Antiparkinsonian Drugs Research Articles

Adherence to Medication among Parkinson's Disease Patients Using the Adherence to Refills and Medications Scale.

Objectives Adherence to medication is an important factor that can influence Parkinson's disease (PD) control. We aimed to explore patients' adherence to antiparkinsonian medication and determine factors that might affect adherence to medications among PD patients. Methods A cross-sectional, exploratory survey of PD patients treated with at least one antiparkinsonian drug and with a total score of MoCA (Montreal Cognitive Assessment) ≥26 was conducted. The final sample included 112 PD patients. A patient's adherence was assessed through ARMS (Adherence to Refills and Medications Scale). ARMS scores higher than 12 were assumed lower adherence. In addition, each patient underwent neurological examination, assessment of depression, anxiety, and evaluation of the presence of PD nonmotor symptoms. Results The mean ARDS value in our cohort was 14.9 ± 2.5. Most PD patients (74.1%) reported lower adherence to their medication. Participants in the lower adherence group were younger at PD onset, had significantly higher UPDRS (Unified PD Rating Scale) scores, as well as UPDRS III and UPDRS IV subscores, HARS (Hamilton Anxiety Rating Scale), and NMSQuest (Non-Motor Symptoms Questionnaire for PD) scores compared to the fully adherent group (p=0.013, p=0.017, p=0.041, p=0.043, and p=0.023, respectively). Among nonmotor PD symptoms, the presence of cardiovascular, apathy/attention-deficit/memory disorders, hallucinations/delusions, and problems regarding changes in weight, diplopia, or sweating were associated with lower adherence. Multivariate regression analysis revealed depression as the strongest independent predictor of lower adherence. Conclusion Depressed PD patients compared to PD patients without clinical depression had a three times higher risk for lower adherence to pharmacotherapy. Recognition and adequate treatment of depression might result in improved adherence.

Exploring Unmet Information Needs of People with Parkinson's Disease and Their Families: Focusing on Information Sharing in an Online Patient Community.

This study aimed to examine the unmet information needs of people with Parkinson’s disease and their family members by analyzing Parkinson’s disease-related posts in online communities. Data were collected from one of the largest online people with Parkinson’s disease communities used in South Korea. The word cloud, the main questions from the free-posting messages, as well as the frequently asked symptoms and side effects of the medication, were analyzed using content analysis. The commonly mentioned main questions from the free-posting messages have pertained to treatment-related information, such as effects and side effects of medication, deep brain stimulation, and complementary and alternative medicine. People with Parkinson’s disease and their families depend not only on health care providers but also on using online communities to find the information that they need. However, there is a need for treatment-specific information, such as anti-Parkinson drugs, deep brain stimulation, and complementary alternative therapies. As for the method of providing information for people with Parkinson’s disease and their families, it will be effective to provide tailored education services using online communities and social media by using their information needs and preferred resources.

Evaluation of the effect of the neurotoxin MPTP and the antiparkinsonian drug hemantane on the DNA integrity in the brain structures of C57BL/6 mice

Hemantane (N-adamant-2-yl-hexamethylenimine hydrochloride) is an antiparkinsonian drug with a multicomponent mechanism of action, including a modulating effect on the activity of dopamine and serotonergic mediator systems, a selective inhibitory effect on MAO-B, properties of a low-affinity non-competitive channel blocker of glutamate NMDA receptors, has moderate antiradical and anti-inflammatory activity. The aim of this study was to assess the effect of the neurotoxin MPTP, which is used for modeling of parkinsonian syndrome, and the hemantane on the DNA integrity in the striatum and frontal cortex of the brain of C57BL/6 mice by the DNA comet assay – gel electrophoresis of DNA single cells. Results. In the first experiment, hemantane was administered once a day for 5 days before the MPTP (20 mg/kg, i.p.), then together with MPTP once a day for 5 days. In the second experiment hemantane 10 mg/kg was injected preliminarily for 4 days and 40 minutes before MPTP 30 mg/kg. The obtained results confirm the absence of an effect on DNA of hemantane at a therapeutic dose of 10 mg / kg. In the experimental schemes used, we did not reveal the expected increase in the level of DNA damage under the influence of MPTP, and, accordingly, we were not able to assess the protective effect of hemantane.

