tolcapone / Generic mfg. - LARVOL DELTA

The therapeutic potential of COMT inhibition: cognition and beyond. (PubMed, Mol Psychiatry) - "Here, we review the evidence linking COMT with executive function, with a particular focus on human studies using the brain penetrant COMT inhibitor tolcapone...Taken together, these data are consistent with a model whereby COMT regulates PFC dopamine signaling to modulate top-down control over multiple aspects of behaviour. These findings suggest COMT inhibition as an attractive therapeutic approach in individuals with neuropsychiatric disorders associated with aspects of executive dysfunction."

Journal • Review • CNS Disorders • Mental Retardation • Psychiatry • COMT

Case Report: Five-year follow-up of leptomeningeal transthyretin amyloidosis (Ala45Thr) with CNS involvement under tolcapone therapy. (PubMed, Front Med (Lausanne)) - "This report highlights progressive CNS involvement in Ala45Thr-associated ATTR despite treatment with a CNS-penetrant TTR stabilizer. These findings suggest that disease progression may continue despite TTR stabilization in some patients and underscore the need for early intervention, systematic CNS monitoring, and further development of CNS-targeted therapies."

Journal • Amyloidosis • Ataxia • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Hematological Disorders • Movement Disorders • Pain

Gait Analysis in Neurological Disease (clinicaltrials.gov) - P=N/A | N=120 | Active, not recruiting | Sponsor: Beth Israel Deaconess Medical Center | Recruiting ➔ Active, not recruiting | Trial completion date: Jun 2026 ➔ Jul 2027 | Trial primary completion date: Jun 2026 ➔ Jul 2027

Enrollment closed • Trial completion date • Trial primary completion date • Ataxia • CNS Disorders • Genetic Disorders • Huntington's Disease • Movement Disorders • Multiple System Atrophy • Parkinson's Disease • Progressive Supranuclear Palsy

Dopamine-Enhancing Therapies and Risk of Neovascular AMD Conversion: A Target Trial Emulation. (PubMed, Am J Ophthalmol) - "In this cohort study, levodopa ± carbidopa use was associated with lower 3-year risk of conversion to nAMD in two independent matched comparisons, whereas DRD2 agonists were not associated with significant differences in risk. These findings suggest dopaminergic signaling may influence AMD progression and warrant further prospective investigation."

Journal • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • DRD2

Tolcapone-loaded nanostructured lipid carriers for improved oral delivery. (PubMed, Int J Pharm) - "elegans) demonstrated survival percentages > 88% after acute exposure to the nanoformulations in concentrations up to 100 µM. Together, the results obtained so far demonstrate that tolcapone-loaded NLCs have the potential to be a valid therapeutic option for the treatment of PD in the future."

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

COMT Inhibition Among Individuals With Comorbid AUD/ADHD (clinicaltrials.gov) - P2 | N=23 | Completed | Sponsor: University of Colorado, Denver | Recruiting ➔ Completed | N=62 ➔ 23 | Trial completion date: Mar 2025 ➔ Mar 2026 | Trial primary completion date: Mar 2025 ➔ Mar 2026

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Addiction (Opioid and Alcohol) • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

Microbiome Derived Metabolism and Pharmacokinetics (clinicaltrials.gov) - P1 | N=17 | Completed | Sponsor: Rutgers, The State University of New Jersey | Recruiting ➔ Completed | Trial completion date: Dec 2025 ➔ Sep 2025

Trial completion • Trial completion date • Infectious Disease

rs4680-tolcapona: EVALUATION OF THE EFFICACY OF TOLCAPONE AS A GENOTYPE-BASED TARGETED COGNITIVE ENHANCER IN SCHIZOPHRENIA, BASED ON THE POLYMORPHISM RS4680 (clinicaltrialsregister.eu) - P1/2 | N=20 | Completed | Sponsor: Clinica Universidad De Navarra | Not yet recruiting ➔ Completed

Trial completion • CNS Disorders • Psychiatry • Schizophrenia

Venlafaxine upregulates cortical catechol-O-methyltransferase expression and activity in rats and mice. (PubMed, Drug Metab Dispos) - "Phosphatidylinositol 3-kinase inhibitor LY294002, mammalian target of rapamycin inhibitor rapamycin, silencing P70S6K, or silencing 4EBP1 remarkably attenuated venlafaxine-induced upregulation of COMT...Furthermore, COMT inhibitor tolcapone reversed venlafaxine-induced decreases in SAM levels, H3K4me3 and H3K27me3 expression, and locomotor and exploration activities...SIGNIFICANCE STATEMENT: This study revealed that venlafaxine upregulated cortical catechol-O-methyltransferase expression and activity via activating phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin pathway. The induction of catechol-O-methyltransferase led to depletion of cortical S-adenosylmethionine, which may partly contribute to the decreases in locomotor and exploration activities and downregulations of H3K4me3 and H3K27me3 expression in cortex of rats and mice."

