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Background/Objectives: People with Parkinson's disease (PwP) face high risks of bacterial infections and septic shock, often requiring inotrope treatment and mechanical ventilation. The impact of levodopa on these critical care interventions remains unclear. Methods: This retrospective cohort study analyzed data from the Taipei Medical University Clinical Research Database to explore the relationship between levodopa prescription, inotrope treatment duration, and mechanical ventilation dependence in PwP who experienced septic shock. PwP aged 45 years and older who required intensive care for septic shock were categorized into levodopa and non-levodopa groups. Results: Outcomes included inotrope treatment duration, mechanical ventilation dependence, and 3-month mortality. Among 243 PwP (116 without levodopa, 127 with levodopa), no significant difference was observed in the duration of mechanical ventilation dependence. However, levodopa prescription was associated with a significantly extended inotrope treatment duration (estimate: 3.43 days, p = 0.027). Additionally, a nonsignificant trend was identified between levodopa prescription and reduced 3-month mortality (adjusted hazard ratio = 0.67, p = 0.068). Conclusions: These findings highlight the complex interplay between Parkinson's disease management and critical care interventions during septic shock. While levodopa may prolong inotrope use, its potential to influence survival outcomes warrants further investigation. [ABSTRACT FROM AUTHOR]

Parkinson’s disease (PD) is the second most common neurodegenerative disease, marked by motor and non-motor symptoms due to dopaminergic neuron loss. In the past three decades, PD prevalence has significantly increased, arousing growing interest in exploring advanced treatment methods, especially for advanced stages of the disease. The advanced stage of PD is characterized by an inadequate response to oral therapy as well as motor fluctuations and dyskinesias. In response to these challenges, invasive therapeutic options such as infusion therapies have been developed, representing a significant advance in treating advanced PD. This review covers currently available infusion therapies used in PD patients. The first infusion therapy used in PD was the apomorphine subcutaneous pump, which has been used for 30 years and effectively reduces motor fluctuations and dyskinesias. Levodopa/carbidopa intestinal gel also reduces “OFF” periods and improves patients’ quality of life, with effectiveness in addressing non-motor symptoms as well. Levodopa/carbidopa/entacapone intestinal gel therapy allows for a similar therapeutic effect with a lower drug dose due to the addition of entacapone. The foslevodopa/ foscarbidopa subcutaneous pump is a newer therapeutic option that achieves the same therapeutic effects without the need for an invasive procedure. Its advantage over enteral pumps is that it does not require an invasive procedure, such as the placement of a tube in the digestive tract. Selecting patients for these therapies requires a detailed assessment of symptoms and response to treatment. Although these treatment methods do not affect the underlying neurodegenerative process, they are crucial in symptom management. [ABSTRACT FROM AUTHOR]

Background and Objectives: Although widely described in Parkinson's disease (PD), peripheral neuropathy (PNP) is scarcely reported in progressive supranuclear palsy (PSP). We aimed to compare the frequency, clinical and electrophysiologic characteristics of PNP in PSP and PD patients. Methods: This cross-sectional study included 23 PSP and 93 PD patients. Demographic data, Movement Disorders Society-Unified Parkinson's Disease Rating Scale-III (MDS-UPDRS-III), Hoehn–Yahr staging, Toronto Clinical Neuropathy Score, nerve conduction study (NCS), and sympathetic skin response (SSR) were recorded. Diagnosing isolated large fiber neuropathy required abnormal NCS. Isolated small fiber neuropathy required clinical findings of pinprick and thermal sensory loss and/or allodynia and/or hyperalgesia with/without impaired SSR, along with normal NCS. Results: PNP was commoner in PSP than PD (65.2% vs. 50.5%, P = 0.21). While a comparable proportion in both groups had clinical neuropathy, NCS abnormalities predominated in PSP (65.2% vs. 39.8%, P = 0.03). All patients had distal symmetrical axonal polyneuropathy. A significantly higher proportion of PSP patients had large fiber involvement (65.21% vs. 39.78%, χ2 = 4.82; P = 0.03) and mixed fiber PNP (60.9% vs. 33.3%, P = 0.01). PSP patients with neuropathy had a significantly shorter disease duration [median (interquartile range {IQR} = 2 (2-3) years vs. 6 (3-9) years, P < 0.001], higher MDS-UPDRS-III score [median (IQR) = 47 (36–54) vs. 34 (28–49), P = 0.049], higher Hoehn–Yahr stage [median (IQR) = 4 (2–5) vs. 3 (1–5), P < 0.001], and shorter duration of levodopa use [median (IQR) = 2 (1-2) years vs. 3.5 (2-5) years, P = 0.006]. NCS parameters were comparable between PSP and PD patients with neuropathy. While PNP in PSP was not associated with any of the clinical variables, a longer disease duration was independently associated with PNP in PD. Conclusions: PNP affected two-thirds of PSP patients and was more prevalent than PD. Both groups had distal symmetrical axonal polyneuropathy, with mixed fiber PNP predominating in PSP. A longer disease duration in PD was associated with PNP. [ABSTRACT FROM AUTHOR]

Background: Williams syndrome (WS; chromosome 7q11.23 deletion) is a rare, multisystemic, neurodevelopmental disorder with variable penetrance and expressivity. Although movement and psychiatric disorders are known to occur in individuals with WS, parkinsonism, dystonia, and treatment-resistant schizoaffective disorder have not been formally described. Methods: We present two unrelated cases of adults with molecularly confirmed WS and typical histories of developmental delays, intellectual/learning disabilities, and treatment-responsive anxiety/mood disorder who developed similar noteworthy neuropsychiatric expressions. We reviewed detailed neuropsychiatric histories, laboratory investigations, neuroimaging, and treatment responses and compared data for the two cases. Results: Both individuals developed treatment-resistant schizoaffective disorder in adulthood requiring multiple trials of antipsychotic treatments. While on clozapine, both patients developed parkinsonism and generalized dystonia with truncal involvement that responded to trials of low-dose levodopa without exacerbating underlying psychotic or affective symptoms. Conclusion: This report illustrates the novel occurrence of levodopa-responsive movement disorders and treatment-resistant schizoaffective disorder in individuals with WS, adding to the expanding neuropsychiatric phenotypes, and highlighting potential shared underlying mechanisms. The observed treatment response suggests that levodopa, in relatively low doses, may be safe and useful in ameliorating presumed antipsychotic-associated parkinsonism and tardive dystonia in WS. [ABSTRACT FROM AUTHOR]

