Why do‘OFF’periods still occur during continuous drug delivery in Parkinson’s disease?  

作　　者：Silvia Rota Daniele Urso Daniel J.van Wamelen Valentina Leta Iro Boura Per Odin Alberto J.Espay Peter Jenner K.Ray Chaudhuri 

机构地区：[1]Department of Basic and Clinical Neurosciences,Institute of Psychiatry,Psychology and Neuroscience,King’s College London,London,UK [2]Parkinson’s Foundation Centre of Excellence,King’s College Hospital,London,UK [3]Department of Neuroimaging,Institute of Psychiatry,Psychology and Neuroscience,King’s College London,London,UK [4]Centre for Neurodegenerative Diseases and the Aging Brain,Department of Clinical Research in Neurology,University of Bari‘Aldo Moro,“Pia Fondazione Cardinale G.Panico”,73039 Tricase,Italy [5]Donders Institute for Brain,Cognition and Behaviour,Department of Neurology,Radboud University Medical Centre,Nijmegen,The Netherlands [6]School of Medicine,University of Crete,Crete,Greece [7]Department of Neurology,University Hospital of Heraklion,Crete,Greece [8]Division of Neurology,Department of Clinical Sciences Lund,Lund University,Lund,Sweden [9]University of Cincinnati Gardner Neuroscience Institute,Gardner Family Center for Parkinson’s Disease and Movement Disorders,Department of Neurology,University of Cincinnati,Cincinnati,OH,USA [10]Institute of Pharmaceutical Sciences,Faculty of Life Science and Medicine,King’s College London,London,UK.

出　　处：《Translational Neurodegeneration》2022年第1期280-293,共14页转化神经变性病（英文）

摘　　要：Continuous drug delivery(CDD)is used in moderately advanced and late-stage Parkinson’s disease(PD)to control motor and non-motor fluctuations(‘OFF’periods).Transdermal rotigotine is indicated for early fluctuations,while subcutaneous apomorphine infusion and levodopa-carbidopa intestinal gel are utilised in advanced PD.All three strategies are considered examples of continuous dopaminergic stimulation achieved through CDD.A central premise of the CDD is to achieve stable control of the parkinsonian motor and non-motor states and avoid emergence of‘OFF’periods.However,data suggest that despite their efficacy in reducing the number and duration of‘OFF’periods,these strategies still do not prevent‘OFF’periods in the middle to late stages of PD,thus contradicting the widely held concepts of continuous drug delivery and continuous dopaminergic stimulation.Why these emergent‘OFF’periods still occur is unknown.In this review,we analyse the potential reasons for their persistence.The contribution of drug-and device-related involvement,and the problems related to site-specific drug delivery are analysed.We propose that changes in dopaminergic and non-dopaminergic mechanisms in the basal ganglia might render these persistent‘OFF’periods unresponsive to dopaminergic therapy delivered via CDD.

关 键 词：‘OFF’periods Continuous drug delivery Continuous dopaminergic stimulation Rotigotine patch Subcutaneous apomorphine infusion Levodopa-carbidopa intestinal gel 

分 类 号：R742.5[医药卫生—神经病学与精神病学]