Antiparkinsonian Drugs Research Articles

AI molecular property prediction for Parkinson's Disease reveals potential repurposing drug candidates based on the increase of the expression of PINK1

Background and ObjectiveParkinson's Disease (PD), a common neurodegenerative disorder and one of the major current challenges in neuroscience and pharmacology, may potentially be tackled by the modern AI techniques employed in drug discovery based on molecular property prediction. The aim of our study was to explore the application of a machine learning setup for the identification of the best potential drug candidates among FDA approved drugs, based on their predicted PINK1 expression-enhancing activity. MethodsOur study relies on supervised machine learning paradigm exploiting in vitro data and utilizing the scaffold splits methodology in order to assess model's capability to extract molecular patterns and generalize from them to new, unseen molecular representations. Models' predictions are combined in a meta-ensemble setup for finding new pharmacotherapies based on the predicted expression of PINK1. ResultsThe proposed machine learning setup can be used for discovering new drugs for PD based on the predicted increase of expression of PINK1. Our study identified nitazoxanide as well as representatives of imidazolidines, trifluoromethylbenzenes, anilides, nitriles, stilbenes and steroid esters as the best potential drug candidates for PD with PINK1 expression-enhancing activity on or inside the cell's mitochondria. ConclusionsThe applied methodology allows to reveal new potential drug candidates against PD. Next to novel indications, it allows also to confirm the utility of already known antiparkinson drugs, in the new context of PINK1 expression, and indicates the potential for simultaneous utilization of different mechanisms of action.

Treatment Detection and Movement Disorder Society-Unified Parkinson's Disease Rating Scale, Part III Estimation Using Finger Tapping Tasks.

The validation of objective and easy-to-implement biomarkers that can monitor the effects of fast-acting drugs among Parkinson's disease (PD) patients would benefit antiparkinsonian drug development. We developed composite biomarkers to detect levodopa/carbidopa effects and to estimate PD symptom severity. For this development, we trained machine learning algorithms to select the optimal combination of finger tapping task features to predict treatment effects and disease severity. Data were collected during a placebo-controlled, crossover study with 20 PD patients. The alternate index and middle finger tapping (IMFT), alternative index finger tapping (IFT), and thumb-index finger tapping (TIFT) tasks and the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III were performed during treatment. We trained classification algorithms to select features consisting of the MDS-UPDRS III item scores; the individual IMFT, IFT, and TIFT; and all three tapping tasks collectively to classify treatment effects. Furthermore, we trained regression algorithms to estimate the MDS-UPDRS III total score using the tapping task features individually and collectively. The IFT composite biomarker had the best classification performance (83.50% accuracy, 93.95% precision) and outperformed the MDS-UPDRS III composite biomarker (75.75% accuracy, 73.93% precision). It also achieved the best performance when the MDS-UPDRS III total score was estimated (mean absolute error: 7.87, Pearson's correlation: 0.69). We demonstrated that the IFT composite biomarker outperformed the combined tapping tasks and the MDS-UPDRS III composite biomarkers in detecting treatment effects. This provides evidence for adopting the IFT composite biomarker for detecting antiparkinsonian treatment effect in clinical trials. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Trends in hospital admission related to poisoning by, narcotics and psychodysleptics and poisoning by antiepileptic, sedative-hypnotic, and antiparkinsonism drugs in England and Wales between April 1999 and April 2020: An ecological study

