Continuous cerebroventricular administration of dopamine: A new treatment for severe dyskinesia in Parkinson's disease?

Autor: Laloux C; Département de Pharmacologie médicale, INSERM UMRS-1171, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, 1 place de Verdun, 59045 Lille cedex, France., Gouel F; Département de Pharmacologie médicale, INSERM UMRS-1171, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, 1 place de Verdun, 59045 Lille cedex, France., Lachaud C; Département de Pharmacologie médicale, INSERM UMRS-1171, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, 1 place de Verdun, 59045 Lille cedex, France., Timmerman K; Département de Pharmacologie médicale, INSERM UMRS-1171, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, 1 place de Verdun, 59045 Lille cedex, France., Do Van B; Département de Pharmacologie médicale, INSERM UMRS-1171, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, 1 place de Verdun, 59045 Lille cedex, France., Jonneaux A; Département de Pharmacologie médicale, INSERM UMRS-1171, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, 1 place de Verdun, 59045 Lille cedex, France., Petrault M; Département de Pharmacologie médicale, INSERM UMRS-1171, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, 1 place de Verdun, 59045 Lille cedex, France., Garcon G; Institut Pasteur de Lille, EA4483-IMPECS, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, Lille, France., Rouaix N; Service de biochimie, dosage des catécholamines, et biologie moléculaire, CHRU de Lille, France., Moreau C; Département de Pharmacologie médicale, INSERM UMRS-1171, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, 1 place de Verdun, 59045 Lille cedex, France; Université de Lille, CHU de Lille, INSERM UMRS_1171, Service de Neurologie NS-Park/FCRIN Network LICEND COEN Center Lille, France., Bordet R; Département de Pharmacologie médicale, INSERM UMRS-1171, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, 1 place de Verdun, 59045 Lille cedex, France., Duce JA; School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, West Yorkshire, UK; Oxidation Biology Unit, The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia., Devedjian JC; Département de Pharmacologie médicale, INSERM UMRS-1171, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, 1 place de Verdun, 59045 Lille cedex, France., Devos D; Département de Pharmacologie médicale, INSERM UMRS-1171, Université Lille Nord de France, CHRU de Lille, Faculté de médecine, Pôle Recherche, 1 place de Verdun, 59045 Lille cedex, France; Université de Lille, CHU de Lille, INSERM UMRS_1171, Service de Pharmacologie Clinique et service de Neurologie LICEND COEN Center Lille, France. Electronic address: david.devos@chru-lille.fr.
Jazyk: angličtina
Zdroj: Neurobiology of disease [Neurobiol Dis] 2017 Jul; Vol. 103, pp. 24-31. Date of Electronic Publication: 2017 Mar 29.
DOI: 10.1016/j.nbd.2017.03.013
Abstrakt: In Parkinson's disease (PD) depletion of dopamine in the nigro-striatal pathway is a main pathological hallmark that requires continuous and focal restoration. Current predominant treatment with intermittent oral administration of its precursor, Levodopa (l-dopa), remains the gold standard but pharmacological drawbacks trigger motor fluctuations and dyskinesia. Continuous intracerebroventricular (i.c.v.) administration of dopamine previously failed as a therapy because of an inability to resolve the accelerated dopamine oxidation and tachyphylaxia. We aim to overcome prior challenges by demonstrating treatment feasibility and efficacy of continuous i.c.v. of dopamine close to the striatum. Dopamine prepared either anaerobically (A-dopamine) or aerobically (O-dopamine) in the presence or absence of a conservator (sodium metabisulfite, SMBS) was assessed upon acute MPTP and chronic 6-OHDA lesioning and compared to peripheral l-dopa treatment. A-dopamine restored motor function and induced a dose dependent increase of nigro-striatal tyrosine hydroxylase positive neurons in mice after 7days of MPTP insult that was not evident with either O-dopamine or l-dopa. In the 6-OHDA rat model, continuous circadian i.c.v. injection of A-dopamine over 30days also improved motor activity without occurrence of tachyphylaxia. This safety profile was highly favorable as A-dopamine did not induce dyskinesia or behavioral sensitization as observed with peripheral l-dopa treatment. Indicative of a new therapeutic strategy for patients suffering from l-dopa related complications with dyskinesia, continuous i.c.v. of A-dopamine has greater efficacy in mediating motor impairment over a large therapeutic index without inducing dyskinesia and tachyphylaxia.
(Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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