Xadago (safinamide) / Meiji Seika, Eisai, Valeo Pharma, Zambon, Newron, Sun Pharma, Supernus Pharma - LARVOL DELTA

Chemometric-assisted spectrophotometric approach for stability assessment of safinamide and its synthetic precursor in antiparkinsonian formulation with sustainability profiling. (PubMed, Sci Rep) - "Furthermore, these methods can be used as a substitute for HPLC in quality control laboratories when multiple samples need to be analyzed within a short timeframe. Finally, various sustainability assessment tools were utilized to evaluate and measure the environmental background of the established methods."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease

A computational-based search of natural product derived multi-target ligands for the management of Alzheimer's and Parkinson's disease using structure-based pharmacophore modelling, virtual screening, MD docking, free energy analysis, ADMET profiling and DFT studies. (PubMed, SAR QSAR Environ Res) - "Four hits (N1-N4) displayed superior binding affinities relative to reference drugs donepezil (DNP) and safinamide (SAF). Additionally, density functional theory (DFT) studies provided insights into the electronic characteristics and reactivity of top hits. Overall, this integrated in silico approach emphasized the potential of natural scaffolds as sustainable multi-target-directed ligands (MTDLs) for AD and PD therapeutics."

Journal • Alzheimer's Disease • CNS Disorders • Movement Disorders • Pain • Parkinson's Disease • DRD2

Nocturnal Hypokinesia and Early Morning OFF in Parkinson's Disease: State-of-the-Art and Systematic Review of Treatment Availability. (PubMed, Curr Neurol Neurosci Rep) - "Pharmacologic treatments include standard and sustained-release levodopa, dopamine agonists (rotigotine, ropinirol, pramipexole, and apomorphine), MAO-B inhibitors (rasagiline, safinamide), COMT inhibitors (opicapone), and rescue therapies like inhaled or dispersible levodopa or apomorphine injection. For mild, disturbing symptoms in early PD, inhaled or dispersible levodopa or apomorphine injection are advised. In moderate to advanced stages, treatment options include long-acting dopamine agonists, MAO-B inhibitors, sustained-release levodopa, or COMT inhibitors selected based on factors such as daytime motor symptoms, and non-motor symptoms."

Journal • Review • CNS Disorders • Movement Disorders • Parkinson's Disease • COMT

Effects of MAO-B and COMT inhibitors on sleep disturbances in Parkinson's disease: A network meta-analysis. (PubMed, J Mov Disord) - "However, in analyses of objective PSG data, safinamide was found to significantly increase REM sleep duration (mean difference, 5.70 [95% CI, 2.26, 9.14]) and decrease wake time after sleep onset (mean difference, -10.20 [-19.38, -1.02]) compared to rasagiline and placebo. Given the limited number and small scale of available trials, the overall evidence should be interpreted cautiously. Nonetheless, this analysis highlights the need for further high-quality trials focused on sleep outcomes to guide personalized use of MAO-B and COMT inhibitors for sleep disturbances in PD."

Journal • Retrospective data • CNS Disorders • Movement Disorders • Parkinson's Disease • Sleep Disorder • COMT

Inhibition of monoamine oxidase by fluorobenzyloxy chalcone derivatives. (PubMed, RSC Adv) - "Inspired by safinamide's pharmacophoric features, the study focuses on designing, synthesizing, and evaluating a novel series of fluorinated benzyloxy chalcone derivatives as selective MAO-B inhibitors...Lead compounds were stabilized in protein-ligand complexes by the π-π stacking, which enabled them to bind to the active site of hMAO-B effectively. These results suggest that FBZ6 and FBZ13 are potent reversible selective MAO-B inhibitors, and they can be used as potential agents for the treatment of neurological disorders such as Alzheimer's diseases and PD."

Journal • Alzheimer's Disease • CNS Disorders • Movement Disorders • Neuroblastoma • Oncology • Parkinson's Disease • Solid Tumor

Evaluation of novel selective MAO-B inhibitors using immobilized enzymes on magnetic beads. (PubMed, J Pharm Biomed Anal) - "The assay was qualified with toloxatone and safinamide as reference inhibitors, yielding IC50 values of 3.42 ± 0.11 µM and 33.38 ± 1.38 nM, respectively. Additionally, a collection of terpenyl-benzohydrazides was screened, identifying PQM-244 (5c) as a selective MAO-B inhibitor (IC50 = 4.17 ± 0.082 µM) with a non-competitive inhibition mechanism (Ki = 2.28 ± 0.38 µM). These findings suggest that 5c (PQM-244) has significant potential to contribute to developing selective MAO-B inhibitors for Parkinson's disease therapy."

Journal • Cardiovascular • CNS Disorders • Depression • Movement Disorders • Parkinson's Disease • Psychiatry

Treatment Stability Across Different ADD-ON Therapies in Fluctuating Parkinson's Disease (MDS Congress 2025) - "Objective: This study investigates the efficacy and tolerability of selegiline (SL), rasagiline (RS), safinamide (SF), and opicapone (OP) in fluctuating PD patients, focusing on treatment stability and demographic influences. No single add-on therapy demonstrated superior stability, highlighting comparable efficacy across options. Sex significantly influenced therapy adjustments, with females requiring more frequent modifications. These findings underscore the importance of personalized treatment strategies in fluctuating PD management."