Antiparkinsonian Drug Reduction After Directional Versus Omnidirectional Bilateral Subthalamic Deep Brain Stimulation

BackgroundSeveral pilot trials and the Clinical Evaluation of the Infinity Deep Brain Stimulation System (PROGRESS) study have found that directional stimulation can provide a wider therapeutic window and lower therapeutic current strength than omnidirectional stimulation. ObjectiveWe conducted a single-center, open-label, registry-based, comparative trial to test the hypothesis that directional stimulation can be associated with a greater reduction in the total daily dose of antiparkinsonian medications (ApMeds) than omnidirectional stimulation. Materials and MethodsA total of 52 patients with directional and 57 subjects with omnidirectional bilateral subthalamic deep brain stimulation (STN-DBS) were enrolled. Preoperatively and 12 months postoperatively, the dose of different ApMeds, the number of tablets used daily, the severity of motor and nonmotor symptoms using the Movement Disorder Society–sponsored Unified Parkinson Disease Rating Scale, and the health-related quality of life (HRQoL) using the 39-item Parkinson’s Disease Questionnaire (PDQ-39) were assessed. ResultsAccording to the changes in the levodopa equivalent daily dose, directional STN-DBS led to a 13% greater reduction in the total daily dose of ApMed. The 10.3% greater reduction in the dose of levodopa was the main contributor to this difference. The number of different ApMed types also could be decreased in a greater manner with directional stimulation. The improvement in the severity of motor and nonmotor symptoms was comparable; however, we detected a 15.8% greater improvement in the global HRQoL among patients with directional stimulation according to the changes in the summary index of the PDQ-39. The total electrical energy delivered per second was comparable between the groups at 12-month postoperative visit, whereas the amplitude of stimulation was significantly lower and the impedance was significantly higher with directional leads. ConclusionsDirectional programming can further increase the reduction in the total daily dose of ApMed after STN-DBS. In addition, directional stimulation can have additional beneficial effects on the global HRQoL. The greater reduction of ApMed doses did not require more energy-consuming stimulation with directional stimulation.

Zonisamide Ameliorates Microglial Mitochondriopathy in Parkinson's Disease Models.

Mitochondrial dysfunction and exacerbated neuroinflammation are critical factors in the pathogenesis of both familial and non-familial forms of Parkinson’s disease (PD). This study aims to understand the possible ameliorative effects of zonisamide on microglial mitochondrial dysfunction in PD. We prepared 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and lipopolysaccharide (LPS) co-treated mouse models of PD to investigate the effects of zonisamide on mitochondrial reactive oxygen species generation in microglial cells. Consequently, we utilised a mouse BV2 cell line that is commonly used for microglial studies to determine whether zonisamide could ameliorate LPS-treated mitochondrial dysfunction in microglia. Flow cytometry assay indicated that zonisamide abolished microglial reactive oxygen species (ROS) generation in PD models. Extracellular flux assays showed that LPS exposure to BV2 cells at 1 μg/mL drastically reduced the mitochondrial oxygen consumption rate (OCR) and extracellular acidification rate (ECAR). Zonisamide overcame the inhibitory effects of LPS on mitochondrial OCR. Our present data provide novel evidence on the ameliorative effect of zonisamide against microglial mitochondrial dysfunction and support its clinical use as an antiparkinsonian drug.

Efficacy of Acupuncture for Parkinson's Disease Anxiety: Two-Stage Protocol for a Randomized Controlled Clinical Trial.

Parkinson's disease anxiety (PDA) is a nonmotor symptom of Parkinson's disease (PD) that is often neglected. PDA poses a far-reaching challenge to the treatment of PD. Acupuncture could be successful in the treatment of PDA. However, the evidence for this is still limited. We propose a two-stage clinical trial. In stage 1, a total of 70 volunteers with PDA will be randomly assigned to either acupuncture (manual acupuncture) or control group (sham acupuncture) in a 1 : 1 ratio. Treatments will be performed for four weeks. The change in the Hamilton Rating Scale for Anxiety (HAMA) score from baseline to week 4 and week 12 will be the primary outcome. The levels of adrenocorticotropic hormone (ACTH), cortisol (CORT), serotonin (5-HT), and corticotropin-releasing factor (CRH) in the patients' serum and the scores on the Hoehn–Yahr Rating Scale and the Unified Parkinson's Disease Rating Scale (UPDRS) will all be considered among the secondary outcomes. Participants will be followed up until week 12. In stage 2, a total of 82 volunteers with PDA will be randomly assigned to either an acupuncture (manual acupuncture) or a control group (anti-Parkinson drugs only) in a 1 : 1 ratio. HAMA score will be the primary outcome. Universality, feasibility and cost effectiveness, Hoehn–Yahr Rating Scale, UPDRS, and serological indicators will be secondary outcomes. Participants will be followed up until week 4. The statistical analysis will include all the allocated individuals. The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine's Research Ethical Committee authorized this procedure, and the trial is registered with ChiCTR2100047253.