Journal • Preclinical • COMT • EIF4EBP1

EFFECTS OF MAO-B AND COMT INHIBITORS ON SLEEP DISTURBANCES IN PARKINSON'S DISEASE: A NETWORK META-ANALYSIS (ADPD 2026) - "Inclusion criteria involved (1) patients with PD, (2) intervention/comparator consisting of MAO-B inhibitors (safinamide, rasagiline, or selegiline) and COMT inhibitors (opicapone, entacapone, or tolcapone), and (3) outcomes of improvement in parameters for subjective and objective sleep in randomized controlled trials and cohort studies. A total of 529 articles were identified during the initial search, and we ultimately conducted an NMA focusing on the final seven studies. Evidence has shown that safinamide is effective in improving objective sleep parameters in patients with PD. However, given the paucity of evidence and controlled, long-term studies, the effects of MAO-B and COMT inhibitors on sleep disturbances remain unclear. More high-quality studies will be needed and should enable clinicians to provide personalized medicine based on sleep profiles."

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

EFFICACY OF MAO-B AND COMT INHIBITORS ON QUALITY OF LIFE IN PATIENTS WITH PARKINSON'S DISEASE: A BAYESIAN NETWORK META-ANALYSIS (ADPD 2026) - "Randomized controlled trials evaluating QoL using PDQ-39 or PDQ-8 in patients treated with MAO-B inhibitors (rasagiline, selegiline, safinamide) or COMT inhibitors (entacapone, opicapone, tolcapone) were included. This network meta-analysis provides evidence that MAO-B inhibitors, particularly rasagiline and safinamide, may offer broader QoL benefits in patients with PD, especially in NMS such as emotional well-being. These findings support a more symptom-oriented and individualized treatment approach should be provided to patients with PD. Further well-designed head-to-head studies using standardized QoL measures and extended follow-up are needed to confirm these findings and guide clinical practice."

HEOR • Retrospective data • CNS Disorders • Movement Disorders • Parkinson's Disease • COMT

A Clinical Trial of Tolcapone in Obsessive Compulsive Disorder (clinicaltrials.gov) - P2 | N=49 | Active, not recruiting | Sponsor: University of Chicago | Recruiting ➔ Active, not recruiting | N=85 ➔ 49

Enrollment change • Enrollment closed • Mood Disorders • Obsessive-Compulsive Disorder • Psychiatry

Tolcapone Interferes With Key Pathological Features in Alzheimer's Disease. (PubMed, Bioinorg Chem Appl) - "Furthermore, in vitro assays confirm the capacity of tolcapone to act as a radical scavenger and to compete with amyloid-β for the binding of copper ions. Altogether, our findings suggest that tolcapone exerts a multifaceted protective effect, potentially inhibiting toxic metal-free and metal aggregation pathways by preventing metal coordination to amyloid-β or disrupting preformed amyloid-β-metal complexes, thus offering new perspectives to explore and develop its analogs for the treatment of neurodegenerative disorders."

Journal • Age-related Macular Degeneration • Alzheimer's Disease • CNS Disorders • Glaucoma • Macular Degeneration • Movement Disorders • Ophthalmology • Parkinson's Disease • Retinal Disorders

Consensus Molecules Associated with Parkinson's Disease. (PubMed, Neurol Int) - "Drugs include L-dopa (49%), carbidopa (63%), benserazide (50%), entacapone (74%), tolcapone (56%), rasagiline (76%), selegiline (46%), pargyline (4%), ropinirole (61%), pramipexole (56%), lisuride (27%), cabergoline (16%), bromocriptine (12%), and zonisamide (9%). Adjunctive therapies include droxidopa (33%), trihexyphenidyl (28%), biperiden (17%), amantadine (24%), memantine (7%), rivastigmine (13%), donepezil (6%), galantamine (4%), domperidone (6%), clonazepam (4%), tetrabenazine (16%), mazindol (13%), quetiapine (6%), and clozapine (4%). Contraindicated drugs include haloperidol (4%), sulpiride (3%), and methyldopa (6%)...Chemical inducers of PD include 6-hydroxydopamine (40%), N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 78%), tetrahydropyridine (77%), probenecid (4%), quinolinic acid (4%), 1,2,3,4-tetrahydroisoquinoline (TIQ, 16%), salsolinol (32%), rotenone (25%), and β-Methylamino-L-alanine (BMAA, 29%). Notably, our study highlights conditional essential..."

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

Efficacy of MAO-B and COMT inhibitors on quality of life in patients with Parkinson's disease: a Bayesian network meta-analysis. (PubMed, Front Neurol) - "Randomized controlled trials evaluating QoL using PDQ-39 or PDQ-8 in patients treated with MAO-B inhibitors (rasagiline, selegiline, safinamide) or COMT inhibitors (entacapone, opicapone, tolcapone) were included. Further well-designed head-to-head studies using standardized QoL measures and extended follow-up are needed to confirm these findings and guide clinical practice. Registered in PROSPERO (CRD420251013028): https://www.crd.york.ac.uk/PROSPERO/view/CRD420251013028."

