caa a22 4500 445376627 CHVBK 20180317143004.0 cr unu---uuuuu 170323e20111201xx s 000 0 eng 10.1007/s00702-011-0703-9 doi (NATIONALLICENCE)springer-10.1007/s00702-011-0703-9 Continuous drug delivery in early- and late-stage Parkinson's disease as a strategy for avoiding dyskinesia induction and expression [Elektronische Daten] [P. Jenner, A. McCreary, D. Scheller] The treatment of the motor symptoms of Parkinson's disease (PD) is dependent on the use of dopamine replacement therapy in the form of l-dopa and dopamine agonist drugs. However, the development of dyskinesia (chorea, dystonia, athetosis) can become treatment limiting. The initiation of dyskinesia involves a priming process dependent on the presence of nigral dopaminergic cell loss leading to alterations in basal ganglia function that underlie the expression of involuntary movements following the administration of each drug dose. Once established, dyskinesia is difficult to control and it is even more difficult to reverse the priming process. Dyskinesia is more commonly induced by l-dopa than by dopamine agonist drugs. This has been associated with the short duration of l-dopa causing pulsatile stimulation of postsynaptic dopamine receptors compared to the longer acting dopamine agonists that cause more continuous stimulation. As a result, the concept of continuous dopaminergic stimulation (CDS) has arisen and has come to dominate the strategy for treatment of early PD. However, CDS has flaws that have led to the general acceptance that continuous drug delivery (CDD) is key to the successful treatment of PD. Studies in both experimental models of PD and in clinical trials have shown CDD to improve efficacy, but reduce dyskinesia induction, and to reverse established involuntary movements. Two key clinical strategies currently address the concept of CDD: (1) in early-, mid- and late-stage PD, transdermal administration of rotigotine provides 24h of drug delivery; (2) in late-stage PD, the constant intraduodenal administration of l-dopa is utilized to improve control of motor symptoms and to diminish established dyskinesia. This review examines the rationale for CDD and explores the clinical benefit of using such a strategy for the treatment of patients with PD. Springer-Verlag, 2011 CDS nationallicence CDD nationallicence L -dopa nationallicence Rotigotine nationallicence Duodopa nationallicence Dyskinesia nationallicence Jenner P. Neurodegenerative Disease Research Group, Institute of Pharmaceutical Sciences, School of Biomedical Sciences, King's College, London, UK aut McCreary A. Brains On-Line, Groningen, The Netherlands aut Scheller D. UCB Pharma, Allée de la Recherche, 60, 1070, Brussels, Belgium aut Journal of Neural Transmission Springer Vienna 118/12(2011-12-01), 1691-1702 0300-9564 118:12<1691 2011 118 702 https://doi.org/10.1007/s00702-011-0703-9 text/html Onlinezugriff via DOI 1 review-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00702-011-0703-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Jenner P. Neurodegenerative Disease Research Group, Institute of Pharmaceutical Sciences, School of Biomedical Sciences, King's College, London, UK aut NATIONALLICENCE 700 1- McCreary A. Brains On-Line, Groningen, The Netherlands aut NATIONALLICENCE 700 1- Scheller D. UCB Pharma, Allée de la Recherche, 60, 1070, Brussels, Belgium aut NATIONALLICENCE 773 0- Journal of Neural Transmission Springer Vienna 118/12(2011-12-01), 1691-1702 0300-9564 118:12<1691 2011 118 702 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer