Comtan (entacapone) / Novartis, Orion Corp, Alvogen - LARVOL DELTA

EM-PD: Efficacy and Safety of Entacapone Combined With Madopar in the Treatment of Early Parkinson's Disease (PD): A Prospective, Multicenter, Non-Randomized Controlled Study (clinicaltrials.gov) - P4 | N=216 | Not yet recruiting | Sponsor: Yousheng Xiao

New P4 trial • CNS Disorders • Movement Disorders • Parkinson's Disease

Target-Controlled Sedation with Propofol Infusion for PEG-J Placement in Advanced Parkinson's Disease: A Prospective Observational Study on Safety and Feasibility. (PubMed, Life (Basel)) - "This study highlights the feasibility and clinical applicability of a TCI propofol protocol for PEG-J placement in patients with advanced PD (stages 4 and 5). While no deaths were recorded within the 30-day follow-up, the sample size is insufficient to draw definitive conclusions regarding long-term safety."

Journal • Observational data • Anesthesia • CNS Disorders • Movement Disorders • Parkinson's Disease

Discovery of the 2,3-Dihydrobenzopyrane-4-one as a Potent FTO Inhibitor against Obesity-Related Metabolic Diseases. (PubMed, J Med Chem) - "However, the existing FTO inhibitor entacapone has been limited in clinical application due to its low potency and short plasma elimination half-life...Surprisingly, eriodictyol showed good pharmacokinetic properties and no obvious toxicity. These results could provide the reference for design of new FTO inhibitors against obesity-related metabolic diseases."

Journal • Genetic Disorders • Metabolic Disorders • Obesity

Combinations of compound cold medicines should be used with caution: a case series. (PubMed, Front Med (Lausanne)) - "In Case 1, a 67-year-old woman with no history of coronary artery disease or angina developed angina after concurrently taking diltiazem and compound methoxyphenamine. In Case 2, a 65-year-old man who was taking propylthiouracil for a year without any adverse reactions experienced mental status abnormalities and acute liver failure after taking "CONTAC NT." In Case 3, a 63-year-old man, who was taking levodopa, entacapone, and selegiline for a long time, without any apparent adverse reactions, developed serotonin syndrome after adding CONTAC NT. These issues were resolved after the discontinuation of medication. Patients should consult a pharmacist or physician before using compound cold medicines to avoid the risk of adverse reactions caused by drug-drug interactions."

Journal • Cardiovascular • Coronary Artery Disease • Hepatology • Infectious Disease • Liver Failure • Respiratory Diseases

Levodopa-Entacapone-Carbidopa Intrajejunal Infusion in Advanced Parkinson's Disease - Interim Analysis of the ELEGANCE Study. (PubMed, Mov Disord Clin Pract) - P | "Routine use of LECIG for up to 12 months provided sustained control of motor symptoms, and was well tolerated with a positive impact on QoL and high patient satisfaction."

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

Device-aided therapies (DATs) in Parkinson's disease (PD). The DATs-PD GETM Spanish Registry Protocol Study. (PubMed, PLoS One) - "The present study will help improve the care of PD patients treated with a DAT."

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

Deregulation of FTO isoforms correlates with the progression of metabolic dysfunction associated steatotic liver disease and its amelioration with Entacapone (APASL 2025) - "The present study suggests that FTO expression is deregulated during the progression of NAFLD to NASH. Isoform FTO-12 is selectively overexpressed in cirrhosis, whereas levels of isoforms 1, 3, and 5 are elevated in NAFLD and NASH. Treatment with entacapone normalized the expression of FTO isoforms in the NAFLD model of primary human hepatocytes suggesting its therapeutic potential in mitigating the progression of liver disease."