BackgroundThis study aimed to investigate the trend of hospital admissions related to poisoning by narcotics and psychodysleptics and poisoning by antiepileptic, sedative-hypnotic, and antiparkinsonism drugs in England and Wales between April 1999 and April 2020. MethodsAn observational ecological study were conducted using data from the Hospital Episode Statistics database in England and the Patient Episode Database for Wales. The rate of hospital admissions with 95% confidence intervals (CIs) was calculated by dividing the number of episodes of poisoning by narcotics and psychodysleptics related admission and poisoning by antiepileptic, sedative-hypnotic, and antiparkinsonism drugs-related admission by the mid-year population from the Office for National Statistics. All analyses were conducted using SPSS version 27. ResultsThe total annual number of hospital admissions for narcotics and psychodysfunctionals poisonings increased by 1.40-fold [from 15.70 (95% CI 15.36–16.04) in 1999 to 37.64 (95% CI 37.15–38.13) in 2020 per 100,000 people, p < 0.01]. However, the overall annual number of poisonings by antiepileptic, sedative-hypnotic and antiparkinsonism drugs hospital admissions for various reasons decreased by 12.8% [from 33.55 (95% CI 33.05–34.04) in 1999 to 29.26 (95% CI 28.82–29.69) in 2020 per 100,000 persons, p < 0.05]. Poisoning by other opioids (53.2%), heroin (15.1%), and other synthetic narcotics (13.3%) were the most common reasons for narcotic and psychodysfunctional poisoning. While poisoning by benzodiazepines (54.2%) and poisoning: other antiepileptic and sedative-hypnotic drugs (30.7%) were the most common hospital admission reasons for poisoning by antiepileptic, sedative-hypnotic, and antiparkinsonism. ConclusionPoisoning by narcotics have increased in England and Wales over the study period, however, poisoning by antiepileptic, sedative-hypnotic, and antiparkinsonism drugs in England and Wales were relatively stable during the same period. Future initiatives and awareness programs to prevent harmful use and drug poisoning by narcotics, sedative-hypnotic and other medications are needed.

Systematic assessment of non-medical use of prescription drugs using doctor-shopping indicators: A nation-wide, repeated cross-sectional study.

The aim of this study was to present the first nation-wide, systematic, repeated assessment of doctor-shopping (i.e. visiting multiple physicians to be prescribed the same drug) during 10years for more than 200 psychoactive prescription drugs in the 67 million inhabitants in France. This was a nation-wide, repeated cross-sectional study. Data are from the French National Health Data System in 2010, 2015 and 2019 for 214 psychoactive prescription drugs (i.e. anaesthetics, analgesics, antiepileptics, anti-Parkinson drugs, psycholeptics, psychoanaleptics, other nervous system drugs and antihistamines for systemic use). The detection and quantification of doctor-shopping relied upon an algorithm that detects overlapping prescriptions from repeated visits to different physicians. We used two doctor-shopping indicators aggregated at population level for each drug dispensed to more than 5000 patients: (i) the quantity doctor-shopped, expressed in defined daily doses (DDD), which measures the total quantity doctor-shopped by the study population for a given drug; and (ii) the proportion doctor-shopped, expressed as a percentage, which standardizes the quantity doctor-shopped according to the use level of the drug. The analyses included approximately 200 million dispensings to approximately 30 million patients each year. Opioids (e.g. buprenorphine, methadone, morphine, oxycodone and fentanyl), benzodiazepines and non-benzodiazepine hypnotics (Z-drugs) (e.g. diazepam, oxazepam, zolpidem and clonazepam) had the highest proportions doctor-shopped during the study period. In most cases, the proportion and the quantity doctor-shopped increased for opioids and decreased for benzodiazepines and Z-drugs. Pregabalin had the sharpest increase in the proportion doctor-shopped (from 0.28 to 1.40%), in parallel with a sharp increase in the quantity doctor-shopped (+843%, from 0.7 to 6.6DDD/100 000 inhabitants/day). Oxycodone had the sharpest increase in the quantity doctor-shopped (+1000%, from 0.1 to 1.1DDD/100 000 inhabitants/day), in parallel with a sharp increase in the proportion doctor-shopped (from 0.71 to 1.41%). Detailed results for all drugs during the study period can be explored interactively at: https://soeiro.gitlab.io/megadose/. In France, doctor-shopping occurs for many drugs from many pharmacological classes, and mainly involves opioid maintenance drugs, some opioids analgesics, some benzodiazepines and Z-drugs and pregabalin.

Transdermal Microneedle-Mediated Delivery of Rasagiline Nanoparticles.

