Antiparkinsonian Drugs Research Articles

Kinetic Basis for the Design of Azobenzene-Based Photoswitchable A2a Adenosine Receptor Ligands.

Photoisomerization of ligands is a key process in the field of photopharmacology. Thus, the kinetics and efficiency of this initial photoreaction are of great importance but can be influenced by the molecular environment of the binding pocket and the resulting confinement of the reaction pathway. In this study, we investigated the photoisomerization of an azobenzene derivative of the anti-Parkinson's drug istradefylline. To identify the impact of the binding pocket, the ligand was examined in solution and bound to its target protein, the A2a adenosine receptor (A2aR), belonging to the family of G protein-coupled receptors (GPCRs). Although the overall efficiency of isomerization is reduced when the ligand is bound, the initial photoreaction experiences little influence from the binding pocket. However, protein-coupled motion promotes a longer-lived excited-state population and thus leads to a reduction in efficiency. The results provide the kinetic basis for a photoswitchable GPCR ligand and demonstrate the influence of the binding pocket on fundamental photochemistry.

Spectral resolution techniques for the simultaneous spectrophotometric determination of anti-Parkinson drugs in their combined pharmaceutical dosage form and biological sample based on multivariate calibration and absorbance subtraction methods

In this study, simultaneous determination of levodopa (LEV) and carbidopa (CBD) in binary mixtures, pharmaceutical formulation, and biological sample was conducted using the application of simple, fast, sensitive, and accurate UV-spectrophotometry in combination with chemometrics methods. The first method is net analyte signal (NAS) based on the multivariate calibration methods. The limit of detection (LOD) and limit of quantification (LOQ) were 0.9758, 0.7633 µg/mL and 2.956, 2.313 µg/mL over the linear range of 5–40 and 0.5–20 µg/mL for LEV and CBD, respectively. In the NAS approach, the mean recovery values of mixtures were 100.12 % for LEV and 99.65 % for CBD, where root mean square error (RMSE) values were 0.0106 and 0.0141 for LEV and CBD, respectively. The second method is absorbance subtraction (AS) based on the absorption factor technique for analyzing the isosbestic point. This model was constructed at an isosbestic point of 261 nm in the range of 5–40 and 0.5–20 µg/mL with coefficient determination (R2) of 0.9985 and 0.9996 for LEV and CBD, respectively. AS method could estimate LEV and CBD with LOD values of 1.924 and 0.5657 μg/mL and LOQ values of 5.833 and 1.714 μg/mL, respectively. The recovery percentage was between 91.50 % to 104.60 % with RMSE of 0.1455 for LEV and 92.00 % to 106.66 % with RMSE of 0.2508 for CBD. The introduced approaches have the benefit of concurrent analysis of the mentioned components without any pretreatment. Statistical comparison of the results of real sample analysis with high-performance liquid chromatography (HPLC) did not show a significant difference. These methods can replace HPLC in quality control laboratories when fast, precise, and low-cost analysis is needed.

A novel stability-indicating chromatographic quantification of the antiparkinsonian drug safinamide in its pharmaceutical formulation employing HPTLC densitometry and ion-pair HPLC–DAD

Parkinson's disease (PD) emerges as a notable health concern among the elderly population. Safinamide mesylate (SAF) is a novel and emerging add-on therapy in PD treatment. The stability of innovative drug formulations and the development of appropriate stability-indicating methods are of great importance to modern pharmaceutical analysis. The current work has established novel comprehensive stability-indicating chromatographic approaches, HPTLC coupled with densitometric quantification and HPLC–DAD, for the selective assay of SAF in pharmaceutical formulation along with its synthetic precursor impurity; 4-hydroxy benzaldehyde (4-HBD) in presence of its stress induced degradation products. The stability of SAF was investigated under different stress conditions. It was found that SAF is likely to undergo acid, base hydrolysis, and oxidative degradation. Using mass spectrometry and infrared spectroscopy, the structures of the forced degradation products were confirmed and elucidated. The dissolution behavior of Parkimedine® Tablets was also monitored in the FDA suitable medium. Multiple assessment tools were used to evaluate the environmental sustainability of the proposed methods and the reported one. The greenness tools included Complex-GAPI and AGREE metrics. In addition, the innovative concepts of "blueness" and "whiteness" evaluation were incorporated through the newly introduced BAGI and RGB12 algorithms, respectively.

