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ID 114098
Title Alternative
Intrastriatal Memantine Infusion
Author
Ogawa, Masatoshi Tokushima University
Zhou, Yu Tokushima University
Tsuji, Ryosuke Tokushima University
Keywords
intracerebral brain infusion
levodopa-induced dyskinesia
memantine
N-methyl-D-aspartate receptor
Parkinson’s disease
Content Type
Journal Article
Description
Although the administration of dopamine precursor levodopa remains as the mainstay for the treatment of Parkinson’s disease, long-term exposure to levodopa often causes a disabling complication, referred to as levodopa-induced dyskinesias. Therefore, the development of new therapeutic interventions to dampen levodopa-induced dyskinesias and parkinsonian motor deficits is needed in the treatment of Parkinson’s disease. Intracerebral brain infusion has the merit of being able to specifically deliver any drug into any brain part. By using an intracerebral infusion system equipped with implantable, programmable, and refillable pumps, we show herein that continuous intrastriatal administration of memantine (MMT), which is a non-competitive N-methyl-D-aspartate receptor antagonist, attenuates levodopa-induced dyskinesias and parkinsonian signs in 6-hydroxydopamine-lesioned hemiparkinsonian mice that received daily levodopa treatment. Corroborating the general thought that overactivation of the striatal N-methyl-D-aspartate receptor function might generate levodopa-induced dyskinesias and parkinsonism, our results suggest that a continuous intrastriatal MMT infusion can be beneficial for the management of Parkinson’s disease with levodopa-induced dyskinesias. Our study also provides indications for the prototypic use of pharmacological deep-brain modulation through intracerebral infusion systems for treating medically intractable movement disorders.
Journal Title
Frontiers in Neurology
ISSN
16642295
Publisher
Frontiers
Volume
10
Start Page
1258
Published Date
2019-12-05
Rights
© 2019 Ogawa, Zhou, Tsuji, Kasahara and Goto. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY)(https://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
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language
eng
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departments
Pharmaceutical Sciences
Medical Sciences