In the transdermal drug delivery system, the drug is administered through the skin and attains a systemic effect. It is a drug administration route that includes drug transport to the epidermis and potentially dermal tissue of the skin for locally therapeutic effect, while an exceptionally significant drug division is transported in systemic blood circulation. This study aimed to formulate rasagiline mesylate (RM) as a transdermal microneedle (MN) delivery. The RM is an antiparkinson drug that can be classified as class III with low permeability and subjected to extensive first-pass metabolism. At first, it was formulated as nanoparticles using the chitosan polymer and ion gelation method. Afterward, the prepared nanoparticles were incorporated into a transdermal MN formulated by a polydimethylsiloxane template. The two-step casting process uses two polymer concentrations of polyvinyl alcohol and mixes them with other polymers in a 3:1 ratio (polyvinylpyrrolidone and chitosan) and glycerin as a plasticizer. The selected MN formula was MN4 with a promising shape, no bubbles, fine and well-formed sharp needles that passed the folding endurance test with 130 folding times before broken, drug content of 97±10.02%, and ex vivo permeation. The results showed a significant (P>0.05) permeability enhancement and increase of flux (160%), compared to the transdermal patch. The RS polymeric nanoparticles were successfully prepared and loaded within dissolving MNs of sufficient mechanical strength to penetrate the stratum corneum and enhance the amount permeated through it to induce the systemic effect transdermally.

Antiparkinsonian Medication Reconciliation as a Strategy to Improve Safety by Preventing Medication Errors.

About 70% of neurologists report that PD patients do not get their medication properly when hospitalized, and 33% are prescribed contraindicated drugs. To execute medication reconciliation (MedRec) focused on antiparkinsonian drugs to identify, characterize and, eventually, prevent medication errors, thus promoting therapeutic quality and safety in daily practice. An interventional, single-center, 1 year, prospective study. All the patients who were hospitalized and had, at least, one active prescription containing an antiparkinsonian drug at hospital admission were included. MedRec was performed by following a three-phased check: inpatient electronic prescription validation after assessing the outpatient medication schedule, review of the latest clinical report emitted by the Neurology Department/General Practitioner, and pharmacist-driven interview of the patient and/or caregiver to confirm the information regarding medication gathered. A total of 171 admission episodes from 132 patients were registered (February 1, 2021, and January 31, 2022). Of 224 prescription lines involving antiparkinsonian drugs, 179 contained, at least, one medication error (59.8%). Commission errors (91.62%) were more frequent than omitted drugs (8.38%). The most common medication errors were related to timing (41.90%), frequency (21.23%), and dosing (19.55%). The implementation of this program prevented the erroneous administration of 2716 antiparkinsonian doses, 60% of the total number of doses prescribed. Interestingly, a significant relationship between the number of medication errors and having levodopa prescribed was evidenced (P < 0.05). A contraindicated drug was prescribed in almost one-third of the episodes (29.82%). Clinical pharmacists' implementation of an antiparkinsonians reconciliation program sharply reduced medication errors and prescription of contraindicated drugs.

Levodopa Dose Equivalency in Parkinson's Disease: Updated Systematic Review and Proposals.

To compare drug regimens across clinical trials in Parkinson's disease (PD) conversion formulae between antiparkinsonian drugs have been developed. These are reported in relation to levodopa as the benchmark drug in PD pharmacotherapy as 'levodopa equivalent dose' (LED). Currently, the LED conversion formulae proposed in 2010 by Tomlinson et al. based on a systematic review are predominantly used. However, new drugs with established and novel mechanisms of action and novel formulations of longstanding drugs have been developed since 2010. Therefore, consensus proposals for updated LED conversion formulae are needed. To update LED conversion formulae based on a systematic review. The MEDLINE, CENTRAL, and Embase databases were searched from January 2010 to July 2021. Additionally, in a standardized process according to the GRADE grid method, consensus proposals were issued for drugs with scarce data on levodopa dose equivalency. The systematic database search yielded 3076 articles of which 682 were eligible for inclusion in the systematic review. Based on these data and the standardized consensus process, we present proposals for LED conversion formulae for a wide range of drugs that are currently available for the pharmacotherapy of PD or are expected to be introduced soon. The LED conversion formulae issued in this Position Paper will serve as a research tool to compare the equivalence of antiparkinsonian medication across PD study cohorts and facilitate research on the clinical efficacy of pharmacological and surgical treatments as well as other non-pharmacological interventions in PD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

High-resolution structural information of membrane-bound α-synuclein provides insight into the MoA of the anti-Parkinson drug UCB0599