Carbidopa-levodopa is the primary treatment for motor symptoms associated with Parkinson's disease. Medical-surgical nurses need a comprehensive understanding of the various carbidopa/levodopa formulations to provide effective care. Mechanism of action, pharmacokinetics, and available formulations of carbidopa/levodopa are examined. [ABSTRACT FROM AUTHOR]

A challenge to contemporary medicine is still the discovery of an effective and safe therapy for symptomatic control, if not cure, of Parkinson's disease. While the potential century's break-through is sought and foreseen by many scientists in gene therapy, immunotherapy, new drug combinations, and neurosurgical approaches, the not-yet-conventional intranasal administration of "classic" levodopa (L-DOPA) also stands out as a perspective from which Parkinson's patients may benefit in the short term. With the main drawbacks of the standard oral L-DOPA treatment being the extremely low systemic and cerebral bioavailability, it is widely recognized that the nasal route may turn out to be the better administration site, for it offers the alternative of direct brain delivery via the olfactory bulb (the so-called nose-to-brain axis). However, such advancement would be unthinkable without the current progress in nano-scaled drug carriers which are needed to ensure drug stability, mucosal retention and permeation, olfactory uptake, and harmlessness to the sensory neurons and respiratory cilia. This study aims to review the most significant results and achievements in the field of nano-particulate nose-to-brain delivery of L-DOPA. [ABSTRACT FROM AUTHOR]

BACKGROUND: DATATOP was a study of early Parkinsons disease (PD) conducted in the 1980 s, before mandatory folic acid fortification in the United States. Our analysis of its baseline serum samples revealed a geometric mean vitamin B12 of 369 pg/mL and homocysteine (tHcy) of 9.5μmol/l. We also found that low B12 predicted greater worsening of ambulatory capacity (AC) and elevated tHcy (>15μmol/L) predicted greater declines in cognitive function. OBJECTIVE: We sought to measure B12 and tHcy in contemporary trial participants with early PD who had not started dopaminergic treatment and to determine whether these analytes were associated with clinical progression. METHODS: We measured B12 and tHcy from baseline and end-of-study blood samples from three recent clinical trials. RESULTS: Baseline geometric mean B12 levels for these studies ranged from 484- 618 pg/ml and for tHcy ranged from 7.4- 10μmol/L. Use of B12-containing supplements ranged from 41- 61%, and those taking supplements had higher B12 and lower tHcy. Those who began levodopa, but were not taking B12-supplements, had greater end-of-study tHcy. There was no association of baseline tHcy > 15μmol/L with annualized change in Montreal Cognitive Assessment and no association of baseline B12 tertiles with change in AC. CONCLUSIONS: In these longitudinal trials, B12 levels were higher than for DATATOP, due in large part to increased B12-supplement intake, while tHcy levels were similar. Initiation of levodopa was associated with increases of tHcy in those not taking a B12-containing supplement. These smaller studies did not replicate prior findings of low B12 and elevated tHcy with features of progression, possibly due to higher baseline B12.

BackgroundTremor in Parkinson's disease (PD) is commonly seen in the upper extremities and can involve the lower extremities and mouth. We present a case of a patient with idiopathic PD who presented with abdominal tremor.Case reportA 40-year-old man with a 2-year history of subjective weakness and stiffness in the right arm and leg, followed by emergence of a right hand tremor, subsequently developed abdominal tremor. Patient experienced marked improvement of both abdominal and hand tremor and mobility of the right limbs with levodopa.DiscussionOur case report serves as the second only published report of abdominal tremor in an idiopathic PD patient.HighlightsTremor in Parkinson's disease (PD) commonly affects the upper and lower extremities and mouth. We describe a 40-year-old man with PD who developed abdominal tremor which was brought under control with levodopa. This case is one of only two published reports of abdominal tremor in PD.

Introduction. Microparticles are of great interest for use in various drug delivery systems. The intranasal route of administration holds a special place due to its several advantages, including ease of use, minimal side effects, and the ability for rapid delivery of drug directly to the brain. The drug in the microparticles acts locally, thereby ensuring the release of the drug in the required amount in the target organ. The drug from the nose enters directly into the brain through the olfactory region along the sensory nerves. The development of microparticles with the ability to mucoadhesion on the surface of the nasal mucosa will increase the bioavailability of drugs used in the treatment of diseases and disorders of the central nervous system (CNS).Aim. Development and study of microcapsules with mucoadhesive properties for the intranasal delivery system of levodopa.Materials and methods. Microcapsules (MC) were obtained by ultrasonic electrospraying method on a B-390 encapsulator (BUCHI, Switzerland) followed by filtration under vacuum, washing with deionized water and freeze-drying at –50 °C and 0.05 mBar for 48 h in a FreeZone 1 L dryer (Labconco, USA). The structural features of MC were studied by optical microscopy using Evident CX33 microscope with high-resolution camera (Olympus, Japan). For evaluation of the images, we used ImageView™ software (version x64, 4.11.22376.20230402). Morphology of prepared microcapsules were also detected using a portable ultraviolet light source (Jialitte F114, China) by a digital USB microscope (OT-INL40 1000X, China). The mucoadhesive properties of sodium fluoresceinate-loaded MC were studied using isolated sheep nasal mucosa in an SI60 incubator (Stuart, UK) at 37.0 ± 0.5 °C. Fluorescent images were obtained using a TLC Visualizer 3 high-resolution imaging system (CAMAG®, Switzerland). ImageJ 1.53e software (ImageJ, USA) was used to process the obtained macroscopic images and plot graphs. The encapsulation efficiency, % (EE%) and loading capacity, % (LC%) of levodopa loaded MC were assessed using UV spectrophotometry on an Evolution™ 220 device (Thermo Fisher Scientific, USA) at a wavelength of 202 nm. The release of levodopa from MC was performed using a CE 7smart flow cell (SOTAX AG, Switzerland), method IV (State Pharmacopoeia XV of the Russian Federation), at a temperature of 37 ± 0.5 °C for 3 hours in an artificial nasal fluid (ANF) medium. The amount of released drug was determined using an Evolution™ 220 UV spectrophotometer (Thermo Fisher Scientific, USA) at a wavelength of 202 nm.Results and discussion. A method for MC preparation was developed, the device parameters and the optimal composition of microparticles were selected. Two types of MC were obtained: alginate MC and MC coated with Eudragit® EPO (EPO), which have mucoadhesive properties. The average diameter of alginate MC was 0.365 ± 0.018 mm, EPO-coated MC – 0.426 ± 0.017 mm. Alginate MC are washed off the surface of isolated sheep nasal mucosa 5 minutes after irrigation with ANF, and EPO-coated are retained for 1 hour. EE% of MC with levodopa is above 90 %. LC% of EPO-coated is higher than that of alginate MC. The release of levodopa into the ANF medium from EPO-coated MC was 100 % after just 30 minutes of the study, while for alginate MC it was no more than 60 ± 6.1 % after 3 hours.Conclusion. EPO-coated MCs exhibit mucoadhesive properties on the nasal mucosa surface and their further study is promising for use in intranasal levodopa delivery systems.

