Search results for: levodopa

Authors: Mahsa Hadipour Jahromy, Sara Rezaii

Abstract:

Parkinson’s disease (PD) results primarily from the death of dopaminergic neurons in the substantia nigra. Soon after the discovery of levodopa and its beneficial effects in chronic administration, debilitating involuntary movements observed, termed levodopa-induced dyskinesia (LID) with poorly understood pathogenesis. Polyphenol-rich compounds, like pomegranate, provided neuroprotection in several animal models of brain diseases. In the present work, we investigated whether pomegranate has preventive effects following 4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic degenerations and the potential to diminish LID in mice. Mice model of PD was induced by MPTP (30 mg/kg daily for five consecutive days). To induce a mice model of LID, valid PD mice were treated with levodopa (50 mg/kg, i.p) for 15 days. Then the effects of chronic co-administration of pomegranate juice (20 ml/kg) with levodopa and continuing for 10 days, evaluated. Behavioural tests were performed in all groups, every other day including: Abnormal involuntary movements (AIMS), forelimb adjusting steps, cylinder, and catatonia tests. Finally, brain tissue sections were prepared to study substantia nigra changes and dopamine neuron density after treatments. With this MPTP regimen, significant movement disorders revealed in AIMS tests and there was a reduction in dopamine striatal density. Levodopa attenuates their loss caused by MPTP, however, in chronic administration, dyskinesia observed in forelimb adjusting step and cylinder tests. Besides, catatonia observed in some cases. Chronic pomegranate co-administration significantly improved LID in both tests and reduced dopaminergic loss in substantia nigra. These data indicate that pomegranate might be a good adjunct for preserving dopaminergic neurons in the substantia nigra and reducing LID in mice.

Keywords: levodopa-induced dyskinesia, MPTP, Parkinson’s disease, pomegranate

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Authors: Jee-Young Lee, Joaquim J. Ferreira, Hyeo-il Ma, José-Francisco Rocha, Beomseok Jeon

Abstract:

The effective management of wearing-off is a key driver of medication changes for patients with Parkinson’s disease (PD) treated with levodopa (L-DOPA). While L-DOPA is well tolerated and efficacious, its clinical utility over time is often limited by the development of complications such as dyskinesia. Still, common first-line option includes adjusting the daily L-DOPA dose followed by adjunctive therapies usually counting for the L-DOPA equivalent daily dose (LEDD). The LEDD conversion formulae are a tool used to compare the equivalence of anti-PD medications. The aim of this work is to compare the effects of opicapone (OPC) 50 mg, a catechol-O-methyltransferase (COMT) inhibitor, and an additional 100 mg dose of L-DOPA in reducing the off time in PD patients with early motor fluctuations receiving different daily L-DOPA doses. OPC was found to be well tolerated and efficacious in advanced PD population. This work utilized patients' home diary data from a 4-week Phase 2 pharmacokinetics clinical study. The Korean ADOPTION study randomized (1:1) patients with PD and early motor fluctuations treated with up to 600 mg of L-DOPA given 3–4 times daily. The main endpoint was change from baseline in off time in the subgroup of patients receiving 300–400 mg/day L-DOPA at baseline plus OPC 50 mg and in the subgroup receiving >300 mg/day L-DOPA at baseline plus an additional dose of L-DOPA 100 mg. Of the 86 patients included in this subgroup analysis, 39 received OPC 50 mg and 47 L-DOPA 100 mg. At baseline, both L-DOPA total daily dose and LEDD were lower in the L-DOPA 300–400 mg/day plus OPC 50 mg group than in the L-DOPA >300 mg/day plus L-DOPA 100 mg. However, at Week 4, LEDD was similar between the two groups. The mean (±standard error) reduction in off time was approximately three-fold greater for the OPC 50 mg than for the L-DOPA 100 mg group, being -63.0 (14.6) minutes for patients treated with L-DOPA 300–400 mg/day plus OPC 50 mg, and -22.1 (9.3) minutes for those receiving L-DOPA >300 mg/day plus L-DOPA 100 mg. In conclusion, despite similar LEDD, OPC demonstrated a significantly greater reduction in off time when compared to an additional 100 mg L-DOPA dose. The effect of OPC appears to be LEDD independent, suggesting that caution should be exercised when employing LEDD to guide treatment decisions as this does not take into account the timing of each dose, onset, duration of therapeutic effect and individual responsiveness. Additionally, OPC could be used for keeping the L-DOPA dose as low as possible for as long as possible to avoid the development of motor complications which are a significant source of disability.