α-synuclein (αS) is an intrinsically disordered protein whose functional ambivalence and protein structural plasticity are iconic. Coordinated protein recruitment ensures proper vesicle dynamics at the synaptic cleft, while deregulated oligomerization on cellular membranes contributes to cell damage and Parkinson's disease (PD). Despite the protein's pathophysiological relevance, structural knowledge is limited. Here, we employ NMR spectroscopy and chemical cross-link mass spectrometry on 14N/15N-labeled αS mixtures to provide for the first time high-resolution structural information of the membrane-bound oligomeric state of αS and demonstrate that in this state, αS samples a surprisingly small conformational space. Interestingly, the study locates familial Parkinson's disease mutants at the interface between individual αS monomers and reveals different oligomerization processes depending on whether oligomerization occurs on the same membrane surface (cis) or between αS initially attached to different membrane particles (trans). The explanatory power of the obtained high-resolution structural model is used to help determine the mode-of-actionof UCB0599. Here, it is shown that the ligand changes the ensemble of membrane-bound structures, which helps to explain the success this compound, currently being tested in Parkinson's disease patients in a phase 2 trial, has had in animal models of PD.

Cannabidiol improves haloperidol-induced motor dysfunction in zebrafish: a comparative study with a dopamine activating drug

BackgroundCannabidiol (CBD) extracted from the cannabis plant is believed to have a medicinal value due to its neuroprotective effect via anti-inflammatory and antioxidant action. Recent behavioral studies in rats have reported that CBD mediates serotonin (5-HT1A) receptor action to improve motor dysfunction induced by dopamine (D2) receptor blockade. In particular, its effect on D2 receptor blockade in the striatum is an important function associated with neurological disorders resulting from various extrapyramidal motor dysfunctions. Dopaminergic neurodegeneration associated with this site is known for inducing Parkinson’s disease (PD), which often affects the elderly. It is also known to cause drug-induced Parkinsonism. This study examines the ameliorating effect of CBD, which does not act directly on D2 receptors, against drug-induced motor dysfunction induced by the antipsychotic drug (haloperidol).MethodsWe created a drug-induced Parkinsonism model in zebrafish larvae using an antipsychotic drug (haloperidol). We evaluated the distance traveled and repetitive light-stimulation response. Furthermore, we examined whether administration of several concentrations of CBD ameliorates symptoms of the Parkinsonism model and compared its effects with those of antiparkinsonian drug ropinirole.ResultsCBD concentrations equal to half of haloperidol’s resulted in an almost complete reversal of haloperidol-induced motor dysfunction, as measured by the distance traveled by the zebrafish and their response to light-stimulus. While ropinirole also significantly reversed haloperidol’s effects at the same concentration as CBD, CBD was more effective than ropinirole.ConclusionsCBD-induced motor dysfunction improvement via D2 receptor blockade is a potential novel mechanism for the treatment of haloperidol-induced motor dysfunction.

The combination of levodopa with levodopa-metabolizing enzyme inhibitors prevents severe fever with thrombocytopenia syndrome virus infection in vitro more effectively than single levodopa

Severe fever with thrombocytopenia syndrome is a hemorrhagic fever caused by a tick-borne infection. The causative agent, Dabie bandavirus, is also called the severe fever with thrombocytopenia syndrome virus (SFTSV). Ogawa et al. (2022) reported that levodopa, an antiparkinsonian drug with an o-dihydroxybenzene backbone, which is important for anti-SFTSV activity, inhibited SFTSV infection. Levodopa is metabolized by dopa decarboxylase (DDC) and catechol-O-methyltransferase (COMT) in vivo. We evaluated the anti-SFTSV efficacy of two DDC inhibitors, benserazide hydrochloride and carbidopa, and two COMT inhibitors, entacapone and nitecapone, which also have an o-dihydroxybenzene backbone. Only DDC inhibitors inhibited SFTSV infection with pretreatment of the virus (half-maximal inhibitory concentration [IC50]: 9.0–23.6 μM), whereas all the drugs inhibited SFTSV infection when infected cells were treated (IC50: 21.3–94.2 μM). Levodopa combined with carbidopa and/or entacapone inhibited SFTSV infection in both conditions: pretreatment of the virus (IC50: 2.9–5.8 μM) and treatment of infected cells (IC50: 10.7–15.4 μM). The IC50 of levodopa in the above-mentioned study for pretreatment of the virus and treatment of infected cells were 4.5 and 21.4 μM, respectively. This suggests that a synergistic effect was observed, especially for treatment of infected cells, although the effect is unclear for pretreatment of the virus. This study demonstrates the anti-SFTSV efficacy of levodopa-metabolizing enzyme inhibitors in vitro. These drugs may increase the time for which the levodopa concentration is maintained in vivo. The combination of levodopa and levodopa-metabolizing enzyme inhibitors might be a candidate for drug repurposing.