Abstract Background Geographic atrophy (GA) is a significant cause of vision loss in patients with age-related macular degeneration (AMD). Current treatments are limited to anti-complement drugs, which have limited efficacy to delay progression with significant risk of complications. Levodopa (L-DOPA) is a byproduct of melanin synthesis that is associated with reduced development of neovascular AMD. In this study, we determined if L-DOPA was associated with a reduced likelihood of new-onset GA. Methods We performed a retrospective analysis in the Vestrum Health Retina Database. We included eyes with non-neovascular AMD without GA and 1–5 years of follow-up. Eyes were divided into two groups. Exposed to L-DOPA before or on the date of non-neovascular AMD without GA diagnosis, and eyes not exposed to L-DOPA. We extracted age, sex, AREDS2 status, dry AMD stage, smoking history, and conversion rate to GA at years 1 through 5. Propensity score matching was used to match L-DOPA and control groups. Cox proportional hazard regression, adjusting for age, sex, AMD severity, AREDS2 use, smoking status, and L-DOPA use was employed to calculate hazard ratios for new-onset GA detection. Results We identified 112,089 control and 844 L-DOPA exposed eyes with non-neovascular AMD without GA. After propensity score matching, 2532 control and 844 L-DOPA exposed eyes remained that were well-matched for age, sex, AMD severity, AREDS2 use, and smoking status. We found that L-DOPA exposure was associated with a significantly reduced likelihood (HR = 0.68, 95% CI: 0.48–0.95, P = 0.025) of new-onset GA detection. Conclusion L-DOPA use was associated with reduced detection of new-onset GA.

Abstract A sustainable HPTLC-densitometric method was developed for quantitative determination of Quetiapine (QUET), Levodopa (LD) and Carbidopa (CD) in presence of Dopamine (DOP) as an internal standard. This applicable technique was achieved by spiking human plasma and extraction was performed using the protein precipitation approach. The mobile phase used was acetone, dichloromethane, n-butanol, glacial acetic acid and water (3: 2.5: 2: 2: 1.75, by volume). Method validation was done according to US-FDA guidelines and was able to quantify Quetiapine, Levodopa and Carbidopa in the ranges of 100–4000, 200–8000 and 30–1300 ng/mL, respectively. Bioanalytical method validation parameters were assessed for the studied drugs. Finally, the analytical suggested methodology was evaluated using various green and white analytical chemistry metrics and other tools, such as the green solvent selection tool, analytical eco-scale, green analytical procedure index, analytical greenness metric approach and the red–green–blue algorithm tool. The results revealed that the applied analytical method had a minor impact on the environment and is a relatively greener option than other previously reported chromatographic methods. Graphical Abstract

Since its first introduction, levodopa has remained the cornerstone treatment for Parkinson's disease. However, as the disease advances, the therapeutic window for levodopa narrows, leading to motor complications like fluctuations and dyskinesias. Clinicians face challenges in optimizing daily therapeutic regimens, particularly in advanced stages, due to the lack of quantitative biomarkers for continuous motor monitoring. Biochemical sensing of levodopa offers a promising approach for real-time therapeutic feedback, potentially sustaining an optimal motor state throughout the day. These sensors vary in invasiveness, encompassing techniques like microdialysis, electrochemical non-enzymatic sensing, and enzymatic approaches. Electrochemical sensing, including wearable solutions that utilize reverse iontophoresis and microneedles, is notable for its potential in non-invasive or minimally invasive monitoring. Point-of-care devices and standard electrochemical cells demonstrate superior performance compared to wearable solutions; however, this comes at the cost of wearability. As a result, they are better suited for clinical use. The integration of nanomaterials such as carbon nanotubes, metal–organic frameworks, and graphene has significantly enhanced sensor sensitivity, selectivity, and detection performance. This framework paves the way for accurate, continuous monitoring of levodopa and its metabolites in biofluids such as sweat and interstitial fluid, aiding real-time motor performance assessment in Parkinson's disease. This review highlights recent advancements in biochemical sensing for levodopa and catecholamine monitoring, exploring emerging technologies and their potential role in developing closed-loop therapy for Parkinson's disease. [ABSTRACT FROM AUTHOR]

Aim of this review is to discuss the value of current ongoing research initiatives in Parkinson's disease from the clinicians' point of view. The repeat, recent failures on progress slowing reflect the drifting apart between initially promising experimental and then disappointing clinical outcomes in the translational trials with well selected Parkinson's disease patients. A similar development concerns the emerging gap between novel developed drugs with improved pharmacokinetic behaviour and their limited use in the clinical practice following approval. Restricted regional different worldwide availability and direct, respectively indirect budget limitations for neurologists in private practice are essential hurdles. They prevent the widespread prescription of these compounds. As a result return of investment for the pharmaceutical industry becomes more and more uncertain. The interest for research on novel treatment approaches for the amelioration of motor and non motor symptoms declines. Clinicians crucially scrutinize the claim for an optimum patient care by payers and regulators. [ABSTRACT FROM AUTHOR]