Simple and Economical Process for Producing Amantadine Hydrochloride.

A simple and economical process for producing amantadine hydrochloride (1) on a 250 g scale, an antiviral and anti-Parkinson drug, has been developed. Several methods for the preparation of 1 through intermediate N-(1-adamantyl)-acetamide (4) in four or three steps were reported. These procedures started with adamantine (2) or 1-bromoadamantane (3), acetonitrile, and sulfuric acid by using the Ritter-type reaction to obtain N-(1-adamantyl)-acetamide, which was deacetylated to afford 1-amino-adamantane (5) and then the salt formed with anhydrous HCl gives 1 with the overall yield of 1 being 50–58%. In this article, a two-step procedure for the synthesis of 1 from 1-bromadamantane (3) and formamide via N-(1-adamantyl)-formamide (6) in two steps with an overall yield of 88% was reported. In this procedure, the preparation of 6 from 3 is a key step with a yield of 94%, followed by the hydrolysis of 6 with an aq. solution of HCl to give 1 in high yield (93%). The procedure was also carried out under optimal conditions established to reduce the use of toxic reagents or solvents and was carried out in one pot to make it more environmentally friendly. The procedure can be considered as more suitable for the large-scale production of 1. The structures of product 1 and intermediate 6 were confirmed by IR, MS, 1H NMR, 13C NMR.

Using Machine Learning to Identify Patients at High Risk of Inappropriate Drug Dosing in Periods with Renal Dysfunction.

PurposeDosing of renally cleared drugs in patients with kidney failure often deviates from clinical guidelines, so we sought to elicit predictors of receiving inappropriate doses of renal risk drugs.Patients and methodsWe combined data from the Danish National Patient Register and in-hospital data on drug administrations and estimated glomerular filtration rates for admissions between 1 October 2009 and 1 June 2016, from a pool of about 2.6 million persons. We trained artificial neural network and linear logistic ridge regression models to predict the risk of five outcomes (>0, ≥1, ≥2, ≥3 and ≥5 inappropriate doses daily) with index set 24 hours after admission. We used time-series validation for evaluating discrimination, calibration, clinical utility and explanations.ResultsOf 52,451 admissions included, 42,250 (81%) were used for model development. The median age was 77 years; 50% of admissions were of women. ≥5 drugs were used between admission start and index in 23,124 admissions (44%); the most common drug classes were analgesics, systemic antibacterials, diuretics, antithrombotics, and antacids. The neural network models had better discriminative power (all AUROCs between 0.77 and 0.81) and were better calibrated than their linear counterparts. The main prediction drivers were use of anti-inflammatory, antidiabetic and anti-Parkinson's drugs as well as having a diagnosis of chronic kidney failure. Sex and age affected predictions but slightly.ConclusionOur models can flag patients at high risk of receiving at least one inappropriate dose daily in a controlled in-silico setting. A prospective clinical study may confirm that this holds in real-life settings and translates into benefits in hard endpoints.

Structural exploration of selected C6 and C7-substituted coumarin isomers as selective MAO-B inhibitors