Psychosis in Parkinson’s Disease: a Case Report of Diagnosis and Management

IntroductionPsychosis is a frequent complication in patients diagnosed with Parkinson’s Disease (PD). Characterized mainly by visual hallucinations and paranoid delusions, it occurs most frequently, but not exclusively, as an adverse effect of antiparkinson medications. Nevertheless, cognitive impairment and dementia, as a frequent feature of PD, needs to be considered for differential diagnosis.ObjectivesOur main objective is to report a case of PD Psychosis, its diagnosis and management and complement it with a non-systematic review of literature.MethodsPatient file consultation and an additional research, based on the key words “Psychosis” and “Parkinson’s Disease”, using Pubmed as database.ResultsA 53-year-old female, diagnosed with Juvenile Parkinson’s Disease since age 45 and, as expected, polimedicated with antiparkinson medication. Without any relevant psychiatric background, she was admitted to the emergency department for disorganized behaviour, with 2 weeks of evolution. There, it was also possible to determine the presence of auditive hallucinations and persecutory delusions, associated with marked anguish.After exclusion of any underlying cause for this symptomatology, inpatient treatment was proposed and accepted by the patient. In collaboration with the Neurology Department, a gradual reduction and optimization of antiparkinson drugs was conducted, associated with introduction of low doses of antipsychotic drugs, in this case Olanzapine. With this medication adjustments, clinical improvement was accomplished, with eventual fading and cessation of psychotic symptoms. Additionally, an irregularly intake of antiparkinson drugs was considered the most probably cause of this clinical decompensation.ConclusionsAs present in literature, due to the chronicity and complexity of PD, stopping all antiparkinson drugs is not an option, even when psychotic symptoms, that could be a consequence of these drugs, are present. Therefore, a rigorous evaluation and management are mandatory, including the exclusion of other underlying causes and a careful therapeutic adjustment, with gradual reduction of antiparkinson drugs, addressing an eventual temporal relationship between the beginning of a specific drug and the onset of symptoms, and verification of therapeutic compliance, including an involuntary overdose. In cases of refractory symptoms, and after a risk-benefit assessment, pharmacologic treatment directed at these symptoms, low doses of anti-psychotics, may be necessary.Disclosure of InterestNone Declared

Psychosis in Parkinson’s disease: a clinical biomarker of disease stage and prognosis

IntroductionParkinson’s disease (PD) is a neurodegenerative disorder characterized by motor and nonmotor symptoms, the latter contributing significantly to morbidity, mortality, nursing home placement and quality of life.ObjectivesWe present a literature review about the impact of psychosis on PD’s prognosis.MethodsA literature review is performed on PUBMED, using the next keywords: "Parkinson’s disease”, “psychosis” and “prognosis”. We focused on data from systematic reviews, clinical trials and meta-analysis published in English on last 10 years.ResultsPsychosis is a common feature of Parkinson’s disease, occurring in up to 30% of PD patients treated chronically with antiparkinsonian drugs. Visual hallucinations are the most common psychotic symptom observed, delusions being considerably less common and affecting only 5% of treated patients.Positive symptoms in PD vary across its course: early in the disease, passage hallucinations, illusions and presence hallucinations occur; later, complete visual hallucinations, initially with good insight, then without insight.Psychosis spectrum symptoms in early PD predict a decline in cognitive function at 2 years, especially visual hallucinations. There is an association between visual hallucinations and the subsequent emergence of dementia.ConclusionsCurrent evidence highlights the role of PD psychosis as a clinical biomarker of disease stage, distribution and future progression. Early recognition and treatment of psychotic symptoms improves disease’s outcomes.Disclosure of InterestNone Declared