Objectives: To determine the effect of Bilateral Subthalamic Nucleus (STN) Deep Brain Stimulation (DBS) on drug reduction for Parkinson's disease (PD) in a low-middle-income country. Methods: This retrospective cohort study included 49 patients following interview based questionnaires who underwent bilateral STN DBS at the Department of Neurosurgery, Punjab Institute of Neurosciences, Lahore, Pakistan over five years (July 30, 2018 to June 29, 2023). Patients meeting the inclusion and exclusion criteria (49 patients) were selected and the effect of bilateral STN DBS on drug reduction was evaluated. Results: Following bilateral STN for Parkinsons Disease Levodopa equivalent daily dose (LEDD) and Unified Parkinson's Disease Rating Scale (UPDRS)-III results were statistically significant, with a P-value of 0.0001. Effect of DBS on UPDRSIV was 0.2751, which is statistically insignificant. LEDD reduced by 55.03% (P<0.0001), UPRS-III improved by 80.49% (P<0.0001), and UPDRS-IV improved by 1% (P<0.0001). Time spent with dyskinesia reduced by 17.54% (P<0.0001), whereas time spent off period reduced 22.44% (P<0.0001). Conclusion: When the disease is in its early stages and has not yet manifested advanced Parkinsons symptoms, bilateral STN DBS is an effective treatment option. It considerably reduces the need for levodopa and significantly improves the motor symptoms of rigidity, tremors, and bradykinesia. [ABSTRACT FROM AUTHOR]

To systematically evaluate the effectiveness and safety of safinamide in the treatment of levodopa-induced motor complications of Parkinson's disease (PD). A search strategy was developed and PubMed, Embase, Web of Science, Cochrane Library, Chinese BioMedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), and WanFang Data were searched to find randomized controlled trials on the treatment of PD motor complications caused by levodopa with safinamide. A manual reference search was conducted for articles published until June 2022 to independently screen references, extract data, and evaluate the risk of bias in the included studies. RevMan 5.3 software was utilized to analyze the data. A total of 5 randomized controlled trials with 2061 PD patients were included, containing 1277 patients in the safinamide group (trial group) and 784 patients in the control group. Meta-analysis results exhibited that regarding effectiveness, the duration of continuous optimal drug effect without dyskinesia (On-time) of the 50 mg trial group was longer than that of the control group. The On-time of the 100 mg trial group was longer than that of the control group.The improvement of the Unified Parkinson's Disease Rating Scale Part III (UPDRSIII) score in the 50 mg trial group was better than that in the control group. The improvement of the UPDRSIII score of the 100 mg trial group was better than that of the control group.There was no significant difference in the incidence of adverse events between the two groups. Safinamide is effective and safe in the treatment of PD motor complications caused by levodopa. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a common neurodegenerative disease in the older adults. The main pathological change in PD is the degenerative death of dopamine (DA) neurons in the midbrain substantia nigra, which causes a significant decrease in the DA content of the striatum. However, the exact etiology of this pathological change remains unclear. Genetic factors, environmental factors, aging, and oxidative stress may be involved in the degenerative death of dopaminergic neurons in PD. Pharmacological treatment using levodopa (l-DOPA) remains the main treatment for PD. Most patients with PD consuming l-DOPA for a long time usually develop levodopa-induced dyskinesia (LID) after 6.5 years of use, and LID seriously affects the quality of life and increases the risk of disability. Recently, studies have revealed that cerebral iron deposition may be involved in LID development and that iron deposition has neurotoxic effects and accelerates disease onset. However, the relationship between cerebral iron deposition and LID remains unclear. Herein, we reviewed the mechanisms by which iron deposition may be associated with LID development, which are mainly related to oxidative stress, neuroinflammation, and mitochondrial and lysosomal dysfunction. Using iron as an important target, the search and development of safe and effective brain iron scavengers, and thus the alleviation and treatment of LID, has a very important scientific and clinical value, as well as a good application prospect. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) poses a significant therapeutic challenge, mainly due to the limited ability of drugs to cross the blood-brain barrier (BBB) without undergoing metabolic transformations. Levodopa, a key component of dopamine replacement therapy, effectively enhances dopaminergic activity. However, it encounters obstacles from peripheral decarboxylase, hindering its passage through the BBB. Furthermore, levodopa metabolism generates reactive oxygen species (ROS), exacerbating neuronal damage. Systemic pulsatile dosing further disrupts natural physiological buffering mechanisms. In this investigation, we devised a ROS-responsive levodopa prodrug system capable of releasing the drug and reducing ROS levels in the central nervous system. The prodrug was incorporated within second near-infrared region (NIR-II) gold nanorods (AuNRs) and utilized angiopep-2 (ANG) for targeted delivery across the BBB. The processes of tight junction opening and endocytosis facilitated improved levodopa transport. ROS scavenging helped alleviate neuronal oxidative stress, leading to enhanced behavioral outcomes and reduced oxidative stress levels in a mouse model of PD. Following treatment, the PD mouse model exhibited enhanced flexibility, balance, and spontaneous exploratory activity. This approach successfully alleviated the motor impairments associated with the disease model. Consequently, our strategy, utilizing NIR-II AuNRs and ANG-mediated BBB penetration, coupled with the responsive release of levodopa, offers a promising approach for dopamine supplementation and microenvironmental regulation. This system holds substantial potential as an efficient platform for delivering neuroprotective drugs and advancing PD therapy. [ABSTRACT FROM AUTHOR]

Background: Oral levodopa remains the mainstay of treatment for Parkinson's disease (PD). However, as PD progresses, response to treatment may fluctuate. Managing fluctuations can be demanding for clinicians and patients. There is a paucity of real-world studies reporting on PD management in patients with fluctuations in treatment response, especially in patients with advanced stages of PD. The multicentre, observational Parkinson's Disease Fluctuations treatment PAthway (PD-FPA) study describes the real-life management of response fluctuations in Italian patients with advanced PD. Patients and Methods: PD-FPA had a retrospective and prospective phase; herein, retrospective results are presented. Ten Italian centres enrolled patients with a PD diagnosis from 10-15 years prior to study entry (T0) and who had ≥2-year history of fluctuations. Data on patient demographics, medical history, PD stage, fluctuation characteristics, symptoms, and prescribed treatments were collected at T0 and retrospectively (2 years prior to T0) via patient chart review/interview. Results: Overall, 296 patients (60% male, mean age 68 years, 84% with Hoehn and Yahr scores 2-3) were enrolled. At T0, most patients (99.3%) were on oral levodopa therapy. All patients used dopaminergic medications; adjunctive medications included dopamine agonists (56%) and monoamine oxidase B (60%) and catechol-O-methyltransferase enzyme inhibitors (41%). At T0, 51% of patients had changed therapy, with response fluctuations being the most common reason (74%); wearing-off was the most common fluctuation (83%). Conclusion: This interim analysis of PD-FPA suggests that adequate levodopa dosing and adjunctive medications can stabilize advanced PD and provide patients with a good quality of life. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusions Tremor in Parkinson's disease (PD) is commonly regarded as less responsive to levodopa than bradykinesia and rigidity, with levodopa‐resistant PD tremor considered relatively common.The aim was to assess the levodopa responsiveness of tremor, bradykinesia, and rigidity in a population with advanced PD.We performed a retrospective study of 526 people with PD screened for deep brain stimulation.Levodopa's Cohen's d effect sizes were in the same order of magnitude for the 3 cardinal motor symptoms. Proportional improvement in tremor (86.8%) was higher than bradykinesia (45.7%) and rigidity (67.0%) (P < 0.0001). Full resolution was more frequent for tremor (67.9%) than for bradykinesia (0.4%) or rigidity (24.8%) (P < 0.0001). Levodopa‐unresponsive tremor, defined as improvement less than 25%, was documented only in 4.0%, as opposed to 19.4% for bradykinesia and 9.8% for rigidity (P < 0.0001).In advanced PD, tremor was more responsive to levodopa than bradykinesia and rigidity, and levodopa‐unresponsive tremor was relatively rare. [ABSTRACT FROM AUTHOR]