Monoamine Oxidase B is considered a successful target for developing antiparkinsonian drugs. Due to the side effects of current MAO-B inhibitors, there’s an urgent need for novel potent and highly selective MAO-B inhibitors. A recent study has shown that coumarins tend to be more selective towards MAO-B than MAO-A when connected to a hex-5-ynyloxy chain at position 6 in contrast to their C7-isomers. The present study describes the mode of interaction of the C6 and C7-substituted coumarin isomers characterized by their difference in selectivity towards MAO-B through molecular docking and molecular dynamics simulations in an effort to elucidate the structural components and molecular interactions that may be responsible for MAO-B selectivity. Three isomeric coumarin pairs connected to ether chain at position 6 or 7 were taken from the literature and modelled according to their IUPAC nomenclature. Molecular docking study revealed one π- π stacking interaction with Tyr-326 in common between the selective coumarin C6-isomers. Resulting complexes of one isomeric coumarin pair that displayed the highest selectivity shift towards MAO-B were subject to 100 ns molecular dynamics simulations study to analyze the stability of the docked complexes. Molecular dynamics revealed that the C7-isomer is relatively stable in both MAO isoforms through the simulation duration, whereas the C6-isomer deemed unstable for MAO-A which may be due to the bulky Phe-208 residue in MAO-A. Our results might be applied for further development and optimization of coumarin derivatives into a successful drug against Parkinson’s disease. Communicated by Ramaswamy H. Sarma

Label-free LC-HRMS-based enzymatic activity assay for the detection of DDC, MAO and COMT inhibitors

Pharmacological treatment of Parkinson’s disease consists of a combined chemotherapy that mostly relies on levodopa (L-DOPA) administration together with inhibitors of dopa-decarboxylase (DDC), monoamine oxidase (MAO) and catechol-methyltransferase (COMT). Identification of inhibitors specifically targeting these enzymes is still a significative part of the development of new alternative antiparkinsonian drugs. Most of the available methods use measurement of enzymatic reactions through radioactive labeling, antibody-recognized products or coupled enzymatic assays. Mass spectrometry (MS) represents an interesting alternative approach as it allows direct and specific detection and quantification of enzymatic reactions. We describe the development of a simple, reliable, label-free assay based on high-resolution mass spectrometry (HRMS) for the detection and relative quantification of three different enzymatic reactions using non-isolated enzymes. The assay was applied both to reference drugs and plant crude extracts. This method can be used to detect hits in extracts libraries as well as determine relative IC50 of inhibitors.

Dopamine D2L receptor density influences the recruitment of β-arrestin2 and Gi1 induced by antiparkinsonian drugs

IntroductionBrain imaging studies have highlighted that the density of dopamine D2 receptors markedly fluctuates across the stages of Parkinson's disease and in response to pharmacological treatment. Moreover, receptor density constitutes a molecular determinant for the signaling profile of D2 receptor ligands. We therefore hypothesized that variations in receptor expression could influence D2 receptor response to antiparkinsonian drugs, most notably with respect to the recruitment bias between Gi1 and β-arrestin2. MethodsThe recruitment bias of dopamine, pramipexole, ropinirole, and rotigotine was examined using a nanoluciferase-based biosensor for probing the interactions of the D2L receptor with either Gi1 or β-arrestin2. The characterization of the functional selectivity of these D2 receptor agonists was performed at two distinct D2L receptor densities by taking advantage of a cell model carrying an inducible system that enables the overexpression of the D2L receptor when exposed to doxycycline. ResultsA high receptor density oriented the balanced signaling profile of dopamine towards a preferential recruitment of Gi1. It also moderated the marked Gi1 and β-arrestin2 biases of pramipexole and rotigotine, respectively. At variance, the Gi1 bias of ropinirole appeared as not being influenced by D2L receptor density. ConclusionsTaken together, these observations highlight receptor density as a key driver of the signaling transducer recruitment triggered by antiparkinsonian agents. Moreover, given the putative beneficial properties of β-arrestin2 in promoting locomotion, this study provides molecular insights that position the arrestin-biased ligand rotigotine as a putatively more beneficial D2 receptor agonist for the treatment of early and late Parkinson's disease.

