charge -1 are suggested to reduce silver ions. High selectivity against aromatic amino acids, dopamine and serotonin is achieved by tuning pH and involving two L-DOPA forms with charged both hydroxyphenolate and carboxylate groups in the stabilization of uniform-sized Ag NPs. The method is applicable for the determination of L-DOPA in human serum with the 50 nM limit of detection and the linear range up to 5 μM. Ag NPs formation and coloring the solution proceeds in a few minutes. The suggested colorimetric method has potential application in clinical trials.
Topics: Humans; Levodopa; Metal Nanoparticles; Silver; Colorimetry
PubMed: 37182251
DOI: 10.1016/j.saa.2023.122810 -
Movement Disorders : Official Journal... Jan 2015Levodopa (L-dopa) has been at the forefront of antiparkinsonian therapy for a half century. Recent advances in functional brain imaging have contributed substantially to... (Review)
Review
Levodopa (L-dopa) has been at the forefront of antiparkinsonian therapy for a half century. Recent advances in functional brain imaging have contributed substantially to the understanding of the effects of L-dopa and other dopaminergic treatment on the activity of abnormal motor and cognitive brain circuits in Parkinson's disease patients. Progress has also been made in understanding the functional pathology of dyskinesias, a common side effect of l-dopa treatment, at both regional and network levels. Here, we review these studies, focusing mainly on the new mechanistic insights provided by metabolic brain imaging and network analysis.
Topics: Animals; Antiparkinson Agents; Cerebral Cortex; Cognition Disorders; Humans; Levodopa; Neuroimaging; Parkinson Disease; Regional Blood Flow
PubMed: 25296957
DOI: 10.1002/mds.26041 -
BMC Medicine Oct 2022Parkinson's disease (PD) is the second most common neurodegenerative disease in middle-aged and elderly populations, whereas there is no cure for PD so far. Novel animal...
BACKGROUND
Parkinson's disease (PD) is the second most common neurodegenerative disease in middle-aged and elderly populations, whereas there is no cure for PD so far. Novel animal models and medications await development to elucidate the aetiology of PD and attenuate the symptoms, respectively.
METHODS
A neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), was used in the current study to establish a PD pathologic model in silkworms. The time required to complete specific behaviours was recorded. Dopamine content was detected by ultra-performance liquid chromatography (UPLC). The activity of insect tyrosine hydroxylase (TH) was determined using a double-antibody sandwich method. Oxidative stress was assessed by changes in antioxidant enzyme activity and the content of oxidative products.
RESULTS
MPTP-treated silkworms were characterized by impaired motor ability, reduced dopamine content, and elevated oxidative stress level. The expression of TH, a dopamine biosynthetic enzyme within dopaminergic neurons in the brain, was significantly reduced, indicating that dopaminergic neurons were damaged. Moreover, MPTP-induced motility impairment and reduced dopamine level in the silkworm PD model could be rescued after feeding a combination of levodopa (L-dopa [LD]) and carbidopa (CD). MPTP-induced oxidative damage was also alleviated, in ways consistent with other PD animal models. Interestingly, administration of Lycium barbarum polysaccharide (LBP) improved the motor ability, dopamine level, and TH activity, and the oxidative damage was concomitantly reduced in the silkworm PD model.
CONCLUSIONS
This study provides a promising animal model for elucidating the pathogenesis of PD, as well as a relevant preliminary drug screening (e.g., LBP) and evaluation.
Topics: Animals; Mice; 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Antioxidants; Disease Models, Animal; Dopamine; Levodopa; Mice, Inbred C57BL; Tyrosine 3-Monooxygenase; Parkinson Disease, Secondary; Drugs, Chinese Herbal
PubMed: 36303171
DOI: 10.1186/s12916-022-02621-9 -
Expert Opinion on Drug Delivery 2023Parkinson's disease (PD) is the second most common neurodegenerative disease and is growing in prevalence and disability. The standard treatment for PD is oral levo-dopa... (Review)
Review
INTRODUCTION
Parkinson's disease (PD) is the second most common neurodegenerative disease and is growing in prevalence and disability. The standard treatment for PD is oral levo-dopa (LD) with carbidopa (CD). As PD progresses, despite higher doses of LD/CD, plasma levels of LD fluctuate, and may be associated with motor fluctuations and dyskinesia.
AREAS COVERED
The development of two new subcutaneous preparations of LD/CD (ND0612 and ABBV-951) for the treatment of motor fluctuations in PD is described in detail. Both reduce motor fluctuations and dyskinesia with minor infusion site adverse events. A third subcutaneous preparation, DIZ102, is in early-stage development.