Background: The search for neuroprotective treatments for Parkinson's disease (PD) still relies largely on motor disability scales. A limitation of these tools is the strong influence of symptomatic dopaminergic treatment effects. Drawing on a wealth of published information, we conducted a systematic review and meta-analysis of motor progression in PD and its relationships with dopaminergic therapy. Methods: We searched Medline, Embase, and Central to identify 84 publications with adequate serial motor scores to calculate progression, expressed as an increase in the percentage of maximum disability. Results: A random-effects model showed motor progression at 2.0% p.a. (95% CI 1.7–2.4%). There were no significant differences by baseline age, sample size, or observation period. However, untreated patients, in 8 publications, progressed at 4.5% p.a. compared to 1.6% p.a. in 76 studies containing individuals on dopaminergic drugs (p = 0.0004, q = 0.003). This was supported by research on phenoconversion in prodromal PD, where motor progression exceeded 5% p.a. in the 2 years before diagnosis. Starting levodopa improved pre-treatment disability by 40.3 ± 15.2%. Practically defined off state measurements increase faster than on scores by a modest degree (p = 0.05). Conclusion: This survey suggests that accurate long-term measurements of motor progression to assess disease-modifying therapies can be conducted despite the sequential commencement of dopaminergic drugs and sample attrition over time. While study designs involving prodromal or untreated PD avoid confounding effects of symptomatic treatment, different assumptions about motor progression may be needed. A defined off state with the levodopa test dose method maximizes information about the medication cycle once dopaminergic therapy has begun. [ABSTRACT FROM AUTHOR]

Our language affects patients' perceptions of therapies. In Parkinson's disease, emergent response fluctuations and dyskinesias typically trigger conversations around commencing an "Advanced Therapy" which carries notions of Advanced Disease. The patient, resolute in their commitment to fighting the disease, is misled. Chasing reassurance that their disease has not yet progressed considerably; they may therefore resist a potentially life-changing therapy. Instead, we should offer a "Smart Therapy". This term more accurately and positively describes therapies on offer that stabilize response fluctuations and improve quality of life, without a focus on the negative connotations of progression to more advanced disease. Plain Language Summary: The language we use with our patients affects their perception of a therapy on offer and their willingness to take it up. In Parkinson's disease when motor response fluctuations and dyskinesias become extremely challenging and disabling for patients despite medication optimization, it might prompt conversations with the patient in appropriate circumstances about offering an "Advanced Therapy" such as deep brain stimulation surgery or continuous infusion pumps. However, from the patient's perspective, putting up a steadfast fight against their disease, this label carries unwanted and misleading connotations of Advanced Disease. This can lead to hesitation from taking up these potentially life-changing therapies. Therefore, in this Commentary we propose a rebranding in line with other modern technology like smart phones and smart homes, emphasizing the positive and personalized features of these therapies, and focusing on the goal of stabilizing symptoms and improving quality of life. We should offer patients "Smart Therapies". It's time to Get Smart! [ABSTRACT FROM AUTHOR]

Levodopa is the most widely used medication for the symptomatic treatment of Parkinson's disease and, despite being an "old" drug, is still considered the gold standard for offering symptomatic relief. The pharmacokinetic and pharmacodynamics of levodopa have been studied extensively. Our review explores the molecular mechanisms that affect the absorption of this drug, focusing on the large intra- and interindividual variability of absorption that is commonly encountered in daily clinical practice, and on the interaction with other medications. In addition, we will explore the clinical implications of levodopa absorption variability and address current and future strategies for researchers and clinicians. [ABSTRACT FROM AUTHOR]

A stability-indicating reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed to determine organic impurities in a combination drug containing levodopa and benserazide, frequently used in the treatment of Parkinson's disease. The determination of impurities holds significant importance in combination products, as their higher occurrence impacts both the quality and bio-efficacy of the drug products. Thus, the current RP-HPLC method aims to identify organic impurities, providing simplicity, effectiveness, and reproducibility. A Zorbax SB C18 column (4.6 × 250 mm, 5 μm) was utilized, with a flow rate of 1.0 mL/min and a detection wavelength of 220 nm. The analysis was conducted in isocratic mode with an ambient (25°C) column temperature and a 5°C autosampler temperature. Further, enhanced peak resolution was achieved by employing an iron pair agent. All impurities were effectively separated, and peak purity analysis confirmed the absence of interference for levodopa and benserazide. Accuracy, precision, and linearity were well within acceptable criteria, with the method signifying a correlation coefficient above 0.995 for known impurities of levodopa and benserazide. The method validation, following ICH quality guidelines, exhibited the specificity of the developed method, while the robustness study confirmed its reliability under diverse conditions. Thus, mutual results indicate the pragmatism and applicability of the developed method, reinforcing safe and efficacious therapeutics for patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Parkinson's disease (PD) is one of the most common chronic, degenerative brain diseases worldwide. Patients are diagnosed on the basis of slowness of movement and/or tremor and/or stiffness. However, many symptoms that are not movement related are now well recognized. Patients show changes in skin sensation, and the vast majority of patients show loss of sensory neurites, which enable sensation in skin. These changes in skin sensation occur prior to diagnosis; however, sensory issues may also be exacerbated by levodopa, an important drug used in the treatment of PD. Undoubtedly, levodopa is critical for the treatment of PD, but at high doses, it has repeatedly been shown to impair sensation in PD patients. Here, we show for the first time that high-dose levodopa impairs function of sensory neurons. Importantly, we also show for the first time that lysosomes, a critical organelle involved in recycling, are impaired by levodopa concentrations observed in patients. These data are important given the well-known lysosomal dysfunction observed in PD. Our data shed light on how levodopa, the most important drug in the treatment of PD, may contribute to sensory deficits in PD. Parkinson's disease (PD) is the second-most common neurodegenerative disease worldwide. Patients are diagnosed based upon movement disorders, including bradykinesia, tremor and stiffness of movement. However, non-motor signs, including constipation, rapid eye movement sleep behavior disorder, smell deficits and pain are well recognized. Peripheral neuropathy is also increasingly recognized, as the vast majority of patients show reduced intraepidermal nerve fibers, and sensory nerve conduction and sensory function is also impaired. Many case studies in the literature show that high-dose levodopa may induce or exacerbate neuropathy in PD, which is thought to involve levodopa's metabolism to homocysteine. Here, we treated primary cultures of dorsal root ganglia and a sensory neuronal cell line with levodopa to examine effects on cell morphology, mitochondrial content and physiology, and lysosomal function. High-dose levodopa reduced mitochondrial membrane potential. At concentrations observed in the patient, levodopa enhanced immunoreactivity to beta III tubulin. Critically, levodopa reduced lysosomal content and also reduced the proportion of lysosomes that were acidic, thereby impairing their function, whereas homocysteine tended to increase lysosome content. Levodopa is a critically important drug for the treatment of PD. However, our data suggest that at concentrations observed in the patient, it has deleterious effects on sensory neurons that are not related to homocysteine. [ABSTRACT FROM AUTHOR]