Impact of Duration of Parkinsonism and Antiparkinsonian Drugs on Coagulation Parameters in Patients with Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disorder involving depletion of dopaminergic neurons. Pathogenetic mechanisms leading to striatonigral degeneration are debatable. Chronic inflammation is proposed as one of the mechanisms. In any disease with underlying inflammation, immune system mediators called cytokines are released, leading to a procoagulant state. Our aim was to study the coagulation parameters in patients with PD and find their correlation with disease duration and antiparkinsonian drugs. This cross-sectional study was conducted between January 2021 and December 2021 in a tertiary care center. Sixty-eight patients with PD were subcategorized based on disease duration (<5 and ≥5 years), number of antiparkinsonian drugs (one drug and ≥2 drugs), and levodopa equivalent daily dose (LEDD; <350 and ≥350 mg). Hemoglobin (Hb), prothrombin time (PT), fibrinogen, bleeding time, and platelet aggregation study with adenosine diphosphate and collagen were assessed. In our cohort of 68 patients, 53 were men and 15 were women. Mean disease duration was 5.97 ± 4.37 years. Hb was negatively associated with LEDD (P = 0.012) and duration of the disease (P = 0.02). Similarly, PT was negatively associated with disease duration (P = 0.041) and number of antiparkinsonian drugs (P = 0.03). LEDD showed a positive association with collagen-induced platelet aggregation (P = 0.03). In our study, patients using multiple antiparkinsonian drugs and higher LEDD were observed to have a prothrombotic state. Further studies are needed to confirm these findings.

Comprehensive data for studying serum exosome microRNA transcriptome in Parkinson’s disease patients

Parkinson’s disease (PD), the second most prevalent neurodegenerative disorder, was classically attributed to alpha-synuclein aggregation and consequent loss of dopaminergic neurons in the substantia nigra pars compacta. Recently, emerging evidence suggested a broader spectrum of contributing factors, including exosome-mediated intercellular communication, which can potentially serve as biomarkers and therapeutic targets. However, there is a remarkable lack of comprehensive studies that connect the serum exosome microRNA (miRNA) transcriptome with demographic, clinical, and neuroimaging data in PD patients. Here, we present serum exosome miRNA transcriptome data generated from four cohort studies. Two of these studies include 96 PD patients and 80 age- and gender-matched controls, with anonymised demographic, clinical, and neuroimaging data provided for PD patients. The other two studies involve 96 PD patients who were evaluated both before and after one year of treatment with rasagiline, a widely prescribed anti-parkinsonism drug. Together, the datasets provide a valuable source for understanding pathogenesis and discovering biomarkers and therapeutic targets in PD.

Explore the Role of the Sphingosine-1-Phosphate Signalling as a Novel Promising Therapeutic Target for the Management of Parkinson's Disease.

Sphingosine-1-phosphate (S1P) is a cellular signalling molecule derived from sphingosine, which is a pro-apoptotic sphingolipid. Sphingolipids control various cellular actions like growth, homeostasis, and stress-related responses. The main sources of S1P in our body are erythrocytes. S1P controls both cellular mediators and other second messengers intracellularly. The S1P receptor also helps in inflammatory and neuroprotective effects (required to manage of Parkinson's). A large number of anti-Parkinson drugs are available, but still, there is a need for more effective and safer drugs. S1P and its receptors could be targeted as novel drugs due to their involvement in neuro-inflammation and Parkinson's. The present review effort to explore the biological role of S1P and related receptors, for their possible involvement in PD; furthermore. Overall, S1P and other related metabolizing enzymes have significant therapeutic opportunities for Parkinson's disease along with other neurological disorders.

Improving the Efficiency of Luminescent Zn(II)-Modified N-Doped GOQD Nanomaterials in Parkinson's Disease Treatment: A Theoretical Mechanistic Framework Exploring Doping Effect.

Levodopa, a widely prescribed drug in Parkinson's disease treatment, stands as the foremost prodrug of dopamine. An affordable self-testing kit is utilized to monitor levodopa content in anti-parkinson drugs in human serum. A photoluminescent trinuclear Zn(II) complex [Zn3(L)2(κ1-OAc)2(κ2-OAc)2] has been synthesized, which cleaves into mononuclear ZC in aqueous solution. ZC was found to detect L-Dopa in Tris-HCl buffer, exhibiting a moderate decrease in PL-emission. The real-life utility of the ZC probe is limited, for its lower sensitivity (LOD 35.3 μM) and separation challenges. Therefore, an interface between homogeneous and heterogeneous supports has been explored, leading to the strategic development of NGOZC, where ZC was grafted onto NGOQD (Graphene oxide quantum dots). This material enables naked- eye detection under both ambient and UV light with color change from bright cyan to green, followed by dark. The nitrogen doping effect was investigated by several comparative investigations involving the synthesis of ZC-grafted GOQD, leading to enhanced quenching performance. Steady-state and time-resolved fluorescence titration study, morphological analysis, and computational calculations have been performed to get insights into the sensing mechanism. To the best of our knowledge, this as-synthesized NGOZC (LOD 1.78 nM) represents a promising strategy and platform for applications in biosensors, especially for Parkinson's and Alzheimer's diseases.