EXPERT OPINION
The premise for using continuous release LD in advanced PD is that steady state levels of LD will prevent motor fluctuations/dyskinesia, but this is not the whole story, and will limit the benefits of subcutaneous continuous release LD. With its present pump system ND0612 cannot be used as monotherapy, whereas ABBV-951 can be. Having to combine with oral LD/CD will complicate the use of ND0612. Both ND0612 and ABBV-951 only cause modest reductions in OFF time. It is not clear whether these subcutaneous preparations will have more benefits than the intestinal gel, which also reduces OFF time and dyskinesia.
Topics: Humans; Carbidopa; Levodopa; Parkinson Disease; Neurodegenerative Diseases; Drug Combinations; Dyskinesias; Antiparkinson Agents
PubMed: 37634938
DOI: 10.1080/17425247.2023.2253146 -
European Journal of Pharmacology Mar 2015Parkinson׳s disease (PD) is chronic progressive neurodegenerative disorder characterized by profound loss of dopaminergic neurons in the nigrostriatal pathway. It is... (Review)
Review
Parkinson׳s disease (PD) is chronic progressive neurodegenerative disorder characterized by profound loss of dopaminergic neurons in the nigrostriatal pathway. It is recognized by the cardinal clinical features of bradykinesia, rigidity, tremor and postural instability. Current therapeutic options are primarily dopamine replacement strategies that only provide symptomatic improvement without affecting progressive neuronal loss. These treatments often fail to provide sustained clinical benefit and most patients develop motor fluctuations and dyskinesias as the disease progresses. Additionally, non-motor symptoms such as autonomic disturbances, sensory alterations, olfactory dysfunction, mood disorders, sleep disturbances and cognitive impairment cause considerable functional disability in these patients and these features often fail to respond to standard dopaminergic treatments. This mini review outlines the current pharmacotherapeutic options for PD and highlights the emerging experimental therapies in various phases of clinical development.
Topics: Adenosine A2 Receptor Antagonists; Alanine; Animals; Benzylamines; Drug Therapy; Humans; Levodopa; Parkinson Disease
PubMed: 25637088
DOI: 10.1016/j.ejphar.2015.01.030 -
Neurological Sciences : Official... Aug 2020Treatment of Parkinson's disease with levodopa/carbidopa/entacapone (LCE) has been studied for a long time. However, the efficacy and safety of LCE in the treatment of... (Meta-Analysis)
Meta-Analysis Review
Treatment of Parkinson's disease with levodopa/carbidopa/entacapone (LCE) has been studied for a long time. However, the efficacy and safety of LCE in the treatment of early Parkinson's disease (PD) still need to be assessed. Our objective was to do a meta-analysis of relevant randomized controlled trials (RCTs) to evaluate the efficacy and safety of LCE for early PD. PubMed, Embase, the Cochrane Library, and the Web of Science were searched for RCTs with "levodopa/carbidopa/entacapone" and "Parkinson's disease" as keywords. The search period was from inception to October 2018. The quality of included studies was strictly evaluated. We evaluated the quality of included studies strictly and six studies met all inclusion criteria. The results showed that LCE could improve activities of daily living and motor function in PD patients. However, LCE therapy was associated with higher risks of total AEs and single AEs compared with traditional therapy.
Topics: Antiparkinson Agents; Carbidopa; Catechols; Drug Combinations; Humans; Levodopa; Nitriles; Parkinson Disease
PubMed: 32162166
DOI: 10.1007/s10072-020-04303-x -
NeuroImage Apr 2023Humans learn through reinforcement, particularly when outcomes are unexpected. Recent research suggests similar mechanisms drive how we learn to benefit other people,... (Randomized Controlled Trial)
Randomized Controlled Trial
Humans learn through reinforcement, particularly when outcomes are unexpected. Recent research suggests similar mechanisms drive how we learn to benefit other people, that is, how we learn to be prosocial. Yet the neurochemical mechanisms underlying such prosocial computations remain poorly understood. Here, we investigated whether pharmacological manipulation of oxytocin and dopamine influence the neurocomputational mechanisms underlying self-benefitting and prosocial reinforcement learning. Using a double-blind placebo-controlled cross-over design, we administered intranasal oxytocin (24 IU), dopamine precursor l-DOPA (100 mg + 25 mg carbidopa), or placebo over three sessions. Participants performed a probabilistic reinforcement learning task with potential rewards for themselves, another participant, or no one, during functional magnetic resonance imaging. Computational models of reinforcement learning were used to calculate prediction errors (PEs) and learning rates. Participants behavior was best explained by a model with different learning rates for each recipient, but these were unaffected by either drug. On the neural level, however, both drugs blunted PE signaling in the ventral striatum and led to negative signaling of PEs in the anterior mid-cingulate cortex, dorsolateral prefrontal cortex, inferior parietal gyrus, and precentral gyrus, compared to placebo, and regardless of recipient. Oxytocin (versus placebo) administration was additionally associated with opposing tracking of self-benefitting versus prosocial PEs in dorsal anterior cingulate cortex, insula and superior temporal gyrus. These findings suggest that both l-DOPA and oxytocin induce a context-independent shift from positive towards negative tracking of PEs during learning. Moreover, oxytocin may have opposing effects on PE signaling when learning to benefit oneself versus another.
