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levodopa + benserazide (Madopar HBS / Levopar Plus / Prolopa)

✓ Approved

Roche · DDC · 小分子

什么是 levodopa + benserazide？

levodopa + benserazide 是一种小分子，由Roche研发。该药已获批，用于治疗相关适应症，给药途径：Oral (PO)。

药物档案

商品名Madopar HBS, Levopar Plus, Prolopa
公司Roche
药物类别小分子
分子靶点DDC
给药途径Oral (PO)
状态Approved
来源： ClinicalTrials.gov, Roche

作用机制

分子靶点

levodopa + benserazide 作用于 1 个分子靶点：

DDCdopa decarboxylase (AADC)
需要更深入的分析？Noah AI 可解释复杂机制并与同类药物比较。

治疗适应症

levodopa + benserazide 针对 1 个适应症，涉及 1 个治疗领域。

治疗领域疾病/病症分期
Nervous system disordersParkinson's disease✓ Approved

相关研究文献

PubMedNeurology2026-09-09

Levodopa Use and Characteristics of Freezing-of-Gait in Patients With Parkinson Disease in the NS-Park and PPMI Cohorts.

Barbosa Raquel R, Bastos Paulo P, Rascol Olivier O, Corvol Jean-Christophe JC et al.

Recent reports have suggested that levodopa exposure may contribute to freezing of gait (FOG), but this relationship remains controversial because of confounding by disease severity and duration. Our goal was to assess the relationship between levodopa use and FOG incidence and severity. We studied 2 prospective, multicentric cohorts: NS-Park and Parkinson's Progression Markers Initiative (PPMI). Patients with ≥2 visits were selected. Three nested subcohorts were defined based on disease duration, baseline FOG, and levodopa exposure. FOG was assessed using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II 2.13. Analyses included mixed-effects ordered logistic regression to evaluate FOG severity and Kaplan-Meier and Cox proportional hazards models to assess incident FOG. Models adjusted for disease duration, Hoehn and Yahr (H&Y) stage, and MDS-UPDRS Part III scores. A total of 25,602 patients with Parkinson disease from the NS-Park (mean age 68.3 ± 29.1, 42% female) and 1,441 from the PPMI (mean age 62.9 ± 9.8, 37% female) cohorts were included. In unadjusted analyses with the NS-Park cohort, levodopa use was associated with higher FOG severity and incidence, but this association was no longer statistically significant in the PPMI cohort. In mixed-effects ordinal logistic regression models adjusting for disease duration/severity, levodopa status showed a nonsignificant effect size on FOG (NS-Park odds ratio [OR] 1.84, 95% CI 0.94-3.61, p = 0.074; PPMI OR 0.76, 95% CI 0.38-1.51, p = 0.430), while disease duration (NS-Park OR 4.4, 95% CI 3.01-6.29, p = 6.0e-15; PPMI OR 6.97, 95% CI 5.05-9.63, p = 4.7e-32), Hoehn & Yahr stage (NS-Park OR 6.8, 95% CI 3.52-13.08, p = 1.059e-08; PPMI OR 1.5, 95% CI 0.96-2.22, p = 0.073), and MDS-UPDRS-III score (NS-Park OR 1.85, 95% CI 1.38-2.49, p = 4.34e-05; PPMI OR 2.00, 95% CI 1.67-2.39, p = 2.4e-14) were independently associated with greater FOG severity. No statistically significant association was observed between future levodopa exposure and de novo FOG incidence. In turn, FOG incidence was driven by the H&Y (NS-Park: hazard ratio [HR] 1.94, 95% CI 1.68-2.23; PPMI: HR 1.78, 95% CI 1.47-2.17) and MDS-UPDRS III (NS-Park: HR 1.40, 95% CI 1.07-1.83; PPMI: HR 1.26, 95% CI 1.17-1.36). No significant or consistent association between levodopa exposure and FOG severity or incidence was observed after adjustment for disease duration and severity, with the effect estimates significantly attenuated despite residual uncertainty.