The adsorption of amantadine antiparkinsonian drug on the B24N24 and Al24N24 nanoclusters: An investigation using the density functional theory

By employing the density functional theory (DFT), the present investigation studied the adsorption of an anti-Parkinson drug called Amantadine (AM) onto the nanoclusters of B24N24 and Al24N24. Through their –NH2 group, the molecules of Amantadine interacted with the B or Al head of the AlN(BN) nanoclusters, and it was found that the change in the free Gibbs energy was –32.3 (−27.2) kcal/mol. The increased dosage of Amantadine led to weaker AM/cluster interactions, which is attributable to the steric effect. The molecule of Amantadine was subjected to electrostatic adsorption onto the nanoclusters of AlN and charge transfer adsorption onto the nanoclusters of BN. The Amantadine adsorption led to a dramatic decrease from 4.47 eV to 3.63 eV in the work function of the AlN nanoclusters. As a result, the electron field emission improved. Thus, one may use AlN nanoclusters as an Φ-type chemical sensor for the detection of Amantadine molecules. The AM adsorption onto the BN nanoclusters resulted in noticeable HOMO destabilization and decreased HOMO-LUMO energy gap from 6.84 eV to 5.67 eV. Consequently, a great increase was observed in the electrical conductivity of the BN nanoclusters. As a result, one may use BN nanoclusters as a suitable candidate for manufacturing electronic sensors with the capability of detecting Amantadine.

Emission of 50-kHz ultrasonic vocalizations stimulated by antiparkinsonian dopaminomimetic drugs in hemiparkinsonian rats is associated with neuronal activation in subcortical regions that regulate the affective state

Dopamine replacement therapy (DRT) of Parkinson's disease (PD) may trigger non-motor complications, some of which affect hedonic homeostatic regulation. Management of iatrogenic alterations in the affective state in PD is unsatisfactory, partly because of the limitations in the experimental models that are used in the preclinical investigation of the neurobiology and therapy of these alterations. In this connection, we recently employed a new experimental approach consisting in measuring the emission of 50-kHz ultrasonic vocalizations (USVs), a marker of positive affect, in hemiparkinsonian rats treated with drugs used in the DRT of PD. To further strengthen our approach, we here evaluated how the acute and repeated (× 5, on alternate days) administration of apomorphine (2 mg/kg, i.p.) or L-3,4-dihydroxyphenilalanine (L-DOPA, 12 mg/kg, i.p.) modified the immunoreactivity for Zif-268, a marker of neuronal activation, in the nucleus accumbens (NAc), caudate-putamen (CPu) and medial prefrontal cortex (mPFC), which are brain regions that regulate emotional states and drugs' affective properties. Acute and repeated treatment with either apomorphine or L-DOPA stimulated the emission of 50-kHz USVs in hemiparkinsonian rats, and this effect was paired with increased Zif-268 immunoreactivity in the NAc and CPu, but not mPFC. These findings indicate that subcortical and cortical regions may differently regulate the emission of 50-kHz USVs in hemiparkinsonian rats treated with dopaminergic drugs used in the DRT of PD. Moreover, they provide further evidence that measuring 50-kHz USV emissions in hemiparkinsonian rats may be a relevant approach to investigate at the preclinical level the affective properties of antiparkinsonian drugs.

Deep brain stimulation for Parkinson’s disease: systematic review with meta-analysis and trial sequential analysis

ObjectiveTo assess the benefits and harms of deep brain stimulation for Parkinson’s disease.DesignSystematic review with meta-analysis and trial sequential analysis.Data sourcesCochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, Latin...

Impact of the Anticholinergic Burden on Disease-Specific Symptoms in Parkinsonian Syndromes.

