Delving into the Latest Updates on Nebicapone with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

COMT

Mechanism

COMT inhibitors(Catechol-O-methyl transferase inhibitors)

Therapeutic Areas

Nervous System DiseasesEndocrinology and Metabolic Disease

Active Indication-

Inactive Indication

Parkinson Disease

Originator Organization

BIAL-Portela & Cia SA

Active Organization-

Inactive Organization

BIAL-Portela & Cia SA

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC14H11NO5

InChIKeyMRFOLGFFTUGAEB-UHFFFAOYSA-N

CAS Registry274925-86-9

The purpose of this study was to investigate the effect on the "wearing-off" phenomenon of 3 different doses of nebicapone (NEB 50 mg, 100 mg and 150 mg), compared with entacapone and placebo when dministered concomitantly with existing treatment with levodopa plus a dopa decarboxylase inhibitor (DDCI: carbidopa or benserazide).

Start Date26 Sep 2006

Sponsor / Collaborator

BIAL-Portela & Cia SA

NCT02779348 / CompletedPhase 1

Effect of BIA 3-202 on the Pharmacokinetics and Pharmacodynamics of Warfarin in Healthy Volunteers

The purpose of this study is to determine whether multiple-dose administration of nebicapone affects the pharmacokinetics of warfarin.

Start Date01 Sep 2006

Sponsor / Collaborator

BIAL-Portela & Cia SA

EUCTR2006-001793-24-AT / Not yet recruitingNot Applicable

A MULTICENTRE, DOUBLE-BLIND, RANDOMIZED, ACTIVE- AND PLACEBO-CONTROLLED TRIAL TO INVESTIGATE THE EFFICACY AND TOLERABILITY OF NEBICAPONE IN PARKINSON’S DISEASE PATIENTS WITH WEARING-OFF” PHENOMENON TREATED WITH LEVODOPA/CARBIDOPA OR LEVODOPA/BENSERAZIDE - not available

Start Date31 Jul 2006

Sponsor / Collaborator-

100 Clinical Results associated with Nebicapone

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100 Translational Medicine associated with Nebicapone

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100 Patents (Medical) associated with Nebicapone

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28

Literatures (Medical) associated with Nebicapone

01 Feb 2022·Drug Metabolism and PharmacokineticsQ4 · MEDICINE

Investigation of the role and quantitative impact of breast cancer resistance protein on drug distribution into brain and CSF in rats

Q4 · MEDICINE

Article

Author: Tadano, Jun ; Kawaguchi, Hiroko ; Umemura, Koji ; Takano, Mikihisa ; Miyawaki, Izuru ; Katagiri, Yuki

Breast cancer resistance protein (BCRP) expressed in the blood-brain barrier plays a major role in limiting drug distribution into the central nervous system (CNS). However, functional involvement of BCRP in drug distribution into the brain and cerebrospinal fluid (CSF) remains unclear. The aim of present study was to reveal the role and quantitative impact of BCRP on CNS distribution. The brain-to-plasma unbound concentration ratio (K_p,uu,brain) and CSF-to-plasma unbound concentration ratio (K_p,uu,CSF) values of BCRP-specific substrates were determined in rats. The K_p,uu,brain values decreased, as the in vitro BCRP corrected flux ratio (CFR) increased. The K_p,uu,CSF values of BCRP-specific substrates were greater than the K_p,uu,brain values. Increase in the K_p,uu,brain values induced by co-administration of BCRP inhibitor correlated with the in vitro BCRP CFR and were greater than the increase in K_p,uu,CSF values induced by BCRP inhibitor except nebicapone. The contribution of BCRP to the brain and CSF distribution of the dual P-glycoprotein/BCRP substrates, imatinib and prazosin, was similar to that of BCRP-specific substrates. Thus, we revealed that the impact of in vivo BCRP on CNS distribution is correlated with in vitro BCRP CFR, and that BCRP limits drug distribution into the brain more strongly than into the CSF.

01 Dec 2017·Drug Metabolism and DispositionQ2 · MEDICINE

Elucidation of the Impact of P-glycoprotein and Breast Cancer Resistance Protein on the Brain Distribution of Catechol-O-Methyltransferase Inhibitors

Q2 · MEDICINE

Article

Author: Bicker, Joana ; Falcão, Amílcar ; Alves, Gilberto ; Fortuna, Ana ; Soares-da-Silva, Patrício

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 central nervous system (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 to determine the contribution of these transporters in their access to the brain. In vitro cellular accumulation and bidirectional transport assays were conducted in Madin-Darby canine kidney (MDCK) II, MDCK-MDR1, and MDCK-BCRP cells. In vivo pharmacokinetic studies were carried out for tolcapone and BIA 9-1079 in rats, with and without elacridar, a well-known P-gp and BCRP modulator. The results suggest that BIA 9-1079, nebicapone, and tolcapone inhibit BCRP in a concentration-dependent manner. Moreover, with net flux ratios higher than 2 and decreased over 50% in the presence of verapamil or Ko143, BIA 9-1079 was identified as a P-gp substrate while BIA 9-1059, entacapone, opicapone, and nebicapone were revealed to be BCRP substrates. In vivo, brain exposure was limited for tolcapone and BIA 9-1079, although tolcapone crossed the blood-brain barrier at a greater rate and to a greater extent than BIA 9-1079. The extent of brain distribution of both compounds was significantly increased in the presence of elacridar, attesting to the involvement of efflux transporters. These findings provide relevant information and improve the understanding of the mechanisms that govern the access of these COMT inhibitors to the CNS.

01 Jul 2012·Clinical NeuropharmacologyQ4 · MEDICINE

A Systematic Review of Catechol-O-Methyltransferase Inhibitors

Q4 · MEDICINE

Review

Author: Ceravolo, Roberto ; Marsala, Sandro Zambito ; Gioulis, Manuela ; Tinazzi, Michele

Catechol-O-methyltransferase (COMT) inhibitors are drugs commonly used in the management of patients with Parkinson disease complicated by motor fluctuations. Among them, entacapone is the most commonly used. Tolcapone has been reintroduced in patients where entacapone has proved to be ineffective after being withdrawn from the market because of sporadic cases of hepatotoxicity. The last COMT inhibitor is nebicapone, which use in clinical practice is still under study.OBJECTIVESThe objectives of this study were to analyze the clinical efficacy in reducing motor complications and to evaluate their use in clinical practice and the adverse events reported in the literature.METHODSScientific articles of the main previously mentioned drugs have been reviewed.RESULTSAll these 3 drugs have proved to be effective in improving wearing-off and significantly reduce the daily dose of levodopa at the number of daily intakes. Tolcapone is undoubtedly the most effective drug, although in clinical practice sporadic cases of hepatotoxicity have limited its use in patients unresponsive to entacapone. Nebicapone is effective, and its safety is still under evaluation. Entacapone is generally well tolerated, and no significant adverse events are reported.CONCLUSIONSTo manage motor fluctuations, the use of COMT inhibitors is now consolidated in the common clinical practice. Tolcapone is used as a second choice in patients with severe motor fluctuations not responsive to entacapone.

100 Deals associated with Nebicapone

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