Topics: Humans; Dopamine; Learning; Levodopa; Magnetic Resonance Imaging; Oxytocin; Reinforcement, Psychology; Reward
PubMed: 36848972
DOI: 10.1016/j.neuroimage.2023.119983 -
Journal of Nuclear Medicine : Official... Jul 2021Congenital hyperinsulinism is characterized by persistent hypoglycemia due to inappropriate excess secretion of insulin resulting in hyperinsulinemic hypoglycemia. The...
Congenital hyperinsulinism is characterized by persistent hypoglycemia due to inappropriate excess secretion of insulin resulting in hyperinsulinemic hypoglycemia. The clinical course varies from mild to severe, with a significant risk for brain damage. Imaging plays a valuable role in the care of infants and children with severe hypoglycemia unresponsive to medical therapy. F-6-fluoro-l-dopa PET/CT is the method of choice for the detection and localization of a focal lesion of hyperinsulinism. Surgical resection of a focal lesion can lead to a cure with limited pancreatectomy. This article reviews the role of F-6-fluoro-l-dopa PET/CT in the management of this vulnerable population.
Topics: Congenital Hyperinsulinism; Humans; Infant; Levodopa; Positron Emission Tomography Computed Tomography
PubMed: 34230074
DOI: 10.2967/jnumed.120.246033 -
Neuroscience Research Apr 2022L-3,4-dihydroxyphenylalanine (l-DOPA) is the mainstay treatment for Parkinson's disease, but its effectiveness during early disease is marred by the eventual development...
L-3,4-dihydroxyphenylalanine (l-DOPA) is the mainstay treatment for Parkinson's disease, but its effectiveness during early disease is marred by the eventual development of l-DOPA induced dyskinesia. In hemi-parkinsonian rats, the serotonin type 3 (5-HT) antagonists ondansetron and granisetron alleviated dyskinesia induced by l-DOPA without impeding its anti-parkinsonian action; in parkinsonian marmosets, ondansetron alleviated dyskinesia and enhanced l-DOPA anti-parkinsonian action. Here, we sought to gain insight into the mechanisms governing the anti-dyskinetic action of 5-HT antagonists and measured 5-HT receptor levels across different brain, using [H]GR65630 autoradiographic binding. Brain sections were chosen from 6-hydroxydopamine (6-OHDA)-lesioned rats exhibiting abnormal involuntary movements (AIMs), as well as l-DOPA-naïve 6-OHDA and sham-lesioned animals. [H]GR65630 binding increased in the ipsilateral subthalamic nucleus of 6-OHDA-lesioned rats with mild and severe AIMs, (3-fold changes, P < 0.001). [H]GR65630 binding also increased in the ipsilateral entopeduncular nucleus and thalamus of 6-OHDA-lesioned rats with severe AIMs (75 % and 88 %, P < 0.05). AIMs scores negatively correlated with [H]GR65630 binding in the ipsilateral dorsolateral striatum and contralateral subthalamic nucleus (P < 0.05). These results suggest that alterations in 5-HT mediated neurotransmission may contribute to the pathophysiology of l-DOPA induced dyskinesia.
Topics: Animals; Antiparkinson Agents; Disease Models, Animal; Dyskinesia, Drug-Induced; Levodopa; Ondansetron; Oxidopamine; Rats; Rats, Sprague-Dawley; Serotonin; Subthalamic Nucleus
PubMed: 34954302
DOI: 10.1016/j.neures.2021.12.004 -
ACS Chemical Neuroscience Dec 2014Levodopa was the first and most successful breakthrough in the treatment of Parkinson's disease (PD). It is estimated that PD affects approximately 1 million people in... (Review)
Review
Levodopa was the first and most successful breakthrough in the treatment of Parkinson's disease (PD). It is estimated that PD affects approximately 1 million people in the United States alone. Although PD was discovered in 1817, prior to levodopa's discovery there was not an effective treatment for managing its symptoms. In 1961, Hornykiewicz pioneered the use of levodopa to enhance dopamine levels in the striatum, significantly improving symptoms in many patients. With the addition of carbidopa in 1974, the frequency of gastrointestinal adverse drug reactions (ADRs) was significantly reduced, leading to the modern treatment of PD. Although levodopa treatment is more than 50 years old, it remains the "gold standard" for PD treatment. This Review describes in detail the synthesis, metabolism, pharmacology, ADRs, and importance of levodopa therapy to neuroscience in the past and present.
Topics: Animals; Antiparkinson Agents; History, 19th Century; History, 20th Century; Humans; Levodopa; Neurosciences; Parkinson Disease
PubMed: 25270271
DOI: 10.1021/cn5001759