Antiparkinsonian Potential of Natural Products: Molecular Docking, Prediction of Pharmacokinetic and Toxicological Properties

Background: Parkinson's disease (PD) is a neurodegenerative pathology common in the elderly, and it may be related to several factors, such as excessive and continuous use of drugs, alcoholism, cerebral ischemia, among others. Emphasizing that there is still no cure for PD, current pharmacological treatment aims to restore reduced dopaminergic activity in the central nervous system and manage symptoms. However, due to the different side effects caused by antiparkinsonian drugs, their use is recommended just when symptoms are considerably impairing professional performance or the patient's daily tasks. Therefore, studies for the development of new drugs have been conducted, and natural products are gaining importance due to the possibility of discovering new bioactive molecular. In this sense, this research aimed to perform the in silico study of molecules of natural origin for the treatment of PD. Methods: A search for molecules from medicinal plants was carried out, they underwent a pharmacokinetic and toxicological prediction with subsequent molecular docking study, being coupled with the MAO-B enzyme and the dopamine receptor 2. Results: The ginsenosides compounds present an unfavorable pharmacokinetic pattern, which can be explained by their molecular mass, while the other molecules present average patterns, with the exception of kavains, which obtained very satisfactory results. When it comes to toxicity, the molecules curcumin, dihydrokavain, vitexin, kavain and tetrahydrocurcumin did not exhibit any toxic alert. As for the molecular docking study, the compound curcumin stood out with a considerable number of interactions at many amino acid residues relevant to antiparkinsonian activity, both in the MAO-B enzyme and in the D2 receptor. Conclusion: Of 25 molecules of natural products, 3 are good candidates for studies of oral drugs, owing to their excellent pharmacokinetic profile and low probability of being toxic. The curcumin molecule has a great notoriety, as it obtained relevant interactions with the two proteins studied in molecular docking, speciallyin the MAO-B enzyme.

Delirious episode secondary to rotigotine: the psychotic patch

IntroductionThere is a fine line separating psychiatry and neurology. Most movement disorders can have psychiatric symptoms, not only those caused by the disease itself, but also those induced by the drugs used to treat them.ObjectivesPresentation of a clinical case about a patient diagnosed with Parkinson’s disease presenting a several-month-long delirious episode due to dopaminergic drugs.MethodsLiterature review on drug-induced psychosis episodes in Parkinson’s disease.ResultsA 57-year-old patient with diagnosis of Parkinson’s disease for six years, who went to the emergency room accompanied by his wife due to delirious ideation. He was being treated with levodopa, carbidopa and rasagiline for years, and rotigotine patches whose dosage was being increased over the last few months.His wife reported celotypical clinical manifestations and multiple interpretations of different circumstances occurring around her. He chased her on the street, had downloaded an app to look for a second cell phone because he believed she was cheating on him, and was obsessed with sex. He had no psychiatric background. It was decided to prescribe quetiapine.The following day, he returned because he refused to take the medication since he thought he was going to be put to sleep or poisoned. It was decided to admit him to Psychiatry.During the stay, rasagiline and rotigotine were suspended. Olanzapine and clozapine were introduced, with behavioral improvement and distancing from the psychotic symptoms which motivated the admission. The patient was also motorically stable. Although levodopa is best known for causing psychotic episodes, the symptons were attributed to rotigotine patches for temporally overlapping the dose increase.ConclusionsPsychiatric symptoms are the third most frequent group of complications in Parkinson’s disease after gastrointestinal complications and abnormal movements. All medication used to control motor disorders can lead to psychosis, not only dopaminergics, but also selegiline, amantadine and anticholinergics.Excessive stimulation of mesocortical and mesolimbic dopaminergic pathways can lead to psychosis, which is the most common psychiatric problem related to dopaminergic treatment.In the face of a psychotic episode, antiparkinsonian drugs which are not strictly necessary for motor control should be withdrawn. If this is not sufficient, levodopa dose should be reduced, considering the side effects that may occur. When the adjustment of antiparkinsonian treatment is not effective, neuroleptics, especially quetiapine or clozapine, should be administered. In a recent study, pimavanserin, a serotonin 5-HT2 antagonist, was associated with approximately 35% lower mortality than atypical antipsychotic use during the first 180 days of treatment in community-dwelling patients.Medication should always be tailor-made to suit each patient and we usually have to resort to lowering or withdrawing the dopaminergic medication.Disclosure of InterestNone Declared