PMID 42715510
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PubMedAmerican journal of medical genetics. Part A2026-09-09

Severe Headbanging Responsive to Levodopa in a Child With FOXP1 Syndrome.

Veale Pamela P, Tiessen Christopher C, Gnanakumar Vithya V

We report a 9-year-old female with FOXP1 syndrome due to a de novo in-frame deletion in the FOXP1 gene. The child has a severe neurodevelopmental disorder including global developmental delay and autism spectrum disorder. At age 2, she developed severe headbanging, which was progressive and did not respond to multidisciplinary, behavioral management strategies or to multiple medication treatments. Although repetitive behaviors are frequent in patients with FOXP1 variants, severe and intractable headbanging has not been reported to date. Levodopa/carbidopa was prescribed at age 7 due to progressive foot dystonia and contracture development. This treatment was not clearly beneficial for the dystonia and foot position, but immediate improvement in headbanging was observed and the response sustained for over 19 months. The FOXP1 gene codes for a transcriptional regulator protein that has been shown to regulate the development of brain and spinal motor neurons, and some evidence has linked FOXP1 to the differentiation of midbrain dopaminergic neurons via the homeobox protein PITX3, thus providing a potential mechanism for the observed benefit. This case report may provide expansion of the behavioral phenotype associated with FOXP1 variants and suggests avenues for further animal research and/or clinical trial of levodopa in individuals with FOXP1 variants.

PMID 42711896
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PubMedMovement disorders clinical practice2026-09-09

Dissociable Handwriting Domains in Parkinson's Disease?

Cetin Beyza Nur BN, Comoglu Selcuk S, Ulker Aycan Cemil AC, Onder Halil H

Handwriting abnormalities in Parkinson's disease (PD) extend beyond classical micrographia and may involve multiple graphomotor domains with distinct clinical and mechanistic correlates. To investigate whether distinct handwriting domains demonstrate dissociable relationships with differential diagnostic performance, cognitive function, motor severity, and dopaminergic responsiveness. We evaluated tablet-based handwriting kinematics in 60 PD and 58 essential tremor (ET) patients using a standardized sequential writing task performed on a digital tablet. Spatial, temporal, pressure-related, and decrement measures were analyzed together with cognitive performance, levodopa responsiveness, and multivariate clinical associations. Compared with ET, PD patients demonstrated significantly smaller final-segment handwriting area (991 ± 582 vs. 1623 ± 710, p < 0.001, d = 0.97), lower mean pressure (0.69 ± 0.17 vs. 0.81 ± 0.13, p < 0.001, d = 0.80), and higher prevalence of progressive reduction ≥10% (58.3% vs. 10.3%, OR = 12.13). Area ratio showed the strongest univariate discriminative performance (AUC = 0.814), whereas multivariate regression identified final-segment area (β = -0.52, p < 0.001) and mean pressure (β = -0.31, p = 0.003), but not decrement measures, as independent predictors of PD. Within the PD group, smaller final-segment handwriting area independently correlated with greater motor severity (β = -0.39, p = 0.004) and poorer visuospatial performance (β = +0.27, p = 0.028), whereas pressure-related measures demonstrated greater levodopa responsiveness. In contrast, decrement measures showed comparatively weak independent associations with motor severity, cognition, and dopaminergic responsiveness. Handwriting abnormalities in PD appear multidimensional and demonstrate partially dissociable relationships with motor severity, visuospatial performance, levodopa responsiveness, and differential diagnostic performance. These findings suggest that different handwriting domains may reflect complementary aspects of graphomotor dysfunction rather than a unitary phenomenon.

PMID 42712204
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PubMedMovement disorders clinical practice2026-09-09

JAK2 Variant and Parkinsonian Syndromes: Coincidence or Pathophysiological Link?

Jurado Elena Ardila EA, Bavdhankar Koustubh K, Garg Divyani D, Magrinelli Francesca F et al.