HEOR • Journal • Retrospective data • Review • CNS Disorders • Movement Disorders • Parkinson's Disease • COMT

Synthesis, Structural Characterization, and In Silico Evaluation of the Salicylidene Schiff Base 4‑{(E)‑[(2,3-Dihydroxyphenyl)methylidene]amino}-2-hydroxybenzoic Acid as a Promising Scaffold for Human Transthyretin Inhibitor. (PubMed, ACS Omega) - "Single-crystal X-ray diffraction analysis showed that the compound crystallizes in the triclinic P1̅ space group with two molecules in the asymmetric unit, both adopting a zwitterionic keto form. In silico studies predict high gastrointestinal absorption, low toxicity, and potential activity as a transthyretin (TTR) inhibitor, with binding affinity comparable to that of the drug Tolcapone, suggesting that the synthesized compound may be a promising scaffold for a TTR stabilizer."

Journal

A Clinical Trial of Tolcapone in Obsessive Compulsive Disorder (clinicaltrials.gov) - P2 | N=85 | Recruiting | Sponsor: University of Chicago | Trial completion date: Jan 2026 ➔ Jun 2026 | Trial primary completion date: Dec 2025 ➔ Jun 2026

Trial completion date • Trial primary completion date • Mood Disorders • Obsessive-Compulsive Disorder • Psychiatry

The Parkinson's Disease Drug Tolcapone and Analogues are Potent Glycomimetic Lectin Inhibitors of Pseudomonas aeruginosa LecA. (PubMed, Angew Chem Int Ed Engl) - "Motivated by the pressing need for new anti-infective therapies caused by antimicrobial resistance, inhibitors of LecA are under investigation. This work paves the way for a new avenue of research towards innovative anti-infective drugs. In a more general perspective, such small molecules also hold potential to challenge the hegemony of antibodies for lectin inhibition in clinical use."

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

Safety of COMT-inhibitors in parkinson's disease: a phase-IV comparative study on adverse events of Tolcapone, Entacapone and Opicapone. (PubMed, J Neural Transm (Vienna)) - "Entacapone appears to be the safest long-term COMT-inhibitor, with the lowest risk of both serious and non-serious AEs. A long-term, prospective clinical trial is warranted to overcome retrospective limitations and confirm these findings."

Adverse events • Journal • P4 data • CNS Disorders • Movement Disorders • Parkinson's Disease • COMT

Remediation of Impaired Self-Regulation in Patients With Mild TBI (clinicaltrials.gov) - P1 | N=55 | Completed | Sponsor: VA Office of Research and Development | Phase classification: P=N/A ➔ P1

Phase classification • CNS Disorders • Vascular Neurology

Prioritizing repurposable drugs for Alzheimer's disease using network-based analysis with concurrent assessment of Long QT syndrome risk. (PubMed, Biotechnol Rep (Amst)) - "This strategy identified promising compounds including acamprosate, tolcapone, sitagliptin, and diazoxide, with potential to mitigate disease pathology. Gene set enrichment analysis was used to computationally assess the compounds' ability to reverse disease-related gene expression signatures."

Journal • Alzheimer's Disease • Cardiovascular • CNS Disorders

Digital absorption spectral database of hydroxybenzophenones (ACS-Fall 2025) - "Benzophenones are widely used as photosensitizers, synthetic precursors to pharmaceuticals (e.g., tolcapone, fenofibrate) and polymers (polyether-ketones). The absorption spectral data can be viewed and downloaded at no cost at the website http://www.photochemcad.com. The availability of the digital spectral data enables calculations of the sun protecting factor (SPF), which should facilitate evaluation of hydroxybenzophenones as ultraviolet protecting agents."

Differentiating the solution structures and stability of transthyretin tetramer complexed with tolcapone and tafamidis using SEC-SWAXS and NMR. (PubMed, J Appl Crystallogr) - "Additionally, under a reduced TTR-drug mixing ratio of 1:1, which targets only one T4 site, tafamidis more effectively stabilizes the TTR tetrameric conformation at 8 M urea, a difference attributed to its higher affinity for the first T4 site. These results illustrate an effective strategy for investigating protein-drug interactions by examining the solution conformations of protein-drug complexes under physiological conditions, providing structural hints to the design of therapeutic agents targeting TTR."

Journal

The Seminal Role of the Proinflammatory Cytokine IL-1β and Its Signaling Cascade in Glioblastoma Pathogenesis and the Therapeutic Effect of Interleukin-1β Receptor Antagonist (IL-1RA) and Tolcapone. (PubMed, Int J Mol Sci) - "In contrast, IL-1RA and Tolcapone inhibited this proliferation and the expression of these mRNAs and proteins, inhibiting autophagy by downregulating these autophagy proteins and inducing apoptosis by upregulating the expression of pro-apoptotic proteins like caspase-8 and caspase-3. IL-1β and its receptor can be targeted for successful anticancer therapy, as shown here with the use of IL-1RA and/or Tolcapone."

Journal • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • CASP3 • CASP8 • CTSB • GFAP • IL1B • IL1R1 • IL6 • MYD88 • TNFA

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