This study presents a novel sensor for the detection of levodopa (LD) utilizing a glassy carbon electrode modified with a TiO2/MWCNT nanocomposite. Structural analysis confirmed the suitability of the nanocomposite for sensor fabrication, revealing enhancements in effective surface area and sensitivity. Characterization studies employing SEM, EDX, and FT-IR analyses provided insights into the composition and morphology of the modified electrode. The sensor exhibited exceptional performance metrics, including a wide linear detection range (19.6–545 µM), low detection limit (2.51 µM), high repeatability (78.1%), and remarkable average recovery rates in real samples (99.86%). Minimal interference from interfering species further demonstrated its practical utility. Moreover, the sensor's direct applicability in diverse sample matrices, without the need for sample separation, highlighted its versatility and convenience. Comparative analysis revealed the sensor's performance to be comparable to established methods, offering a cost-effective and streamlined approach to LD measurement. Overall, the modified glassy carbon electrode with TiO2/MWCNT nanocomposite presents a clear, suitable, and stable electrocatalytic response, promising significant advancements in biosensing technology for LD detection. [ABSTRACT FROM AUTHOR]

A sustainable HPTLC-densitometric method was developed for quantitative determination of Quetiapine (QUET), Levodopa (LD) and Carbidopa (CD) in presence of Dopamine (DOP) as an internal standard. This applicable technique was achieved by spiking human plasma and extraction was performed using the protein precipitation approach. The mobile phase used was acetone, dichloromethane, n-butanol, glacial acetic acid and water (3: 2.5: 2: 2: 1.75, by volume). Method validation was done according to US-FDA guidelines and was able to quantify Quetiapine, Levodopa and Carbidopa in the ranges of 100–4000, 200–8000 and 30–1300 ng/mL, respectively. Bioanalytical method validation parameters were assessed for the studied drugs. Finally, the analytical suggested methodology was evaluated using various green and white analytical chemistry metrics and other tools, such as the green solvent selection tool, analytical eco-scale, green analytical procedure index, analytical greenness metric approach and the red–green–blue algorithm tool. The results revealed that the applied analytical method had a minor impact on the environment and is a relatively greener option than other previously reported chromatographic methods. [ABSTRACT FROM AUTHOR]

Background/Aim. The etiology of polyneuropathy (PNP) in patients with Parkinson's disease (PD) is unclear, and there is a possible association between levodopa therapy, hyperhomocysteinemia, and PNP development due to methylation processes involving vitamin B12 and folic acid. The aim of this study was to analyze the difference in clinical presentation and disease severity between PD patients with and without PNP and to evaluate blood levels of vitamin B12, homocysteine, and folic acid in these patients. Methods. This cross-sectional study included 200 consecutive patients diagnosed with PD, divided into two groups: those with PNP and those without PNP. Diagnosis of PNP was confirmed by electromyoneurography. The first group consisted of 50 patients with PD with confirmed PNP, and the second 50 patients with PD without PNP. All patients were receiving levodopa therapy. Laboratory tests analyzed vitamin B12, folic acid, and homocysteine levels. Results. Patients with PNP were older when PNP was diagnosed (71 vs. 66 years, p < 0.0001), without differences in duration of levodopa therapy (p = 0.359) or daily dose (p = 0.442), and with significant motor impairment according to Unified Parkinson's Disease Rating Scale III (p = 0.017). No difference was found between groups for vitamin B12 (p = 1.0), folic acid (p = 0.124), and homocysteine (p = 0.313) serum levels. Conclusion. PD patients with PNP have a more pronounced motor deficit, while differences in vitamin B12, homocysteine, and folic acid values compared to the group without PNP were not registered. [ABSTRACT FROM AUTHOR]

Background: There has been a long debate whether delaying treatment with levodopa prevents motor complications in Parkinson's disease (PD). Objectives: We performed a meta‐analysis on randomized clinical trials (RCTs) that compared early‐ versus delayed‐start treatment with levodopa in PD. Methods: A systematic review was conducted in PubMed, EMBASE, and Web of Science databases from inception to July 1, 2023. Only RCTs that compared early and delayed levodopa treatment in PD were included. Non‐randomized comparisons from follow‐up studies were included as well. Our primary outcomes were occurrence of overall motor complications, motor fluctuations, and dyskinesias. Results: Seven studies with a total of 1149 patients (636 in the early‐start group and 513 in the delayed‐start) were included in our analysis. There was no difference between groups regarding motor complications (OR 1.39; 95% CI: 0.68–1.72; P = 0.37) or dyskinesias (OR 1.52; 95% CI: 0.90–2.57; P = 0.11). Motor fluctuations occurred less frequently in the early‐start group (OR 0.70; 95% CI: 0.52–0.95; P = 0.02). Nonetheless, on subgroup analysis of dopamine agonists, rate of dyskinesias was smaller in the delayed‐start group (OR 1.82; 95% CI: 1.08–3.07; P = 0.03). Conclusions: Delaying treatment with levodopa does not seem to prevent levodopa‐related motor complications in PD. Adjunct treatment with dopamine agonists may reduce the need for higher doses of levodopa and thus reduce the risk for dyskinesias but this practice is often associated with a higher frequency of adverse effects related to dopamine agonists. [ABSTRACT FROM AUTHOR]