Background: Anticholinergic adverse effects pose a relevant threat to patients, in particular elderly and cognitively impaired patients. Patients with Parkinsonian syndromes are especially at risk from anticholinergic adverse effects due to the often-required complex drug therapy. Aims: The aim of this study was to evaluate the potential effect of the anticholinergic burden on motor and non-motor symptoms in Parkinson's disease and atypical Parkinsonian syndromes. Methods: This cross-sectional, monocentric retrospective data analysis included 151 patients with Parkinson's disease (PD), 63 with progressive supranuclear palsy (PSP), and 36 with multiple system atrophy (MSA). The anticholinergic burden of patients' medications was determined using two established scores: the Anticholinergic Drug Scale (ADS) and the German Anticholinergic Burden Scale (GABS). These scores were compared between the different diseases and correlated with several disease-specific scores. Results: Anticholinergic burden was higher in patients with PD, in particular, compared to PSP. In the PD group, anticholinergic burden showed a weak correlation with almost all analyzed clinical scores and the number of administered drugs. The UMSARS I and II showed a significant correlation with the anticholinergic burden in MSA patients. In general, the GABS-measured anticholinergic burden was significantly higher compared to the ADS-measured. Conclusions: The calculated anticholinergic burden affected motor and non-motor symptoms in patients with various Parkinsonian syndromes poorly. Since the GABS also contains basic anti-parkinsonian drugs, this score tended to overestimate the anticholinergic burden in patients with Parkinsonian syndromes and, therefore, seemed less appropriate for this application.

Constipation: a neglected condition in older emergency department patients.

Constipation and fecal impaction are common issues with the potential for significant morbidity in older people presenting to the Emergency Department (ED). While many of these patients present with classical symptoms of constipation or fecal impaction, atypical presentations are also frequent. These atypical presentations may include paradoxical diarrhea, fecal incontinence, urinary retention or overflow incontinence, hyperactive or hypoactive delirium, anorexia/dysphagia, and syncope. In addition, various clinical conditions (such as dementia, Parkinson's disease, dehydration, and hypothyroidism) and medications (such as opiate analgesics, anticholinergics, diuretics, calcium channel blockers, anti-parkinsonian drugs, and oral iron supplements) are associated with constipation and should be considered during the diagnostic process in the ED. This narrative review specifically focuses on the prevalence, presentation, diagnoses, and management of constipation in older ED patients.

Time-Resolved Evaluation of L-Dopa Metabolism in Bacteria-Host Symbiotic System and the Effect on Parkinson's Molecular Pathology.

The gut microbiome influences drug metabolism and therapeutic efficacy. Still, the lack of a general label-free approach for monitoring bacterial or host metabolic contribution hampers deeper insights. Here, a 2D nuclear magnetic resonance (NMR) approach is introduced that enables real-time monitoring of the metabolism of Levodopa (L-dopa), an anti-Parkinson drug, in both live bacteria and bacteria-host (Caenorhabditis elegans) symbiotic systems. The quantitative method reveals that discrete Enterococcus faecalis substrains produce different amounts of dopamine in live hosts, even though they are a single species and all have the Tyrosine decarboxylase (TyrDC)gene involved in L-dopa metabolism. The differential bacterial metabolic activity correlates with differing Parkinson's molecular pathology concerning alpha-synuclein aggregation as well as behavioral phenotypes. The gene's existence or expression is not an indicator of metabolic activity is also shown, underscoring the significance of quantitative metabolic estimation in vivo. This simple approach is widely adaptable to any chemical drug to elucidate pharmacomicrobiomic relationships and may help rapidly screen bacterial metabolic effects in drug development.

Ecofriendly micellar mediated spectrofluorimetric method for ultrasensitive quantification of the antiparkinsonian drug safinamide in pharmaceutical formulation and spiked human plasma

A novel, highly sensitive and eco-friendly micellar-mediated spectrofluorimetric method was developed and validated for the determination of the novel antiparkinsonian drug safinamide mesylate in the presence of its related precursor impurity, 4-hydroxybenzaldehyde. The proposed approach relies on increasing the inherent fluorescence emission at 296 nm of safinamide, by forming hydrogen bonds between the mentioned drug and sodium dodecyl sulfate in the micellar system using 0.1 N HCl as a solvent, following excitation at 226 nm. A thorough investigation was conducted into the experimental factors affecting spectrofluorimetric behavior of the studied drug. A linearity plot of safinamide over the concentration range of 10.0–1000.0 ng/mL against the relative fluorescence intensities was established. The proposed method demonstrated excellent sensitivity down to the nano-gram level with detection and quantitation limits of 1.91 and 5.79 ng/mL, respectively. The studied drug was effectively determined in Parkimedine® Tablets. Furthermore, the proposed method allows for ultrasensitive quantification of safinamide in spiked human plasma, with satisfactory percentage recovery (98.97–102.28%). Additionally, the greenness assessment using the advanced green certificate classification approach, the complementary green analytical procedure index (Complex-GAPI), and the analytical GREEness metric approach (AGREE), along with the practicality check using the Blue Applicability Grade Index in addition to the all-inclusive overall whiteness evaluation using the RGB-12 model were carried out. The outcomes demonstrated the effectiveness and whiteness of the proposed technique. Clearly, the suggested approach has the advantages of being simple, requiring no pretreatment steps, and relying solely on direct measuring procedures.