Pharmacogenomics-a New Frontier for Individualized Treatment of Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease with a significant public health burden. It is characterized by the gradual degeneration of dopamine neurons in the central nervous system. Although symptomatic pharmacological management remains the primary therapeutic method for PD, clinical experience reveals significant inter-individual heterogeneity in treatment effectiveness and adverse medication responses. The mechanisms behind the observed interindividual variability may be elucidated by investigating the role of genetic variation in human-to-human variances in medication responses and adverse effects. This review aims to explore the impact of gene polymorphism on the efficacy of antiparkinsonian drugs. The identification of factors associated with treatment effectiveness variability might assist the creation of a more tailored pharmacological therapy with higher efficacy, fewer side outcomes, and cheaper costs. In this review, we conducted a thorough search in databases such as PubMed, Web of Science, and Google Scholar, and critically examined current discoveries on Parkinson's disease pharmacogenetics. The ethnicity of the individuals, research methodologies, and potential bias of these studies were thoroughly compared, with the primary focus on consistent conclusions. This review provides a summary of the existing data on PD pharmacogenetics, identifies its limitations, and offers insights that may be beneficial for future research. Previous studies have investigated the impact of gene polymorphism on the effectiveness and adverse effects of levodopa. The trendiest genes are the COMT gene, DAT gene, and DRD2 gene. However, limited study on other anti-Parkinson's drugs has been conducted. Therefore, In order to develop an individualized precision treatment for PD, it is an inevitable trend to carry out multi-center, prospective, randomized controlled clinical trials of PD pharmacogenomics covering common clinical anti-PD drugs in large, homogeneous cohorts.

A case of drug induced dizziness in a patient on anti-Parkinson drugs

Parkinson’s disease (PD) is the second most common age-related neurodegenerative disease, exceeded only by Alzheimer’s disease. Clinically, PD is characterized by resting tremor, rigidity (stiffness), bradykinesia (slowing), and gait dysfunction with postural instability. These are known as the classical or “cardinal” features of the disease. Levodopa remains the most effective symptomatic treatment for PD and the gold standard against which new therapies are compared. Levodopa is routinely administered in combination with a peripheral decarboxylase inhibitor to prevent its peripheral metabolism to dopamine and the development of nausea, vomiting, and orthostatic hypotension. The major concern with levodopa is that chronic levodopa treatment is associated with the development of motor complications, nausea and dizziness in the large majority of patients. We are here reporting a case of Syndopa plus (Levodopa+Carbidopa) induced dizziness in a 76 years old male patient on anti- parkinsonism treatment. The causality assessment was done by Naranjo scale. The causality of Syndopa plus in the case was “probable” as per Naranjo scale. The patient was managed by reducing the dose of Syndopa plus to the half of it’s initial dose. The case was recorded properly in adverse drug reaction reporting form and was sent to nearby ADR (adverse drug reaction) monitoring centre.

Sex differences in factors influencing hospital-acquired pneumonia in schizophrenia patients receiving modified electroconvulsive therapy.

