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https://www.readbyqxmd.com/read/29695590/effectiveness-of-opicapone-and-switching-from-entacapone-in-fluctuating-parkinson-disease
#1
Joaquim J Ferreira, Andrew J Lees, Werner Poewe, Olivier Rascol, José-Francisco Rocha, Birgit Keller, Patricio Soares-da-Silva
OBJECTIVE: To evaluate the effectiveness of opicapone as add-on to levodopa and the effects of switching from entacapone over 1 year of treatment in patients with fluctuating Parkinson disease. METHODS: After completion of a placebo- and entacapone-controlled double-blind study of opicapone (5, 25, or 50 mg), 495 patients continued to a 1-year extension phase in which patients were treated with opicapone. Patients began with once-daily opicapone 25 mg for 1 week, followed by individually tailored levodopa and/or opicapone dose adjustments...
April 25, 2018: Neurology
https://www.readbyqxmd.com/read/29670409/safinamide-an-add-on-treatment-for-managing-parkinson-s-disease
#2
REVIEW
Thomas Müller
Heterogeneous expression of neurotransmitter deficits results from onset and progression of Parkinson's disease. Intervals, characterized by reappearance of motor and associated certain nonmotor symptoms, determine the end of good tolerability and efficacy of oral levodopa therapy. These "OFF" states result from levodopa pharmacokinetics and disease progression-related deterioration of the central buffering capacity for fluctuations of dopamine levels. This review discusses safinamide as an add-on therapeutic agent in orally levodopa-treated patients with "OFF" phenomena...
2018: Clinical Pharmacology: Advances and Applications
https://www.readbyqxmd.com/read/29614697/are-there-benefits-in-adding-catechol-o-methyltransferase-inhibitors-in-the-pharmacotherapy-of-parkinson-s-disease-patients-a-systematic-review
#3
Irene Katsaiti, John Nixon
BACKGROUND: A qualified consensus suggests that a combination of levodopa with a peripherally acting dopa decarboxylase inhibitor continues to present the gold standard treatment of Parkinson's disease (PD). However, as the disease progresses the therapeutic window of levodopa becomes narrowed. Pharmacological strategies for motor fluctuations are focused on providing less pulsatile and more continuous dopaminergic stimulation. Peripheral catechol-O-methyltransferase (COMT) inhibition improves the bioavailability of levodopa and results in a prolonged response...
March 26, 2018: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/29570866/international-parkinson-and-movement-disorder-society-evidence-based-medicine-review-update-on-treatments-for-the-motor-symptoms-of-parkinson-s-disease
#4
REVIEW
Susan H Fox, Regina Katzenschlager, Shen-Yang Lim, Brandon Barton, Rob M A de Bie, Klaus Seppi, Miguel Coelho, Cristina Sampaio
OBJECTIVE: The objective of this review was to update evidence-based medicine recommendations for treating motor symptoms of Parkinson's disease (PD). BACKGROUND: The Movement Disorder Society Evidence-Based Medicine Committee recommendations for treatments of PD were first published in 2002 and updated in 2011, and we continued the review to December 31, 2016. METHODS: Level I studies of interventions for motor symptoms were reviewed. Criteria for inclusion and quality scoring were as previously reported...
March 23, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/29570862/medical-and-surgical-management-of-advanced-parkinson-s-disease
#5
REVIEW
Angelo Antonini, Elena Moro, Clecio Godeiro, Heinz Reichmann
Advanced Parkinson's disease is characterized by the presence of motor fluctuations, various degree of dyskinesia, and disability with functional impact on activities of daily living and independence. Therapeutic management aims to extend levodopa benefit while minimizing motor complications and includes, in selected cases, the implementation of drug infusion and surgical techniques. In milder forms of motor complications, these can often be controlled with manipulation of levodopa dose and the introduction of supplemental therapies such as catechol-O-methyl transferase inhibitors, monoamine oxidase B inhibitors, and dopamine agonists including apomorphine...
March 23, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/29415596/the-launch-of-opicapone-for-parkinson-s-disease-negatives-versus-positives
#6
REVIEW
Ana Castro Caldas, Tiago Teodoro, Joaquim J Ferreira
Opicapone is a novel, third generation COMT inhibitor approved for the treatment of Parkinson's disease. Safety and tolerability data is critical to determine the benefit-harm balance and anticipate therapeutic adherence. Areas covered: This review evaluates the tolerability and safety profile of opicapone. These data were extracted from all published clinical trials, including preclinical, phase I, phase II and phase III studies as well as postmarketing data. Opicapone was safe and well tolerated, with frequencies of treatment-emergent adverse events similar to placebo...
