tolcapone / Generic mfg. - LARVOL DELTA

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

Exploring Potential Causal Links: How Parkinson's Disease Brain Damage Impacts Liver Health-A Mendelian Randomization and Transcriptomic Study. (PubMed, J Inflamm Res) - "Interestingly, the anti-PD drug, tolcapone, has notable therapeutic effects but also negatively affects specific genes, contributing to liver damage in patients with PD...Furthermore, the impact of PD treatment drugs on liver function was also evaluated. These findings provide important insights for the development of future PD treatment strategies, and further clinical research is needed to validate and optimize clinical interventions to maximize treatment efficacy and minimize side effects in patients with PD."

Journal • CNS Disorders • Hepatology • Inflammation • Movement Disorders • Parkinson's Disease • Vascular Neurology

Effects of COMT suppression in a randomized trial on the neural correlates of inhibitory processing among people with Alcohol Use Disorder. (PubMed, Biol Psychiatry Cogn Neurosci Neuroimaging) - "Tolcapone increased activation of cortical areas implicated in inhibitory control. The associations between increased iFG activation and connectivity, improved inhibitory control, and reduced drinking suggest that pharmacological interventions that increase cortical dopamine may rescue dysregulated inhibitory control among people with AUD."

Journal • Addiction (Opioid and Alcohol) • COMT

Gait Analysis in Neurological Disease (clinicaltrials.gov) - P=N/A | N=120 | Recruiting | Sponsor: Beth Israel Deaconess Medical Center | Trial completion date: Jun 2025 ➔ Jun 2026 | Trial primary completion date: Jun 2025 ➔ Jun 2026

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

Type A asparagine synthetase in the zoonotic Cryptosporidium parvum (CpAsnA): Biochemical features and potential as a novel therapeutic target. (PubMed, Int J Parasitol Drugs Drug Resist) - "Four of the 31 TSA hits exhibited lower micromolar activity against CpAsnA enzyme activity, including XD14, SB225002, histone acetyltransferase inhibitor II (HATi-II) and tolcapone. Among the four CpAsnA inhibitors, three displayed lower micromolar in vitro efficacy against the growth of C. parvum in vitro with satisfactory selectivity indices as primary antiparasitic hits. Our data suggest that CpAsnA merits further investigation as a potential drug target in the parasite."

Journal • ASNS

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

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

Clinical pharmacokinetics of levodopa and relevant add-on therapies for Parkinson's disease. (PubMed, Expert Opin Drug Metab Toxicol) - "Opicapone induced higher levodopa plasma levels compared with the ones following application of levodopa/carbidopa alone or combined with entacapone or tolcapone. Co-administration of opicapone with its once daily intake regimen may support the efficacy of subcutaneous and intrajejunal levodopa infusions."

Journal • PK/PD data • Review • CNS Disorders • Movement Disorders • Parkinson's Disease • COMT

Microbiome Derived Metabolism and Pharmacokinetics (clinicaltrials.gov) - P1 | N=14 | Recruiting | Sponsor: Rutgers, The State University of New Jersey | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Jun 2024 ➔ Dec 2025

Trial completion date • Trial primary completion date • Infectious Disease

Sleep deprivation-induced memory impairment: exploring potential interventions. (PubMed, Front Psychiatry) - "The review discusses various interventions, ranging from pharmaceutical compounds like donepezil, memantine, and tolcapone, to innovative physical therapy techniques such as transcranial magnetic stimulation (TMS), deep brain stimulation (DBS), and transcranial direct current stimulation (tDCS). Additionally, the emerging role of the gut-brain axis in sleep deprivation-induced memory impairment is examined, shedding light on the complex interplay between gut microbiota and cognitive functions. This comprehensive review explores the multifaceted relationship between sleep deprivation and memory impairment, delving into the neurobiological mechanisms underlying these processes and examining potential interventions."

Journal • Alzheimer's Disease • CNS Disorders

Discovery of a Potent, Selective, and Blood-Brain Barrier Permeable Non-nitrocatechol Inhibitor of Catechol-O-methyltransferase. (PubMed, J Med Chem) - "A new library of non-nitrocatechol compounds (HetCAMs) was developed and their efficacy was compared to tolcapone, a standard COMT inhibitor for PD...Additionally, compound 9 is predicted to cross the blood-brain barrier (BBB) by passive diffusion and chelate divalent metals like Fe(II) and Cu(II). The results demonstrate the potential of this rational drug design strategy for developing new CNS-active drug candidates, offering symptom relief via COMT inhibition that can provide a long-term, disease-modifying outcome (chelation of divalent metals) in PD."