Anti-Parkinson Drug from Chemical Medicines and Herbal Medicines: A Review

Parkinson's disease (PD) is a disease of the central nervous system. It is a progressive disorder, meaning it gets worse over time. PD usually characterized by tremor, rigidity, akinesia and postural autonomic instability. In addition, it may also cause a series of non-motor symptoms (NMSs). This disease affects a small area of cells in the middle of the brain. This area is called the substantia nigra (SNc). The cells slowly lose their ability to produce a chemical called dopamine. The disease usually appears in the age over 60 years. Nowadays, a lot of anti-Parkinson drugs have been found either from that of chemicals or herbs. In this essay anti-Parkinson drugs from chemical medicine and herbal medicines especially from china will be discussed. Anti-Parkinson's drugs are derived from chemical medicines include levodopa (l-dopa), dopamine agonists, MAO-B inhibitors, catechol O-methyltransferase (COMT) inhibitors, anticholinergics and amantadine. Meanwhile, anti-Parkinson drugs derived from herbal medicine include Scutellaria baicalensis Georgi, Polygonum cuspidatum Sieb. et Zucc., green tea (Camellia sinensis L.), Panax ginseng C. A. Mey., Cistanche deserticola Y. C. Ma, Panax Notoginseng Wall. var notoginseng (Burkill.) F.H. Chen, Gastrodia elata Blume and Polygala tenuifoliaWilld.. These drugs have the same effects to help ease symptoms of Parkinson’s and can increase the amount of dopamine in substantia nigra pars compacta (SNc). However, some chemical drugs have more side effects although herbal medicines are less clear, more tests need to be planned.

Adesão terapêutica ao uso de antiparkinsonianos em pessoas idosas e seus fatores associados: revisão integrativa

Abstract Objectives To identify factors associated with antiparkinson drugs use and adherence in older adults with Parkinson's disease (PD) through an integrative literature review. Method An integrative literature review involving a search for relevant publications in Portuguese, English, and Spanish on the electronic databases LILACS, MEDLINE - via PubMed, Web of Science and Scopus, without restriction regarding date or study design, was carried out during the period August-September 2021. The selection of studies was performed independently by two reviewers and the final validation conducted by a third reviewer. Results After applying the eligibility criteria, 5 of the 460 studies found were included in the review. Results showed moderate adherence rates (range 35.3-66.8%) and the main factors associated with lower adherence to antiparkinson therapy were older age, cognitive deficit, greater motor impairment, multimorbidities, change in therapy regimens, depression, polypharmacy, lower education, non-white ethnicity and male gender. Factors associated with greater adherence were younger age, white ethnicity, no change in therapy regimen, higher level of knowledge about PD, good clinical control, higher educational level, married status, higher income and greater level of awareness. Conclusions Non-adherence to antiparkinsonian therapy was frequent and multifactorial., Understanding this behavior is important to help inform the scientific community and devise public policies and strategic planning in health services for improving the quality of life of the older population.

Antiparkinson drugs use and adherence in older adults and associated factors: an integrative review

Resumo Objetivos Identificar os fatores associados à adesão terapêutica ao uso de antiparkinsonianos em idosos com Doença de Parkinson (DP) por meio de uma revisão integrativa da literatura. Método Trata-se de uma revisão integrativa de literatura nos idiomas português, inglês, espanhol, nas bases de dados eletrônicas LILACS, MEDLINE - via PubMed, Web of Science e Scopus, sem restrição quanto ao tempo e desenho de estudo, realizada no período de agosto a setembro de 2021. A seleção dos estudos foi realizada de maneira independente por dois revisores e a validação final por um terceiro revisor. Resultados Após a aplicação dos critérios de elegibilidade, dos 460 estudos encontrados, foram incluídos cinco estudos que evidenciam taxas moderadas de adesão, variando de 35,3% a 66,8%, e apontam como principais fatores associados à menor adesão à terapia antiparkinsoniana: idade mais avançada, deficit cognitivo, maior comprometimento motor, multimorbidades, alteração nos regimes terapêuticos, depressão, polifarmácia, menor escolaridade, não brancos e sexo masculino. Foram fatores descritos para maior adesão: idade mais jovem, cor branca, sem modificação de regime terapêutico, maior nível de conhecimento sobre a DP, bom controle clínico, educação, ser casado, maior renda e nível de consciência. Conclusões A não adesão à terapêutica antiparkinsoniana é frequente e de dimensão multifatorial, sua compreensão torna-se relevante para subsidiar dados para a comunidade científica, objetivando a criação de políticas públicas e planejamento estratégico em serviços de saúde com o propósito de melhorar a qualidade de vida da pessoa idosa.