Sex differences may be presented in the clinical features or symptoms of schizophrenia patients but also affect the occurrence of hospital-acquired pneumonia (HAP). Modified electroconvulsive therapy (mECT) is a common treatment method for schizophrenia, used in combination with antipsychotics. This retrospective research explores the sex difference in HAP affecting patients with schizophrenia who have received mECT treatment during hospitalization. We included schizophrenia inpatients treated with mECT and antipsychotics between January 2015 and April 2022. Blood-related and demographic data collected on admission were analyzed. Influencing factors of HAP in male and female groups were assessed separately. A total of 951 schizophrenia patients treated with mECT were enrolled in the study, including 375 males and 576 females, of which 62 patients experienced HAP during hospitalization. The risk period of HAP in these patients was found to be the first day after each mECT treatment and the first three sessions of mECT treatment. Statistically significant differences in the incidence of HAP were identified in male vs. female groups, with an incidence in men about 2.3 times higher than that in women (P < 0.001). Lower total cholesterol (Z = -2.147, P = 0.032) and the use of anti-parkinsonian drugs (χ2 = 17.973, P < 0.001) were found to be independent risk factors of HAP in male patients, while lower lymphocyte count (Z = -2.408, P = 0.016), hypertension (χ2 = 9.096, P = 0.003), and use of sedative-hypnotic drugs (χ2 = 13.636, P < 0.001) were identified in female patients. Influencing factors of HAP in schizophrenia patients treated with mECT have gender differences. The first day after each mECT treatment and the first three sessions of mECT treatment were identified to have the greatest risk for HAP development. Therefore, it would be imperative to monitor clinical management and medications during this period according to these gender differences.

Treatment of Parkinson’s disease with piribedil: Suggestions for clinical practices

With rapidly growing rates of prevalence, disability, and mortality, Parkinson’s disease (PD) has become a global healthcare burden. Increasing elderly population increases the incidence of neurodegenerative diseases in China. Hence, PD poses a huge burden to Chinese economic and healthcare system. PD is a movement disorder that affects the motor and nonmotor functions. Dopamine agonists are used in the management of PD. Piribedil is an antiparkinsonian drug and piperazine derivative, which acts as D2/D3 receptor agonist. Piribedil is one of the non-ergot dopamine receptor (DR) agonists and has been used in China for many years as monotherapy or in combination with levodopa. In this paper, we present a review of clinical application of piribedil, management of adverse events, and drug interactions, and discuss the results of clinical trials of piribedil on motor and non-motor symptoms of PD.

Differences in Parkinson's disease treatment between neurology and other departments in Japan

AbstractBackgroundParkinson's disease is common in elderly people and is treated in the neurology department as well as in other departments. Recently, treatment options for Parkinson's disease have expanded; this complicates selection of the best treatment regimen.AimTo investigate the change in Parkinson's disease treatment in Japan and assess the differences in prescriptions between neurology and other departments.MethodsPatients with Parkinson's disease who were prescribed levodopa and/or non‐ergot dopamine agonist were analyzed in an observational study using a Japanese claims database (April 2008–July 2017). The percentage of patients receiving each antiparkinsonian drug and the proportion of patients prescribed levodopa alone, levodopa plus non‐ergot dopamine agonist, and non‐ergot dopamine agonist alone were calculated by year (2010–2017) and department (neurology or other departments).ResultsWe identified 50,408 patients (mean [standard deviation] age: 73.4 [10.3]), including 25,231 (71.3 [10.1]) and 25,177 (75.5 [10.2]) patients who received their initial Parkinson's disease treatment in neurology and other departments, respectively. The popularity of levodopa alone and levodopa plus non‐ergot‐ dopamine agonist varied in the neurology department, while levodopa alone was the most popular treatment choice in all investigated years in other departments.ConclusionsThe number of patients initially treated for Parkinson's disease in neurology department, relative to other departments, did not differ. The treatment changes were observed in the neurology department but not in other departments.

Machine Learning Study: From the Toxicity Studies to Tetrahydrocannabinol Effects on Parkinson's Disease

Aim: Investigating molecules having toxicity and chemical similarity to find hit molecules. Methods: The machine learning (ML) model was developed to predict the arylhydrocarbon receptor activity of anti-Parkinson's and US FDA-approved drugs. The ML algorithm was a support vector machine, and the dataset was Tox21. Results: The ML model predicted apomorphine in anti-Parkinson's drugs and 73 molecules in FDA-approved drugs as active. The authors were curious if there is any molecule like apomorphine in these 73 molecules. A fingerprint similarity analysis of these molecules was conducted and found tetrahydrocannabinol (THC). Molecular docking studies of THC for dopamine receptor 1 (affinity=-8.2kcal/mol) were performed. Conclusion: THC may affect dopamine receptors directly and couldbe useful for Parkinson's disease.