Diabetes • Fibrosis • Genetic Disorders • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Type 2 Diabetes Mellitus • FTO • LEP

Relationship between changes in 3-OMD blood concentration and oral dosage of levodopa and entacapone (JSNE 2025) - No abstract available

CNS Disorders • Gene Therapies • Movement Disorders • Parkinson's Disease

The "Wearing Off" Phenomenon for Rasagiline, Entacapone, Carbidopa, and Levodopa in the Setting of Parkinson's Disease. (PubMed, HCA Healthc J Med) - "Initially, the patient was prescribed carbidopa/levodopa, rasagiline, and carbidopa/levodopa/entacapone. To effectively address the intricate relationship between motor symptoms and psychiatric manifestations, it is imperative to implement a multidisciplinary team approach in future management. This approach would involve closely monitoring and adapting treatment strategies."

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

Update on Treatments for Parkinson's Disease Motor Fluctuations - An International Parkinson and Movement Disorder Society Evidence-Based Medicine Review. (PubMed, Mov Disord) - "There are several treatment options that can improve motor fluctuations in PD. These recommendations will assist physicians and patients in determining which intervention to use."

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

Quantitative prediction of drug disposition for uridine diphosphate-glucuronosyltransferase substrates using humanized mice. (PubMed, Drug Metab Dispos) - "To estimate human hepatic intrinsic clearance (CLh,int) in vitro, UGT substrates (acetaminophen, entacapone, ketoprofen, lorazepam, oxazepam, posaconazole, and zidovudine) were incubated with cryopreserved human hepatocytes...For predicting UGT-mediated drug-drug interactions, 2 UGT substrates were administered intravenously to hu-PXB mice with or without probenecid (a UGT inhibitor)...SIGNIFICANCE STATEMENT: Human liver chimeric mice can accurately predict the clearance of uridine diphosphate-glucuronosyltransferase (UGT) substrate drugs and are likely to predict the magnitude of UGT-mediated drug-drug interactions. Findings from in vivo studies in humanized mice enable the selection of better candidates in drug discovery and allow for the more precise physiologically based pharmacokinetic modeling of UGT substrate drugs in clinical practice."

Journal • Preclinical • Genetic Disorders • Immunology • Primary Immunodeficiency • Transplantation

[18F]F-DOPA Imaging in Patients with Autonomic Failure (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: Daniel Claassen | Trial completion date: Feb 2025 ➔ Feb 2026 | Trial primary completion date: Feb 2025 ➔ Feb 2026

Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders • Dementia • Lewy Body Disease • Movement Disorders • Multiple System Atrophy • Parkinson's Disease

Two years' experience with levodopa-entacapone-carbidopa intestinal gel treatment in advanced Parkinson's disease (PubMed, Orv Hetil) - No abstract available

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

Roles of N6-Methyladenosine in LncRNA Changes and Oxidative Damage in Cadmium-Induced Pancreatic β-cells. (PubMed, Toxicology) - "In this study, m6A agonist entacapone and inhibitor 3-deazadenosine were used to identify the effects of m6A on cadmium-induced oxidative damage as well as LncRNA changes...In conclusion, our data revealed critical roles of m6A modification in cadmium-induced LncRNAs and oxidative damage. Our findings point to a new direction for future studies on the molecular mechanisms of pancreatic β-cell damage induced by cadmium."

Journal

Challenges of equitable access to device-aided therapies for advanced Parkinson's Disease in Poland - expert consensus and treatment recommendations. (PubMed, Neurol Neurochir Pol) - "Consensus expert opinion is that APD patients in Poland would benefit from additional reimbursement access to these treatment options to improve APD patient care."

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

In Silico Analysis of Triamterene as a Potential Dual Inhibitor of VEGFR-2 and c-Met Receptors. (PubMed, J Xenobiot) - "The results revealed that entacapone and telmisartan are potent and selective inhibitors for c-Met and VEGFR-2, respectively. Our study provides a foundational framework for the development of novel anticancer compounds able to target multiple pathways in cancer. Further preclinical and clinical investigations are needed to validate the efficacy of these compounds in clinical settings and to test their ability to overcome resistance and improve patient outcome."