JAK2 variants are a hallmark of myeloproliferative neoplasms (MPNs), including polycythemia vera and essential thrombocythemia. These disorders are often associated with thrombotic and inflammatory complications. From a movement disorder perspective, chorea is a rare but well-recognized neurological occurrence in this context, whereas parkinsonism has received limited attention. To describe parkinsonian phenotypes in patients with JAK2-mutated MPNs and explore possible pathophysiological links. We identified five patients with a JAK2-mutated MPNs and parkinsonism and reviewed their demographic and clinical features, neuroimaging, and levodopa response. Parkinsonian phenotypes were heterogeneous, including Parkinson's disease (n = 2), atypical parkinsonism (n = 1), motor neuron disease with parkinsonism (n = 1), and chorea followed by parkinsonism (n = 1). The latter patient developed parkinsonism approximately 22 months after onset of generalized chorea. When available (n = 2), DaTscan was abnormal. Levodopa responsiveness was variable. Although JAK2-mutated MPNs and parkinsonism may coexist coincidentally, recent evidence suggests plausible pathophysiological links, including vascular, inflammatory, immune-mediated, and treatment-related mechanisms.

PMID 42712083
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PubMedFood and waterborne parasitology2026-09-09

Trichinella spiralis infection remodels intestinal neurotransmitter metabolism during LPS-induced systemic inflammation.

Sun Ruohang R, Liu Yi Y, Lv Qingbo Q, Shang Kaimeng K et al.

Parasitic helminths can modulate host inflammatory responses, but whether this regulation involves remodeling of the intestinal neurochemical environment remains unclear. Here, we investigated whether Trichinella spiralis infection alters intestinal neurotransmitter-related metabolism during lipopolysaccharide (LPS)-induced systemic inflammation. In this study, we established an LPS-induced inflammatory model and a T. spiralis-infection with LPS challenge model. At 14 days after infection, mice were challenged with LPS, and inflammatory responses and duodenal neurotransmitter-related metabolites were assessed. T. spiralis infection reduced serum TNF-α and IL-1β levels and alleviated LPS-induced lung pathology. Targeted LC-MS/MS profiling revealed treatment-specific neurochemical signatures in duodenal tissues. Under basal conditions, T. spiralis infection increased histamine levels and reduced norepinephrine, 5-hydroxyindoleacetic acid, and xanthurenic acid. During LPS challenge, prior T. spiralis infection was associated with increased dopamine, epinephrine, levodopa, 5-hydroxytryptophan, histamine, and tyramine compared with LPS challenge alone. These changes suggest that T. spiralis infection remodels tyrosine-, histidine-, and tryptophan-related neurochemical pathways in the intestine. Receiver operating characteristic analysis further identified several metabolites that discriminated LPS-challenged mice from T. spiralis-infected, LPS-challenged mice, although these candidate signatures require validation in larger independent cohorts. Together, our findings indicate that intestinal neurochemical remodeling may represent a previously underappreciated component of helminth-associated anti-inflammatory regulation.

PMID 42713351
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PubMedMetabolic brain disease2026-09-09

Therapeutics candidates and repurposing strategies to target parkinson's disease pathology: current evidence and future directions.