Keywords: opicapone, levodopa, pharmacokinetics, off-time

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Authors: Mohammad Ali Karimi, Hossein Tavallali, Abdolhamid Hatefi-Mehrjardi

Abstract:

In this study, an electrochemical sensor based on gold nanoparticles (AuNPs) functionalized improved graphene (AuNPs-IGE) was fabricated for selective determination of L-dopa in the presence of ascorbic acid by a novel self-assembly method. The AuNP IGE modified carbon paste electrode (AuNPs-IGE/CPE) utilized for investigation of the electrochemical behavior of L-dopa in phosphate buffer solution. Compared to bare CPE, AuNPs-IGE/CPE shows novel properties towards the electrochemical redox of levodopa (L-dopa) in phosphate buffer solution at pH 4.0. The oxidation potential of L-dopa shows a significant decrease at the AuNPs-IGE/CPE. The oxidation current of L-dopa is higher than that of the unmodified CPE. AuNPs-IG/CPE shows excellent electrocatalytic activity for the oxidation of ascorbic acid (AA). Using differential pulse voltammetry (DPV) method, the oxidation current is well linear with L-dopa concentration in the range of 0.4–50 µmol L-1, with a detection limit of about 1.41 nmol L-1 (S/N = 3). Therefore, it was applied to measure L-dopa from real samples that recoveries are 94.6-106.2%. The proposed electrode can also effectively avoid the interference of ascorbic acid, making the proposed sensor suitable for the accurate determination of L-dopa in both pharmaceutical preparations and human body fluids.

Keywords: gold nanoparticles, improved graphene, L-dopa, self-assembly

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Authors: Cameron Wilson, Megan Hanrahan, Katie Brittain, Riona McArdle, Alison Keogh, Lynn Rochester

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Background: The loss of mobility and functional dependence is a significant marker in the progression of neurodegenerative diseases such as Parkinson’s Disease (PD). Pharmacological, surgical, and therapeutic treatments are available that can help in the management and amelioration of PD symptoms; however, these only prolong more severe symptoms. Accordingly, ensuring people with PD can maintain independence and a healthy wellbeing are essential in establishing an effective treatment option for those afflicted. Existing literature reviews have examined experiences in engaging with PD treatment options and the impact of PD on independence and wellbeing. Although, the literature fails to explore the influence of treatment options on independence and wellbeing and therefore misses what people value in their treatment. This review is the first that synthesises the impact of mobility-related treatments on independence and wellbeing in people with PD and their carers, offering recommendations to clinical practice and provides a conceptual framework (in development) for future research and practice. Objectives: To explore the impact of mobility-related treatment (both pharmacological and non-pharmacological) on the independence and wellbeing of people with PD and their carers. To propose a conceptual framework to patients, carers and clinicians which captures the qualities people with PD value as part of their treatment. Methods: We performed a critical interpretive synthesis of qualitative evidence, searching six databases for reports that explored the impact of mobility-related treatments (both drug and non-pharmacological) on independence and wellbeing in Parkinson’s Disease. The types of treatments included medication (Levodopa and Amantadine), dance classes, Deep-Brain Stimulation, aquatic therapies, physical rehabilitation, balance training and foetal transplantation. Data was extracted, and quality was assessed using an adapted version of the NICE Quality Appraisal Tool Appendix H before being synthesised according to the critical interpretive synthesis framework and meta-ethnography process. Results: From 2301 records, 28 were eligible. Experiences and impact of treatment pathway on independence and wellbeing was similar across all types of treatments and are described by five inter-related themes: (i) desire to maintain independence, (ii) treatment as a social experience during and after, (iii) medication to strengthen emotional health, (iv) recognising physical capacity and (v) emphasising the personal journey of Parkinson’s treatments. Conclusion: There is a complex and inter-related experience and effect of PD treatments common across all types of treatment. The proposed conceptual framework (in development) provides patients, carers, and clinicians recommendations to personalise the delivery of PD treatment, thereby potentially improving adherence and effectiveness. This work is vital to disseminate as PD treatment transitions from subjective and clinically captured assessments to a more personalised process supplemented using wearable technology.