Влияние современной лекарственной терапии на течение болезни Паркинсона

The impact of the therapy on patients with Parkinson’s disease remains unclear. To date, claims about the pathogenesis-modifying effect of drugs remain controversial. One of the criteria for the effect of therapy on changing the course of Parkinson’s disease should be an increased life expectancy, a reduction in severe forms and, accordingly, disability. It is only possible to assess the impact of modern therapy by comparing it with a group of patients with Parkinson’s disease who never received modern antiparkinsonian drugs. The purpose — to study the impact of modern pharmacotherapy on the course of PD based on the data of medical care quality during five years. Material and methods. A five-year analysis of the conclusions of medical examinations of 1754 patients with Parkinson’s disease, as well as a comparative statistical analysis of the causes of death in the study group compared with the general Russian population in 2018 and a sample of M. Hoehn and M. Yahr 1967, before the use of modern antiparkinsonian drugs. Results. Out of 1754 people, 1480 patients remained in the study after 5 years. Despite the ongoing drug therapy in accordance with clinical recommendations and standards adopted in the Russian Federation, during the observed period, there was a steady progression of Parkinson’s disease and transition to more severe stages. The mortality rate in the study group from circulatory diseases was significantly higher (p < 0.001) compared to the general Russian population and significantly higher (p < 0.01) compared to the group of M. Hoehn and M. Yahr in 1967, which does not exclude the negative impact of antiparkinsonian drugs. It was interesting to find a reliable fact that in the group of our study, the probability of death from respiratory diseases was 2.23 times higher (p < 0.01) than in the group of Russian citizens in 2018, but 2.38 times lower (p < 0.02) than in the group of M. Hoehn and M. Yahr in 1967, which can be explained by the mutually contradictory effect of antiparkinsonian therapy. Conclusions. Тhe study established the fact of clinical progression of the disease, despite the ongoing therapy. Over a five-year period, the number of patients in the group with a more severe course of the disease (stages III–IV for Hoehn and Yahr) increased significantly (p < 0.001). The main causes of death of patients with Parkinson’s disease in our study coincide with the causes of death of Russian citizens in the general population in 2018, as well as with the sample presented by M. Hoehn and M. Yahr in 1967 in the era before the use of modern antiparkinsonian drugs. Modern antiparkinsonian drugs can have both a positive and negative effect on a patient with Parkinson’s disease, having an ambiguous effect on life expectancy.

A novel neuroprotective cholinesterase-monoamine oxidase inhibitor for treatment of dementia and depression in Parkinson’s disease

The current novel therapeutic approach suggests that multi-targeted compounds, with diverse biological activities but a single set of bioavailability and pharmacokinetics, will be significantly more advantageous in the treatment of the complex pathology of Parkinson’s diseases (PD) than traditional therapies. This review introduces a novel cholinesterase (ChE)-monoamine oxidase (MAO) inhibitor, namely MT-031, which was designed by amalgamating the propargyl moiety of the irreversible selective MAO-B inhibitor and neuroprotective/neurorestorative anti-Parkinsonian drug, rasagiline, into the methylamino position of the ChE inhibitor anti-AD drug, rivastigmine. MT-031 possesses neuroprotective, cognition enhancing, anti-depressant, and anti-inflammatory properties both in vitro and in vivo. Altogether, these findings suggest that MT-031 may be a potential treatment for combating PD and associated dementia and depression.

Pharmacotherapeutics and molecular docking studies of alpha-synuclein modulators as promising therapeutics for Parkinson’s disease

Parkinson’s disease (PD) is an age-related neurodegenerative ailment that affects dopamine-producing neurons in a specific area of the brain called the substantia nigra of the ventral midbrain. It is clinically characterized by movement disorder and marked with unusual synaptic protein alpha-synuclein accumulation in the brain. To date, only a few Food and Drug Administration (FDA) approved drugs are available on the market for the treatment of PD. Nonetheless, these drugs show parasympathomimetic related adverse events and remarkably higher toxicity; hence, it is important to find more efficacious molecules to treat PD. In our study, We chosen 22 natural compounds as inhibitors that potentially block the alpha-synuclein clump—the pathological hallmark of PD—and provide new avenues for its treatment. Most of these molecules exhibited good pharmacokinetic behaviors, making them decisively favorable drug candidates to cure PD. Molecular docking studies were performed to investigate the binding interactions between natural compounds and alpha-synuclein as anti-Parkinson drug targets. Among the examined compounds, curcumin and piperine emerged as promising phytochemicals with the highest binding affinity, key residual stable bindings and showed a good inhibitory features. Thus, the present study indicates that curcumin and piperine hold the potential to be developed as treatment options against PD. Experimental validations are needed for insights into their mechanism of action and potential clinical application.