Comparison of Pharmacokinetic Characteristics of Bilosomal Dispersion Versus Pure Solution of Oral Ropinirole Hydrochloride in Rats

Background: Ropinirole hydrochloride is a non-ergoline antiparkinson drug. It is a highly hydrophilic drug and classified as class III according to Biopharmaceutical Classification System with low absolute oral bioavailability of approximately 50% upon oral administration due to significant hepatic first-pass metabolism. Objective: to compare the pharmacokinetic parameters of Ropinirole, when administered orally in the form of a Ropinirole bilosomal dispersion in contrast to an oral Ropinirole solution. Methods: This study involved the use of twelve male Wistar rats, with an average weight of 220±11 g, and these rats were divided into two groups, comprising six rats each. A 1.1mg/kg doses of pure Ropinirole and Ropinirole bilosomes were administered orally through gavage after reconstituting in distilled water. Ropinirole was quantified in the rat's plasma using HPLC, subsequently establishing a spiked calibration curve with plasma samples and utilizing paracetamol as an internal standard. The statistics included mean values (± SD; n = 6) for pharmacokinetic parameters, with statistical significance assessed using a Student's t-test. Results: For the oral bilosomes, the values were 9.4±0.11 μg /ml for Cmax, 3±0.00 h for Tmax, and 55.56±2.12 μg h/ml for AUC0-24. In contrast, for the oral solution, the corresponding values were 7.2±0.14 μg/ml for Cmax, 1.5±0.00 h for Tmax, and 23.70±2.23 μg h/ml for AUC0-24. These parameters were significantly higher (P&lt;0.05) as compared with a pure drug solution. The comparative bioavailability of Ropinirole (AUC0-24 oral solution / AUC0-24 oral bilosomes ) is equal to 42.66%, which indicates the bioavailability of the oral RH solution was less than that of RH bilosomal dispersion. Conclusions: The use of nano vesicular carriers (bilosomes) shows significant potential as an effective delivery system for improving the oral bioavailability of ropinirole hydrochloride

Bridging Pharma and Sustainability: Green Electrochemical Analysis of Antiparkinsonian Drug in Pharmaceuticals and Plasma, Aligned with United Nations Goals via the NQS Index

This study presents a sustainable electrochemical investigation of pramipexole (PRA) in pharmaceuticals and human plasma, using cyclic and differential pulse voltammetry. Key parameters, including potential range, buffer pH, accumulation period, and scan rate were optimized, establishing efficient voltammetric methods for PRA analysis. The analytical range was 0.60–12.00 μg ml−1, with a detection limit of 0.14 μg ml−1 and a correlation coefficient of 0.9998. Recovery rates for PRA ranged from 98.60 ± 0.26% to 101.33 ± 0.38%, validating the methodology’s applicability in human plasma with an average recovery of 99.25 ± 0.45%. The study highlights the environmental sustainability of the developed voltammetric electrode, evaluated through SWOT analysis, and assesses the greenness impact using tools like Complementary Green Analytical Procedure Index (ComplexGAPI), Analytical greenness (AGREE) and Analytical greenness for sample preparation (AGREEprep). Significantly, this work aligns with numerous United Nations Sustainable Development Goals (UN-SDGs), specifically goals 3, 4, 5, 7, 9, 11, 12, 13, 14, 15, and 17, illustrating our commitment to sustainable pharmaceutical research. The sustainability of the method was further quantified using the newly introduced Need, Quality, Sustainability (NQS) index, demonstrating significant alignment with sustainable analytical practices.

A Recyclable Luminescent MOF Sensor for On-Site Detection of Insecticide Dinotefuran and Anti-Parkinson's Drug Entacapone in Various Environmental and Biological Specimens.