Background: The ideal timing for initiating levodopa in newly diagnosed people with Parkinson's disease (PD) is uncertain due to limited data on the long‐term effects of levodopa. Objective: The aim was to investigate whether early levodopa initiation postpones mortality (primary outcome), the requirement of device‐aided therapies, and the incidence of PD‐related complications, such as fall‐induced injuries. Methods: Using nationwide claims data from Dutch hospitals (2012–2020), we grouped newly diagnosed PD individuals as "early initiators" (initiating levodopa within 2 years of diagnosis) or "nonearly initiators." We used the national death registry to assess mortality and health‐care claims to assess PD‐related complications and device‐aided therapies. We used marginal structural models to compare mortality and device‐aided therapy rates between groups, and a Poisson regression model to compare PD‐related complication rates. Results: Among 29,943 newly diagnosed PD individuals (mean age at diagnosis: 71.6, 38.5% female), there were 24,847 early and 5096 nonearly levodopa initiators. Over a median 4.25 years, 8109 (27.1%) died. The causal risk ratio for mortality was 1.04 (95% confidence interval [CI] 0.92–1.19) for early versus nonearly initiators. The risk ratio of receiving any device‐aided therapy was 3.19 (95% CI 2.56–5.80). No association was observed with incidence of PD‐related complications (incidence rate ratio: 1.00, 95% CI 0.96–1.05). Conclusions: Early levodopa initiation in PD does neither postpone nor accelerate mortality or PD‐related complications, nor does it precipitate earlier occurrence of PD‐related complications or mortality. However, we cannot exclude that the results were influenced by residual confounding due to unmeasured risk factors of mortality. [ABSTRACT FROM AUTHOR]

Rapid control of the content of Parkinson's drugs in biological fluids and pharmaceutical formulations is of great importance because changes in the concentration of these drugs affect their bioavailability and biopharmaceutical properties. Therefore, we presented a simple and convenient method for the ratiometric detection of carbidopa and levodopa for carbon dots (CDs) dual‐fluorescent emission. Dual‐emission CDs were prepared from chitosan using a microwave method, following which the surface was chemically modified with terephthalaldehyde. CDs had two strong well‐separated peaks at 445 and 510 nm. The relative measurement of carbidopa and levodopa was based on the static extinction of CDs at 445 nm and increase at 510 nm, respectively. The linear range for carbidopa measurement was 2.5–300 nM, with a limit of detection (LOD) of 2.1 nM, and a relative standard deviation (RSD) of 1.68%. Further, the linear range for levodopa measurement was equal to 3.0–400 nM, with LOD and RSD% of 2.8 nM and 3.5%, respectively. Also, selectivity of ratiometric sensor in the presence of interferences was investigated, which showed that the recovery of carbidopa and levodopa in serum and urine samples has changed between 96.80% and 116.24% with RSD% 0.11–0.77. CDs also provided good results for the determination of carbidopa and levodopa in real samples, and had high selectivity in the presence of possible interferences. [ABSTRACT FROM AUTHOR]

Background: The wearing-off phenomenon is a key driver of medication change for patients with Parkinson's disease (PD) treated with levodopa. Common first-line options include increasing the levodopa dose or adding a catechol-O-methyltransferase (COMT) inhibitor, but there are no trials comparing the efficacy of these approaches. We evaluated the effectiveness of adjunct opicapone versus an additional 100 mg levodopa dose in PD patients with early wearing-off using pooled data from 2 randomized studies. Methods: The ADOPTION study program included two similarly designed 4-week, open-label studies conducted in South Korea (NCT04821687) and Europe (NCT04990284). Patients with PD, treated with 3–4 daily doses of levodopa therapy and with signs of early wearing-off were randomized (1:1) to adjunct opicapone 50 mg or an additional dose of levodopa 100 mg. Patient-level data from the two studies were pooled. Results: The adjusted mean [SE] change from baseline to week 4 in absolute OFF time (key endpoint) was − 62.8 min [8.8] in the opicapone group and − 33.8 min [9.0] in the levodopa 100 mg group, the difference significantly favoring opicapone (− 29.0 [− 53.8, − 4.2] min, p = 0.02). Significant differences in the Movement Disorder Society—Unified Parkinson's Disease Rating Scale Part III subscore (− 4.1 with opicapone vs − 2.5 with levodopa 100 mg), also favored opicapone (− 1.7 [− 3.3, − 0.04], p < 0.05). Dyskinesia was the most frequently reported adverse event (opicapone 7.2% vs. levodopa 100 mg 4.2%). Conclusions: In these short-term trials, introducing adjunct opicapone was more effective at reducing OFF time than adding another 100 mg levodopa dose in PD patients with early signs of wearing-off. [ABSTRACT FROM AUTHOR]

Advanced Parkinson´s disease (PD) is often complicated by fluctuations of disability depending on plasma levels of levodopa. For most patients OFF phases with worsening of tremor and immobility, but also pain, depression, autonomic symptoms are troublesome. While adjustments of levodopa administrations can relief such fluctuations for some time, "on demand" therapies become more and more important. These "on demand" therapies should provide fast and efficacious relief. During the past years, new options for on demand therapies in PD-associated OFF episodes have been developed, including new formulations of levodopa and apomorphine to provide fast and readily accessible on demand treatment. In this narrative review, the challenges of the treatment of PD-associated fluctuations and OFF states are addressed, with a special focus on sublingual apomorphine (SL-APO) including the results from recent clinical trials. [ABSTRACT FROM AUTHOR]