Journal • Oncology • KDR • MET

N6-methyladenosine mediated-NRF2 signaling pathway attenuates cadmium cytotoxicity by inhibiting oxidative damage in bronchial epithelial cells. (PubMed, Toxicol Lett) - "It is noteworthy that pretreatment with the m6A agonist entacapone (ENT) markedly attenuated the detrimental effects of cadmium, including cell death, oxidative damage, and the activation of the nuclear factor erythroid 2-related factor 2（NRF2）signalling pathway...In conclusion, our data together suggest that m6A modification play critical roles in cadmium-induced bronchial epithelial cell damage, during which NRF2 signaling pathway may act as an important bridge for m6A modification to regulate cellular damage. This study offer a promising avenue for further investigation into the mechanisms underlying cadmium-induced bronchial epithelial cell damage from the perspective of RNA epigenetics."

Journal • ALKBH5 • FTO • YTHDC2

Entacapone alleviates muscle atrophy by modulating oxidative stress, proteolysis, and lipid aggregation in multiple mice models. (PubMed, Front Physiol) - "C2C12 cells were treated with dexamethasone (Dex) to simulate muscle atrophy. Our findings suggest that entacapone is a promising therapeutic candidate for muscle atrophy, functioning through the reduction of oxidative stress, proteolysis, and lipid aggregation. Future research should explore the underlying mechanisms and potential clinical applications of entacapone in muscle-wasting conditions."

Journal • Preclinical • Dyslipidemia • Muscular Atrophy • Targeted Protein Degradation • FBXO32 • SOD1 • SOD2

Levodopa-entacapone-carbidopa intestinal gel: Data from the Swedish national registry for Parkinson's disease. (PubMed, Eur J Neurol) - "Data from ParkReg covering 150 patients over 3 years show LECIG to be an effective and safe device-aided therapy for advanced PD. However, the long-term efficacy and tolerability of LECIG need to be further investigated."

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

Biomimetic Approach for Optimal Designing of the Shape and Controlled Release of Therapeutics from Tricompartmental Microcarriers for Managing Parkinson's Disease. (PubMed, ACS Appl Bio Mater) - "While jetting, Levodopa (LD), CD (Carbidopa), and ENT (Entacapone) (3 PD drugs) were directly encapsulated in the three individual compartments of the TCM used for oral administration. Moreover, Poptimized exhibits ∼100% encapsulation efficiency of all three PD drugs, with the cumulative release of ∼100% LD, ∼97% CD, and ∼65% ENT within 5 h of the in vitro study. In addition, in vivo studies such as pharmacokinetics (using healthy rats) and pharmacodynamics [using the MPTP (methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-injected PD-induced mice model] showed that the TCM can effectively control the release of LD (primary drug) for a prolonged period, thereby promising sustained drug delivery and improved therapeutics outcomes."

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

The Parkinson's disease drug entacapone disrupts gut microbiome homoeostasis via iron sequestration. (PubMed, Nat Microbiol) - "Further, entacapone-induced iron starvation selected for iron-scavenging gut microbiome members encoding antimicrobial resistance and virulence genes. These findings reveal the impact of two under-investigated drugs on whole microbiomes and identify metal sequestration as a mechanism of drug-induced microbiome disturbance."

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

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

Effectiveness and safety of levodopa-entacapone-carbidopa infusion in Parkinson disease: A real-world data study. (PubMed, Eur J Neurol) - "LECIG was safe and effective in advanced PD patients."

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

A 4-Year Follow-Up of Levodopa-Entacapone-Carbidopa Intestinal Gel Treatment in Parkinson's Disease. (PubMed, Mov Disord Clin Pract) - "LECIG infusion is a viable treatment option for PD patients with motor fluctuations, for up to 4 years in our cohort."

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

Prescription trends in Japanese advanced Parkinson's disease patients with non-motor symptoms: J-FIRST. (PubMed, PLoS One) - "There were significant changes in the prescriptions and dosing of selected anti-PD drugs, especially newer drugs. Anti-PD drug and NSAID prescriptions also varied by changes in NMS status and geographic region."

Journal • Metastases • Observational data • CNS Disorders • Movement Disorders • Parkinson's Disease