March 2018: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/29345156/pharmacokinetic-drug-evaluation-of-opicapone-for-the-treatment-of-parkinson-s-disease
#7
Marina Svetel, Aleksandra Tomić, Nikola Kresojević, Vladimir Kostić
Opicapone (OPC) is a novel, potent, reversible, and purely peripheral third-generation COMT inhibitor, which provides an enhancement in levodopa (L-Dopa) availability. It represents adjunctive therapy for L-Dopa treated patients with PD and motor fluctuations. Areas covered: The purpose of this study was to evaluate pharmacokinetic of OPC for the treatment of PD. Expert commentary: Oral OPC exhibits linear, dose-dependent absorption. However, following concomitant ingestion of a high-fat, high-calorie meal, the maximum plasma concentration will be decreased...
January 24, 2018: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/29281938/pharmacophore-based-virtual-screening-of-catechol-o-methyltransferase-comt-inhibitors-to-combat-alzheimer-s-disease
#8
Chirag N Patel, John J Georrge, Krunal M Modi, Moksha B Narechania, Daxesh P Patel, Frank J Gonzalez, Himanshu A Pandya
Alzheimer's disease (AD) is one of the most significant neurodegenerative disorders and its symptoms mostly appear in aged people. Catechol-o-methyltransferase (COMT) is one of the known target enzymes responsible for AD. With the use of 23 known inhibitors of COMT, a query has been generated and validated by screening against the database of 1500 decoys to obtain the GH score and enrichment value. The crucial features of the known inhibitors were evaluated by the online ZINC Pharmer to identify new leads from a ZINC database...
December 27, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29164496/correction-to-opicapone-a-review-in-parkinson-s-disease
#9
Lesley J Scott
Parkinson's disease (PD) is the most common chronic, progressive, neurodegenerative disease, with a mean age of onset of 57 years [1, 2].
January 2018: Drugs
https://www.readbyqxmd.com/read/28916530/elucidation-of-the-impact-of-p-glycoprotein-and-breast-cancer-resistance-protein-on-the-brain-distribution-of-catechol-o-methyltransferase-inhibitors
#10
Joana Bicker, Ana Fortuna, Gilberto Alves, Patricio Soares-da-Silva, Amilcar Falcao
P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are clinically important efflux transporters that act cooperatively at the blood-brain barrier, limiting the entry of several drugs into the CNS and affecting their pharmacokinetics, therapeutic efficacy and safety. In the present study, the interactions of catechol-O-methyltransferase (COMT) inhibitors (BIA 9-1059, BIA 9-1079, entacapone, nebicapone, opicapone and tolcapone) with P-gp and BCRP were investigated in order to determine the contribution of these transporters in their access to the brain...
September 15, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28734868/a-single-and-multiple-dose-study-to-investigate-the-pharmacokinetics-and-pharmacodynamics-of-opicapone-a-novel-comt-inhibitor-in-rat
#11
Daniela Gonçalves, Gilberto Alves, Ana Fortuna, Maria João Bonifácio, Patrício Soares-da-Silva, Amílcar Falcão
Opicapone is a novel catechol-O-methyltransferase (COMT) inhibitor that emerged to fulfil the need of a safer and more efficacious COMT inhibitor. The present study was carried out in order to assess and compare the pharmacokinetics and pharmacodynamics (COMT inhibition) of opicapone after single and multiple oral administrations (30 mg/kg) to Wistar rats. For this purpose, at predefined time points up to 72 h post-dosing, blood, liver and kidneys were collected and, then, the concentrations of opicapone and its active metabolite (BIA 9-1079) were determined in plasma and in liver and kidney tissues, as well as the erythrocyte, liver and kidney COMT activity...
July 19, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28580819/opicapone-for-the-management-of-end-of-dose-motor-fluctuations-in-patients-with-parkinson-s-disease-treated-with-l-dopa
#12
Andrew J Lees, Joaquim Ferreira, Olivier Rascol, Heinz Reichmann, Fabrizio Stocchi, Eduardo Tolosa, Werner Poewe
Opicapone is a third generation, highly potent and effective catechol O‑methyltransferase (COMT) inhibitor that optimizes the pharmacokinetics and bioavailability of L-DOPA therapy. Areas covered: In this review, the authors describe the preclinical and clinical development of opicapone. In PD patients with motor fluctuations, once daily opicapone administration was well-tolerated and consistently reduced OFF-time and increased ON-time without increasing the frequency of troublesome dyskinesia, and these benefits were maintained over at least a year of continued open-label therapy...
July 2017: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/28531266/concerns-regarding-opicapone-as-adjunct-to-levodopa-therapy-reply
#13
Andrew J Lees, José-Francisco Rocha, Patricio Soares-da-Silva
No abstract text is available yet for this article.