CNS Disorders • Movement Disorders • Parkinson's Disease • COMT

Safinamide as an Adjunct Therapy for Motor Symptoms and ON-Time Extension in Parkinson's Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials (MDS Congress 2025) - "Safinamide, at both 50 mg and 100 mg doses, significantly improves motor function and extends ON-time in PD patients with motor fluctuations. These findings support its role as an effective adjunct therapy to levodopa, warranting further investigation in long-term studies. Figure 1"

Retrospective data • Review • CNS Disorders • Movement Disorders • Parkinson's Disease

DIFFERENTIAL EFFECTS OF SAFINAMIDE TREATMENT (ACUTE, SUB-ACUTE AND CHRONIC) ON MICROGLIAL POLARIZATION IN A RAT MODEL OF TRANSIENT ISCHEMIC STROKE (WCN 2025) - "Post-stroke safinamide treatment attenuated neurological damage by switching microglial polarization towards anti-inflammatory M2 phenotype. Further exploration of safinamide through molecular studies can pave a way for repurposing it in ischemic stroke."

Preclinical • CNS Disorders • Movement Disorders • Parkinson's Disease • ARG1 • IL10 • IL1B • TGFB1 • TNFA

ADD-ON THERAPY WITH SAFINAMIDE AND AMANTADINE AMONG AMBULATORY FILIPINO PARKINSON'S DISEASE FLUCTUATORS: A SINGLE-CENTER EXPLORATORY STUDY (WCN 2025) - "Safinamide and Amantadine were effective adjunctive therapies to DRT in improving ON-times among ambulatory Filipino PD patients with motor fluctuations."

Clinical • CNS Disorders • Movement Disorders • Parkinson's Disease

SAFETY PROFILE OF SAFINAMIDE 100MG PER DAY IN KOREAN PATIENTS WITH PARKINSON'S DISEASE: A SAFETY ANALYSIS RESULTS FROM THE PROSPECTIVE MULTICENTER KEEP STUDY (WCN 2025) - "Most TEAEs occurred early in the treatment course, but stabilized over time. These results support the safety of continued use of safinamide 100mg/day and highlight the importance of early monitoring."

Clinical • CNS Disorders • Movement Disorders • Parkinson's Disease

EFFICACY OF SAFINAMIDE IN EARLY AND ADVANCED PARKINSON'S DISEASE: A PROSPECTIVE PILOT STUDY ON MOTOR AND NON-MOTOR SYMPTOM MANAGEMENT (WCN 2025) - "Our study highlights the potential efficacy of 50 mg safinamide on motor severity in PD across early and advanced stages, alongside its established role in managing motor fluctuations in advanced PD. To support the approval of safinamide as an adjuvant therapy for early-stage PD, further well-organized randomized controlled trials with larger sample sizes and diverse populations are necessary."

Clinical • Metastases • CNS Disorders • Movement Disorders • Parkinson's Disease

Add-on therapies to levodopa improve pain modulation in Parkinson's disease with motor fluctuations: A prospective cohort study. (PubMed, Parkinsonism Relat Disord) - "Pain processing is altered in pwPD, independently of subjective pain complaints. MAO-B inhibitors, particularly safinamide and rasagiline, appear to restore pain thresholds and improve QOL, supporting their role in managing pain in PD."

Journal • CNS Disorders • Fatigue • Mood Disorders • Movement Disorders • Pain • Parkinson's Disease • Psychiatry • COMT

Real-world data on the use of safinamide in a Parkinson's disease unit in Madrid, Spain (EAN 2025) - No abstract available

Clinical • Real-world • Real-world evidence • CNS Disorders • Movement Disorders • Parkinson's Disease

Long-term effectiveness of safinamide vs. rasagiline in Parkinson's disease: A real-world retrospective study (EAN 2025) - "Safinamide may offer a better treatment option for PD patients, with higher persistence rates, better comorbidity management, stabilized levodopa dosage, and reduced use of additional medications compared to rasagiline."