Dhanush Yarava Y, Nizamuddin N D ND, Neelima Satrasala S, Kalpana S S et al.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder worldwide, affecting over 8.5 million individuals globally. Its pathophysiology is multifactorial, encompassing progressive loss of dopaminergic neurons in the substantia nigra, accumulation of misfolded alpha-synuclein, mitochondrial dysfunction, oxidative stress, neuroinflammation, and impaired proteostasis. Despite decades of research, current treatments remain predominantly symptomatic, with levodopa and dopamine replacement therapies failing to halt neurodegeneration. Given the high cost and low success rate of de novo drug development, both repurposed approved drugs and mechanistically targeted investigational therapeutics have emerged as promising approaches as a strategically rational alternative that leverages established safety profiles, known pharmacokinetics, and abbreviated regulatory pathways. This review aimed to comprehensively examine the current evidence for repurposed drugs, clinically investigated therapeutic candidates, and repositioning strategies targeting the principal pathological hallmarks of Parkinson's disease: (1) alpha-synuclein aggregation and propagation, (2) oxidative stress, (3) neuroinflammation, (4) mitochondrial dysfunction, (5) lysosomal and proteasomal dysfunction, and (6) dopaminergic neurodegeneration. The review further sought to identify recurring translational challenges, propose mechanistic frameworks for rational combination therapy, and outline future directions for trial design and biomarker integration. A narrative review of published preclinical studies, clinical trials, and recent literature was conducted, focusing on repurposed compounds with mechanistic plausibility and evidence of CNS penetration relevant to PD pathology. Evidence from Phase 1-3 clinical trials and post-mortem neuropathological analyses was synthesised across each pathological hallmark. Compounds were evaluated for mechanistic specificity, pharmacokinetic suitability, and clinical translation status. Across six pathological hallmarks, repurposed agents showed disease-relevant activity, with variable clinical translation. Ambroxol, a GCase pharmacological chaperone, achieved ~ 30-34% brain penetration, increased cerebrospinal fluid alpha-synuclein in a Phase 2 trial (n = 17) regardless of GBA mutation status, and is now in Phase 3 (ASPro-PD, n = 330). N-acetylcysteine restored depleted brain glutathione, scavenged reactive oxygen species, preserved VMAT2 and tyrosine hydroxylase expression, and improved motor outcomes, with positive dopamine transporter imaging in clinical studies. Doxycycline, a BBB-penetrant antibiotic, suppressed microglial MMP-3 and MMP-9 and downregulated TNF-α, IL-1β, iNOS, and COX-2 in preclinical PD models. Metformin and its mitochondria-targeted analog Mito-Met activated AMPK signalling and reversed mitochondrial dysfunction in PD models; however, Mito-Q10 failed in a one-year clinical trial, highlighting that ~ 70% of dopaminergic neurons are already lost at symptom onset, making intervention timing a decisive variable. For proteostatic dysfunction, the USP14 inhibitor IU1 enhanced both proteasomal and autophagic flux, though neurotoxicity above 200 µM limits its therapeutic window; BIIB122, a selective LRRK2 inhibitor, achieved CNS target engagement in Phase 1/2 trials, but its Phase 3 LIGHTHOUSE study was terminated, with Phase 2b LUMA ongoing. In dopaminergic neurodegeneration, GLP-1 receptor agonists produced divergent outcomes: Exenatide-PD3 (n = 231) showed no benefit over placebo, whereas LixiPark demonstrated reduced motor progression in early-stage PD, revealing that mechanistic equivalence does not guarantee clinical equivalence across heterogeneous patient populations. Drug repurposing represents a viable and strategically advantageous approach to targeting PD pathophysiology. Repurposed compounds, including ambroxol, N-acetylcysteine, doxycycline, metformin, and GLP-1 receptor agonists, demonstrate engagement with disease-relevant mechanisms and, in several cases, preliminary evidence of clinical activity. However, a recurring translational challenge is the timing of therapeutic intervention: with approximately 70% of dopaminergic neurons already lost at symptom onset, even mechanistically sound agents may fail if administered too late. Divergent GLP-1 trial outcomes underscore that mechanistic equivalence does not guarantee clinical equivalence, and that disease-stage heterogeneity is a critical confounder. Future priorities must include: (i) precision stratification by genetic profile (e.g., GBA and LRRK2 variants); (ii) combination therapies targeting multiple interconnected hallmarks simultaneously; (iii) development of validated fluid and neuroimaging biomarkers for early-stage patient selection; and (iv) adaptive trial designs that accommodate heterogeneity across the PD population. Integration of computational tools network pharmacology, machine learning, and systems biology with biomarker-defined clinical enrichment will be essential for accelerating repurposed candidates toward meaningful disease modification.

PMID 42714656
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