July 1, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28531250/concerns-regarding-opicapone-as-adjunct-to-levodopa-therapy
#14
Yu Zhang, Xiaoming Huang
No abstract text is available yet for this article.
July 1, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28322896/pharmacokinetics-of-opicapone-a-third-generation-comt-inhibitor-after-single-and-multiple-oral-administration-a-comparative-study-in-the-rat
#15
COMPARATIVE STUDY
Daniela Gonçalves, Gilberto Alves, Ana Fortuna, Patrício Soares-da-Silva, Amílcar Falcão
Opicapone is a novel potent, reversible and purely peripheral catechol-O-methyltransferase inhibitor that has been developed to be used as an adjunct to levodopa/aromatic L-amino acid decarboxylase inhibitor therapy for Parkinson's disease. Thus, this study aimed to compare the plasma pharmacokinetics of opicapone and its active metabolite (BIA 9-1079) after the administration of single and multiple oral doses to rats. Wistar rats (n=8 per group) were orally treated with single (30, 60 or 90mg/kg) or multiple (30mg/kg once-daily for seven consecutive days) oral doses of opicapone...
May 15, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28123288/spotlight-on-opicapone-as-an-adjunct-to-levodopa-in-parkinson-s-disease-design-development-and-potential-place-in-therapy
#16
REVIEW
Ádám Annus, László Vécsei
Parkinson's disease (PD) is a progressive, chronic, neurodegenerative disease characterized by rigidity, tremor, bradykinesia and postural instability secondary to dopaminergic deficit in the nigrostriatal system. Currently, disease-modifying therapies are not available, and levodopa (LD) treatment remains the gold standard for controlling motor and nonmotor symptoms of the disease. LD is extensively and rapidly metabolized by peripheral enzymes, namely, aromatic amino acid decarboxylase and catechol-O-methyltransferase (COMT)...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28027332/opicapone-as-adjunct-to-levodopa-therapy-in-patients-with-parkinson-disease-and-motor-fluctuations-a-randomized-clinical-trial
#17
RANDOMIZED CONTROLLED TRIAL
Andrew J Lees, Joaquim Ferreira, Olivier Rascol, Werner Poewe, José-Francisco Rocha, Michelle McCrory, Patricio Soares-da-Silva
Importance: Catechol O-methyltransferase (COMT) inhibitors are an established treatment for end-of-dose motor fluctuations associated with levodopa therapy in patients with Parkinson disease (PD). Current COMT inhibitors carry a high risk for toxic effects to hepatic cells or show moderate improvement. Opicapone was designed to be effective without the adverse effects. Objective: To evaluate the efficacy and safety of 25- and 50-mg/d dosages of opicapone compared with placebo as adjunct to levodopa therapy in patients with PD experiencing end-of-dose motor fluctuations...
February 1, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28027328/opicapone-a-novel-adjunct-for-an-old-standard
#18
Allison Boyle, Jessika Suescun, Mya C Schiess
No abstract text is available yet for this article.
February 1, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/27763682/effect-of-opicapone-multiple-dose-regimens-on-levodopa-pharmacokinetics
#19
RANDOMIZED CONTROLLED TRIAL
José-Francisco Rocha, Éric Sicard, Nicolas Fauchoux, Amílcar Falcão, Ana Santos, Ana I Loureiro, Roberto Pinto, Maria João Bonifácio, Teresa Nunes, Luís Almeida, Patrício Soares-da-Silva
AIMS: To compare the levodopa/carbidopa (LC) and levodopa/benserazide (LB) pharmacokinetic profiles following repeated doses of opicapone (OPC) administered apart from levodopa. METHODS: Two randomized, double blind, sex-balanced, placebo-controlled studies in four groups of 12 or 18 healthy subjects each. In each group, enrolled subjects received a once-daily morning (5, 15 and 30 mg) or evening (5, 15 and 50 mg) administration of OPC or placebo for up to 28 days...
March 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27599671/clinical-pharmacology-review-of-opicapone-for-the-treatment-of-parkinson-s-disease
#20
REVIEW
Margherita Fabbri, Mario M Rosa, Joaquim J Ferreira
Two catechol-O-methyl transferase inhibitors are currently used as add-on therapy to levodopa for the amelioration of end-of-dose motor fluctuations in Parkinson's disease patients: entacapone, which has moderate efficacy and requires multiple dosing, and tolcapone, which has a poor safety profile. Opicapone (OPC) is a novel, long-acting, peripherally selective, once daily, third-generation catechol-O-methyl transferase inhibitor. Two Phase III clinical trials demonstrated OPC efficacy in reducing OFF-time by an average of about 60 min daily compared with placebo, without increasing ON-time with troublesome dyskinesias, with a good drug safety profile...
October 2016: Neurodegenerative Disease Management
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