Learning and memory mainly rely on correct synaptic function in the hippocampus and other brain regions. In Parkinsons disease, subtle cognitive deficits may even precede motor signs early in the disease. Hence, we set out to unravel the earliest hippocampal synaptic alterations associated with human α-synuclein overexpression prior to and soon after the appearance of cognitive deficits in a parkinsonism model. We bilaterally injected adeno-associated viral vectors encoding A53T-mutated human α-synuclein into the substantia nigra of rats, and evaluated them 1, 2, 4 and 16 weeks post-inoculation by immunohistochemistry and immunofluorescence to study degeneration and distribution of α-synuclein in the midbrain and hippocampus. The object location test was used to evaluate hippocampal-dependent memory. Sequential window acquisition of all theoretical mass spectrometry-based proteomics and fluorescence analysis of single-synapse long-term potentiation were used to study alterations to protein composition and plasticity in isolated hippocampal synapses. The effect of L-DOPA and pramipexole on long-term potentiation was also tested. Human α-synuclein was found within dopaminergic and glutamatergic neurons of the ventral tegmental area, and in dopaminergic, glutamatergic and GABAergic axon terminals in the hippocampus from 1 week post-inoculation, concomitant with mild dopaminergic degeneration in the ventral tegmental area. In the hippocampus, differential expression of proteins involved in synaptic vesicle cycling, neurotransmitter release and receptor trafficking, together with impaired long-term potentiation were the first events observed (1 week post-inoculation), preceding cognitive deficits (4 weeks post-inoculation). Later on, at 16 weeks post-inoculation, there was a deregulation of proteins involved in synaptic function, particularly those involved in the regulation of membrane potential, ion balance and receptor signalling. Hippocampal long-term potentiation was impaired before and soon after the onset of cognitive deficits, at 1 and 4 weeks post-inoculation, respectively. L-DOPA recovered hippocampal long-term potentiation more efficiently at 4 weeks post-inoculation than pramipexole, which partially rescued it at both time points. Overall, we found impaired synaptic plasticity and proteome dysregulation at hippocampal terminals to be the first events that contribute to the development of cognitive deficits in experimental parkinsonism. Our results not only point to dopaminergic but also to glutamatergic and GABAergic dysfunction, highlighting the relevance of the three neurotransmitter systems in the ventral tegmental area-hippocampus interaction from the earliest stages of parkinsonism. The proteins identified in the current work may constitute potential biomarkers of early synaptic damage in the hippocampus and hence, therapies targeting these could potentially restore early synaptic malfunction and consequently, cognitive deficits in Parkinsons disease.

IntroductionLevodopa (L-3,4-dihydroxyphenylalanine)g, a dopamine precursor that circulates in the peripheral region, is involved in pancreatic glycemic control. Although previous animal studies have shown that peripheral levodopa is correlated with insulin secretion in pancreatic beta cells, the mechanism by which the pancreas uses levodopa differently in humans with obesity and type 2 diabetes remains unknown. Our study aimed to observe how the pancreas uptakes and utilizes levodopa differently under obese and diabetic conditions.Materials and method18F-fluoro-L-dopa positron emission tomography-computed tomography (18F-FDOPA PET-CT) was used to visualize how the human body uses levodopa under obese and diabetic conditions and presented its clinical implications. 10 patients were divided into 3 groups: 1) Group A, normal weight without type 2 diabetes; 2) Group B, obese without type 2 diabetes; and 3) Group C, obese with new-onset type 2 diabetes. All patients’ lifestyle modification was conducted prior to 18F-FDOPA PET-CT, and plasma samples were collected to confirm changes in amino acid metabolites.ResultsPancreatic levodopa uptake increased in obese patients with insulin resistance, whereas it decreased in obese patients with new-onset type 2 diabetes [standardized uptake value (SUV) mean in participants with normal weight, 2.6 ± 0.7; SUVmean in patients with obesity, 3.6 ± 0.1; SUVmean in patients with obesity and new-onset type 2 diabetes, 2.6 ± 0.1, P = 0.02].ConclusionsThis suggested that the alterations in the functional capacity of pancreatic beta cells to take up circulating levodopa are potentially linked to the insulin resistance and the pathogenesis of type 2 diabetes. The differences in the uptake values between the groups implied that pancreatic levodopa uptake could be an early indicator of type 2 diabetes.

BackgroundAntiparkinsonian medication has significantly evolved over the last 2 decades, offering various pharmacologic approaches. The aim of this study was to explore the trends and to determine the statistical significance of the observed changes in the antiparkinsonian medication utilization in Romania during 1998–2022.MethodsThis antiparkinsonian drug utilization study used data provided by CEGEDIM Romania, originating from the Pharma and Hospital Report. Quantitative data for each ATC N04 antiparkinsonian medication were converted to total defined daily doses (DDDs) and to DDD/1000inhabitants/day (DDD/TID). The autoregressive integrated moving average (ARIMA) model was employed to determine the statistical significance of the observed changes in the trends of antiparkinsonian drug use.ResultsThe utilization of antiparkinsonian medication increased considerably (6-folds) in Romania during the 25 years, from 1.03 DDD/TID in 1998 to 6.22 DDD/TID in 2022. Starting 2005, dopamine precursor (levodopa) became the most used antiparkinsonian drug and remained on this position until the end of the study (13-fold increase from 0.17 in 1998 to 2.30 DDD/TID in 2022). MAO-B inhibitors represented the second most used antiparkinsonian drug class for the majority of the years. Selegiline was the most used until 2017 (0.82 DDD/TID), when a decrease in use was observed and continued until 2022 (0.49 DDD/TID). Utilization of dopamine agonists started in 1999, with less than 0.01 DDD/TID, and increased to 1.47 DDD/TID in 2022. Ropinirole was the most used dopamine agonist (0.56 DDD/TID in 2022). Anticholinergic agents represented the most used antiparkinsonian drugs until 2005. Trihexyphenidyl was the main anticholinergic prescribed with a maximum utilization of 0.82 DDD/TID in 2000 followed by a slight decrease until 2022 (0.56 DDD/TID). Amantadine utilization was mainly constant throughout the 25 years, with 0.32 DDD/TID prescribed in 2022. ARIMA analysis showed that the changes in antiparkinsonian drugs consumption were not statistically significant and overall, the trend for antiparkinsonian drug use demonstrates an upward trajectory.ConclusionAntiparkinsonian medication showed an increasing utilization trend in Romania during 1998–2022. Levodopa was the most used antiparkinsonian medicine after 2005, replacing anticholinergic agents. MAO-inhibitors utilization came in second and was followed by dopamine agonists. Observing the trend in antiparkinsonian medication utilization over time is essential for providing insights into their real-world use and uptake in a large population.