Real-world • Real-world evidence • Retrospective data • CNS Disorders • Movement Disorders • Parkinson's Disease

Eco-Friendly Simultaneous Quantification of Domperidone and Safinamide by Spectral Resolution using deconvoluted Synchronous Fluorescence: Application to Spiked Human Plasma. (PubMed, Luminescence) - "Sustainability of the current method was assessed using spider chart measure, green solvent selection tool, Analytical GREEnness Metric, Modified Green Analytical Procedure index, and Blue Applicability Grade Index. The proposed technique represents a simple, sensitive, and sustainable tool for routine analysis of this therapeutically significant drug pair."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease

Flecainide mediated sodium channel blockade enhances blood brain barrier integrity and promotes neuroprotection in neuroinflammation. (PubMed, Sci Rep) - "To evaluate the effects and understand the action mechanism of NaV blockers and MAO-B inhibitors (rasagiline, safinamide, flecainide and phenytoin) in neurological conditions, various techniques were used, including optical coherence tomography (OCT), optomotor response measurement (OMR), flow cytometry, histological evaluations, Evans blue assay, blood-brain barrier (BBB) permeability assay, western blot, proliferations assay, and gene expression analyses. The findings demonstrate induced neuroprotection and reduced disease progression, suggesting a novel therapeutic approach. Crucially, it reveals for the first time that NaV 1.5 channel blockade leads to neuroprotection primarily by affecting the BBB, a key factor in controlling immune cell migration, thus addressing a critical aspect of neuroinflammation."

Journal • CNS Disorders • Immunology • Inflammation • Multiple Sclerosis • Ocular Inflammation • Ophthalmology • Optic Neuritis

Design, synthesis, and biological evaluation of highly potent and selective hMAO-B inhibitors featuring a tetrahydrobenzo[f][1,4]oxazepine core. (PubMed, Eur J Med Chem) - "Among the synthesized compounds, ZM24 and ZM26, which possess the 2,3,4,5-tetrahydrobenzo[f][1,4]oxazepane core structure, exhibited a significant increase in both efficacy and isoform selectivity relative to safinamide. Subsequent biological assessments revealed that these two compounds act as reversible hMAO-B inhibitors, demonstrate substantial neuroprotective properties, and significantly improve motor dysfunction in MPTP-induced mouse models of PD, thereby reinforcing their potential therapeutic applications in the treatment of PD."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease

Targeting MAO-B selectivity: computational screening, docking, and molecular dynamics insights. (PubMed, SAR QSAR Environ Res) - "MD simulations (200 ns) and binding free energy calculations identified four promising compounds - ZINC21285023, ZINC79651118, ZINC58283019, and UNPD89644 (crotafuran E)- that exhibited stable binding and favourable interactions with key residues such as Cys172 and Tyr435. These compounds demonstrated performance comparable to or better than safinamide and are strong candidates for further experimental validation as selective MAO-B inhibitors."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease

Evaluation of the efficacy and cost-effectiveness of safinamide versus rasagiline: a systematic review. (PubMed, J Comp Eff Res) - "Limitations include reliance on clinical trial data and Spanish cost models. Future research incorporating real-world evidence is warranted."

Clinical • HEOR • Journal • Review • CNS Disorders • Movement Disorders • Parkinson's Disease

Effect of Safinamide on Sleep Quality in Patients With Parkinson's Disease (clinicaltrials.gov) - P4 | N=23 | Recruiting | Sponsor: Alain Kaelin | Trial completion date: Apr 2025 ➔ Apr 2026 | Trial primary completion date: Apr 2025 ➔ Apr 2026

Trial completion date • Trial primary completion date • CNS Disorders • Movement Disorders • Parkinson's Disease

Efficacy of Safinamide in Early-Stage Parkinson's Disease: A Pilot Evaluation of Motor Symptom Improvement. (PubMed, J Mov Disord) - No abstract available

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease

Use of safinamide for treatment of Parkinson disease: real-world data from Spain. (PubMed, Drugs Context) - "We reviewed a total of 36 reports covering around 2000 patients with PD. The reports confirm the safety and efficacy results obtained in clinical trials, showing a significant improvement in motor and non-motor fluctuations and enabling the dose of levodopa to be reduced, thus decreasing the likelihood of motor complications."

Clinical • Journal • Real-world evidence • Review • CNS Disorders • Movement Disorders • Parkinson's Disease

Green, innovative oral capsules of three anti-Parkinson's drugs: formulation, in vitro evaluation, and robust RP-HPLC validation. (PubMed, Anal Methods) - "However, the long-term use of LEV is often complicated by motor fluctuations and dyskinesias, necessitating adjunct therapies such as carbidopa (CAR) and safinamide (SAF) to enhance efficacy and reduce side effects. The greenness profile of the method was rigorously evaluated using the NEMI, AGP, ESA, AGREE, and MoGAPI methods. Furthermore, the blueness of the technique was studied using the BAGI method, confirming its alignment with green analytical chemistry principles."

Journal • Preclinical • CNS Disorders • Movement Disorders • Parkinson's Disease

Enzyme inhibitory activity of marine alkaloid aaptamines for neurodegenerative diseases: an in silico study. (PubMed, R Soc Open Sci) - "The top binding complexes (A12@MAOB, A24@COMT and A27@AChE) are simultaneously studied by molecular dynamics in water for 500 ns time-scale and compared with the references such as safinamide (SAG), tolcapone (TOL) or donepezil (DON). The van der Waals interactions contribute more strongly to enzyme binding than the electrostatic energy. The study results suggest that A27 (lowest binding energy, -170.42 ± 14.24 kJ mol-1) is the most prominent aaptamine candidate for the treatment of NDs."

Journal • CNS Disorders • Pain • COMT