Keywords: parkinson's disease, medication, treatment, dance, review, healthcare, delivery, levodopa, social, emotional, psychological, personalised healthcare

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Authors: Sandeep Goyal, Sandeep Saluja

Abstract:

Natural antioxidants have major role in maintenance of health. Green tea extract principally contains epigallocatechin-3-gallate (EGCG), as its abundant antioxidant constituent. Green tea is consumed daily worldwide as antioxidant to combat CNS diseases and has traditional importance also. EGCG has neuroprotective potential in various animal models of Parkinson disease, Alzheimer’s disease etc. but its exact mechanism has not been ruled out. The present study has been designed to investigate the anti-inflammatory, antioxidant and mitochondrial modulating mechanism of neuroprotective effect of epigallocatechin-3-gallate against rodent model of rotenone induced Parkinson’s disease (PD). The behavioural alterations were assessed by using open field test apparatus, Chatilon’s grip strength test apparatus and elevated plus maze for determining the locomotor activity, grip strength and cognition respectively. Biochemically, various parameters to assess oxidative stress, neuroinflammation and neurochemical estimations were performed on rat brain homogenates. A histological examination of rat brain striatum was done to check the neurodegeneration. Epigallocatechin-3-gallate (EGCG) at 10 & 20 mg/kg, were investigated for their neuroprotective potential along with levodopa as a standard agent. Minocycline, a microglial activation inhibitor, was administered alone and in combination with EGCG. EGCG and minocycline produced ameliorative effect against rotenone induced PD like symptoms by significantly reduced behavioral, biochemical and histological alterations. Results of our study reveal the neuroprotective effect of EGCG and minocycline against rotenone induced PD. Results of our study indicate that EGCG exerted neuroprotective effect against rotenone induced PD via its antioxidant, anti-inflammatory and mitochondrial modulating mechanisms and substantiate its previously reported and traditional claims for its use in CNS diseases.

Keywords: antioxidants, neurotoxicity, rotenone, EGCG

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Authors: Cherrie Mae S. Sia, Noel J. Belonguel, Jarungchai Anton S. Vatanagul

Abstract:

Background: Parkinson’s disease (PD) is a chronic progressive, neurodegenerative disorder known for its motor symptoms such as bradykinesia, resting tremor, muscle rigidity, and postural instability. Patients with PD also experience non-motor symptoms (NMS) such as depression, fatigue, and sleep disturbances that are most of the time unrecognized by clinicians. This may be due to the lack of spontaneous reports from the patients or partly because of the lack of systematic questioning from the healthcare professional. There is limited data with regards to these NMS especially that of Filipino patients with PD. Objectives: This study aims to determine the non-motor symptoms of Filipino patients with Parkinson’s disease. Materials and Methods: This is a prospective, cohort study involving thirty-four patients of Filipino-descent diagnosed with PD in three out-patient clinics in Cebu City from April to September 2014. Each patient was interviewed using the Non-Motor Symptom Scale (NMSS). A Cebuano version of the NMSS was also provided for the non-English speaking patients. Interview time was approximately ten to fifteen minutes for each respondent. Results: Of the thirty-four patients with Parkinson’s disease, majority was noted to be males (N=19) and the disease was noted to be more prevalent in patients with a mean age of 62 (SD±9) years old. Hypertension (59%) and diabetes mellitus (29%) were the common co-morbidities in the study population. All patients presented more than one NMS, with insomnia (41.2%), poor memory (23.5%) and depression (14.7%) being the first non-motor symptoms to occur. Symptoms involving mood/cognition (mean=2.21), and attention/memory (mean=2.05) were noted to be the most frequent and of moderate severity. Based on the NMSS, the symptoms that were noted to be mild and often to occur were those that involved the mood/cognition (score=3.84), attention/memory (score=3.50), and sleep/fatigue (score=3.00) domains. Levodopa-Carbidopa, Ropinirole, and Pramipexole were the most frequently used medications in the study population. Conclusion: Non-motor symptoms (NMS) are common in patients with Parkinson’s disease (PD). They appear at the time of diagnosis of PD or even before the motor symptoms manifest. The earliest non-motor symptoms to occur are insomnia, poor memory, and depression. Those pertaining to mood/cognition and attention/memory are the most frequent NMS and they are of moderate severity. Identifying these NMS by doing a questionnaire-guided interview such as the Non-Motor Symptom Scale (NMSS) before they can become more severe and affect the patient’s quality of life is a must for every clinician caring for a PD patient. Early treatment and control of these NMS can then be given, hence, improving the patient’s outcome and prognosis.

Keywords: non motor symptoms, Parkinson's Disease, insomnia, depression

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