The monitoring and precise determination of pesticides and pharmaceutical drugs and their residues have become increasingly important in the field of food safety and water contamination issues. Herein, a fluorescent aluminium MOF-based sensor (1) was developed for the selective recognition of neonicotinoid insecticide dinotefuran and anti-Parkinson's drug entacapone. Guest-free MOF 1' exhibited ultra-fast response (<5 s) and ultra-low detection limits of 2.3 and 7.6 nM for dinotefuran and entacapone, which are lower than the previously reported MOF-based sensors. In the presence of other competitive analytes, great selectivity was achieved towards both analytes. The probe was recyclable up to five cycles. The sensing ability was explored towards entacapone in human serum, urine and dinotefuran in real soil, rice, honey samples, different fruits, vegetables, real water specimens and a wide range of pH media. A low-cost, handy MOF-based polymer thin-film composite (1'@PVDF-PVP) was developed for the on-site detection of dinotefuran and entacapone. Mechanistic studies involving analytical techniques and theoretical calculations suggested that FRET and PET are the probable reasons for entacapone sensing whereas IFE is responsible for dinotefuran detection. The entire work presents a low cost, multi-use photoluminescent sensor of entacapone and dinotefuran to address the environmental pollution.

Experimental pharmacokinetics of a new antiparkinsonian drug ADK-1113

The pharmacokinetics of a new antiparkinsonian drug ADK-1113 after single intravenous and intragastric administrations in mice at doses of 10 and 20 mg/kg was studied. The absolute bioavailability was 10.1–16.3 % that indicates on potential possibility of preparing a dosage form for oral administration.

Identification and structural elucidation of an oxidation product generated during stability studies of Cabergoline drug product

Cabergoline is a dopamine agonist with applications as anti-Parkinson drug and prolactin inhibitor. The cabergoline drug product Laktostop® 50 µg/mL is used in veterinary medicine for lactation suppression in cats and dogs e.g. during false pregnancy. Recently, during ongoing HPLC stability testing of Laktostop® 50 µg/mL a new oxidation product of Cabergoline was identified. A synthesis starting from Cabergoline was developed, followed by full characterization of the unknown impurity. Preliminary HPLC and LC-MS analyses indicated the unknown impurity as mono-oxygenated product of Cabergoline (Cabergoline N-oxide) that is presumably formed with oxygen by a radical mechanism. Thus, Cabergoline was treated with oxidizing agents such as m-chloroperoxybenzoic acid to afford the desired Cabergoline-N-oxide as a byproduct. After isolation by column chromatography, NMR and LC-MS-MS studies provided evidence that oxidation occurred at the N-allyl nitrogen of Cabergoline to form Cabergoline-N-oxide. © 1905 Elsevier Science. All rights reserved

Structure and Ligand Based Virtual Screening and MPO Topological Analysis of Triazolo Thiadiazepine-fused Coumarin Derivatives as Anti-Parkinson Drug Candidates.

Parkinson's disease (PD) is a debilitating condition that can cause locomotor problems in affected patients, such as tremors and body rigidity. PD therapy often includes the use of monoamine oxidase B (MAOB) inhibitors, particularly phenylhalogen compounds and coumarin-based semi-synthetic compounds. The objective of this study was to analyze the structural, pharmacokinetic, and pharmacodynamic profile of a series of Triazolo Thiadiazepine-fused Coumarin Derivatives (TDCDs) against MAOB, in comparison with the inhibitor safinamide. To achieve this goal, we utilized structure-based virtual screening techniques, including target prediction and absorption, distribution, metabolism, and excretion (ADME) prediction based on multi-parameter optimization (MPO) topological analysis, as well as ligand-based virtual screening techniques, such as docking and molecular dynamics. The findings indicate that the TDCDs exhibit structural similarity to other bioactive compounds containing coumarin and MAOB-binding azoles, which are present in the ChEMBL database. The topological analyses suggest that TDCD3 has the best ADME profile, particularly due to the alignment between low lipophilicity and high polarity. The coumarin and triazole portions make a strong contribution to this profile, resulting in a permeability with Papp estimated at 2.15 × 10-5cm/s, indicating high cell viability. The substance is predicted to be metabolically stable. It is important to note that this is an objective evaluation based on the available data. Molecular docking simulations showed that the ligand has an affinity energy of -8.075kcal/mol with MAOB and interacts with biological substrate residues such as Pro102 and Phe103. The results suggest that the compound has a safe profile in relation to the MAOB model, making it a promising active ingredient for the treatment of PD.