General Anesthesia Management during Surgical Fixation of a Zygomatic and Maxillary Fracture in a Patient Taking Multiple Anti-Parkinsonian Drugs

General Anesthesia Management during Surgical Fixation of a Zygomatic and Maxillary Fracture in a Patient Taking Multiple Anti-Parkinsonian Drugs

Comparison of pramipexole versus ropinirole in the treatment of Parkinson's disease.

Parkinson's disease is a progressive neurodegenerative disease characterized by motor and non-motor symptoms. Levodopa is the most effective drug in the symptomatic treatment of the disease. Dopamine receptor agonists provide sustained dopamin-ergic stimulation and have been found to delay the initiation of levodopa treatment and reduce the frequency of various motor complications due to the long-term use of levodopa. The primary aim of this study was to compare the efficacy of potent nonergoline dopamine agonists pramipexole and ropinirole in both "dopamine agonist monotherapy group" and "levodopa add-on therapy group" in Parkinson's disease. The secondary aims were to evaluate the effects of these agents on depression and the safety of pramipexole and ropinirole. A total of 44 patients aged between 36 and 80 years who were presented to the neurology clinic at Ministry of Health Diskapi Yildirim Beyazit Training and Research Hospital, Ankara, Turkey and were diagnosed with idiopathic Parkinson's disease, were included into this randomized parallel-group clinical study. Dopamine agonist monotherapy and levodopa add-on therapy patients were randomized into two groups to receive either pramipexole or ropinirole. The maximum daily dosages of pramipexole and ropinirole were 4.5 mg and 24 mg respectively. Patients were followed for 6 months and changes on Unified Parkinson's Disease Rating Scale, Clinical Global Impression-severity of illness, Clinical Global Impression-improvement, Beck Depression Inven-tory scores, and additionally in advanced stages, changes in levodopa dosages were evaluated. Drug associated side effects were noted and compared. In dopamine agonist monotherapy group all of the subsections and total scores of Unified Parkinson's Disease Rating Scale and Clinical Global Impression-severity of illness of the pramipexole subgroup showed significant improvement particularly at the end of the sixth month. In the pramipexole subgroup of levodopa add-on therapy group, there were significant improvements on Clinical Global Impression-severity of illness and Beck Depression Inventory scores, but we found significant improvement on Clinical Global Impression-severity of illness score at the end of the sixth month in ropinirole subgroup too. The efficacy of pramipexole and ropinirole as antiparkinsonian drugs for monotherapy and levodopa add-on therapy in Parkinson's disease and their effects on motor complications when used with levodopa treatment for add-on therapy have been demonstrated in several previous studies. This study supports the effectiveness and safety of pramipexole and ropinirole in the monotherapy and levodopa add-on therapy in the treatment of Parkinson's disease.

Orthostatic Hypotension and Antiparkinsonian Drugs: A Systematic Review and Meta-analysis.

BackgroundOrthostatic hypotension (OH) is multifactorial in Parkinson’s disease (PD). Antiparkinsonian medication can contribute to OH, leading to increased risk of falls, weakness and fatigue.MethodsWe conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) of antiparkinsonian drugs associated with OH as an adverse effect, compared to placebo. We searched EMBASE, MEDLINE and Web of Science databases until November 2020. Analysis used fixed-effects models and the GRADE tool to rate quality of evidence. Meta-analysis was performed if 3 or more studies of a drug group were available.ResultsTwenty-one RCTs including 3783 patients were included comparing 6 PD drug groups to placebo (MAO-B inhibitors, dopamine agonists, levodopa, COMT inhibitors, levodopa and adenosine receptor antagonists). OH was recorded as an adverse event or measurement of vital signs, without further specification on how this was defined or operationalised. Meta-analysis was performed for MAO-B inhibitors and dopamine agonists, as there were 3 or more studies for these drug groups. In this analysis, compared with placebo, neither MAO-B inhibitors or dopamine agonists were associated with increased risk of OH, (OR 2.28 [95% CI:0.81–6.46]), (OR 1.39 [95% CI:0.97–1.98]).ConclusionsMost studies did not specifically report OH, or reporting of OH was limited, including how and when it was measured. Furthermore, studies specifically reporting OH included participants that were younger than typical PD populations without multimorbidity. Future trials should address this, for example,, by including individuals over the age of 75, to improve estimations of how antiparkinsonian medications affect risk of OH.