Journal • COMT

Opicapone real-world experience in early motor fluctuations: 3-months analysis of the REONPARK study. (MDS Congress 2024) - "Available iCOMT include opicapone, entacapone and tolcapone. Opicapone demonstrated effective control of motor symptoms and good tolerability in PD patients with EMF in routine clinical practice after 3 months."

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

Opicapone Reduces Homocysteine Levels in Patients with Parkinson's Disease Treated with Levodopa Gel Infusion (MDS Congress 2024) - "We have previously proved that add-on treatment with COMT inhibitor tolcapone reduced LCIG/CLES daily dose and decreased HCY levels [1]. Opicapone might have the potential to reduce HCY plasmatic levels in patients with advanced PD treated by LCIG/CLES, probably by decreased peripheral conversion of levodopa to 3-O-methyldopa and, thus, also possibility to reduce the daily dose of LCIG/CLES. The change in homocysteine levels (in μmol/l)"

Clinical • CNS Disorders • Parkinson's Disease • COMT

Drug Discovery and Screening Tool Development for Tauopathies by Focusing on Pathogenic Tau Repeat 3 Oligomers. (PubMed, Angew Chem Int Ed Engl) - "Through screening, tolcapone was found to possess therapeutic efficacy against pathological tau aggregates in PS19 transgenic mice. This screening platform provides a valuable avenue for identifying compounds that selectively interact with peptides implicated in the progression of tauopathies."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders

Modeling Lewy body disease with SNCA triplication iPSC-derived cortical organoids and identifying therapeutic drugs. (PubMed, Sci Adv) - "Furthermore, we screened 1280 Food and Drug Administration-approved drugs and identified four candidates (entacapone, tolcapone, phenazopyridine hydrochloride, and zalcitabine) that inhibited α-SYN seeding activity in real-time quaking-induced conversion assays with human brains, reduced α-SYN aggregation, and alleviated mitochondrial dysfunction in SNCA triplication organoids and excitatory neurons. Our findings establish human cortical LBD models and suggest potential therapeutic drugs targeting α-SYN aggregation for LBD."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Dementia • Lewy Body Disease • Metabolic Disorders • SNCA

The Catechol O-Methyltransferase Inhibitor Entacapone in the Treatment of Parkinson's Disease: Personal Reflections on a First-in-Class Drug Development Programme 40 Years On. (PubMed, Neurol Ther) - "Subsequently, entacapone has been amalgamated into a triple-combination preparation (Stalevo®) with levodopa and carbidopa to create a flexible and convenient drug therapy for patients with PD who have end-of-dose motor fluctuations not stabilised on levodopa/dopa-decarboxylase inhibitor treatment. This review offers a historical perspective on a successful programme of drug development by researchers who played central roles in the progress from exploratory hypothesis to registered pharmaceutical product."

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

Validating Well-Functioning Hepatic Organoids for Toxicity Evaluation. (PubMed, Toxics) - "Subsequently, utilizing these functionally validated hepatic organoids, we conducted toxicity evaluations with three hepatotoxic substances (ketoconazole, troglitazone, and tolcapone), which are well known for causing drug-induced liver injury, and three non-hepatotoxic substances (sucrose, ascorbic acid, and biotin). The organoids effectively distinguished between the toxicity levels of substances with and without hepatic toxicity. We demonstrated the potential of hepatic organoids with validated functionalities and genetic characteristics as promising models for toxicity evaluation by analyzing toxicological changes occurring in hepatoxic drug-treated organoids."

Journal • Hepatology • Liver Failure

Pivotal Roles of Mitochondria in Linking Dopamine Catabolism to Axonal Myelination: Implication for the Pathogenesis and Treatment of Schizophrenia (WFSBP 2024) - " Adolescent C57BL/6 mice administered tolcapone (TOL) for two weeks exhibited elevated DA levels in the prefrontal cortex (PFC), mitochondrial dysfunction in brain cells, and dose-dependent hypomyelination in the PFC, hippocampus, and caudate putamen (CPu), alongside schizophrenia-related behaviors... These findings underscore the critical role of mitochondria in linking DA catabolism to axonal myelination in the brain, offering new insights into schizophrenia pathogenesis and therapeutic strategies."

CNS Disorders • Psychiatry • Schizophrenia • COMT