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Deuterium-substitut...
Deuterium-substituted L-DOPA displays increased behavioral potency and dopamine output in an animal model of Parkinson's disease : comparison with the effects produced by L-DOPA and an MAO-B inhibitor.
- Article/chapterEnglish2015
Publisher, publication year, extent ...
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2014-06-07
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Springer Science and Business Media LLC,2015
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-283251
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-283251URI
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https://doi.org/10.1007/s00702-014-1247-6DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:130684053URI
Supplementary language notes
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Language:English
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Summary in:English
Part of subdatabase
Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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The most effective treatment of Parkinson's disease (PD) L-DOPA is associated with major side effects, in particular L-DOPA-induced dyskinesia, which motivates development of new treatment strategies. We have previously shown that chronic treatment with a substantially lower dose of deuterium-substituted L-DOPA (D3-L-DOPA), compared with L-DOPA, produced equal anti-parkinsonian effect and reduced dyskinesia in 6-OHDA-lesioned rats. The advantageous effects of D3-L-DOPA are in all probability related to a reduced metabolism of deuterium dopamine by the enzyme monoamine oxidase (MAO). Therefore, a comparative neurochemical analysis was here performed studying the effects of D3-L-DOPA and L-DOPA on dopamine output and metabolism in 6-OHDA-lesioned animals using in vivo microdialysis. The effects produced by D3-L-DOPA and L-DOPA alone were additionally compared with those elicited when the drugs were combined with the MAO-B inhibitor selegiline, used in PD treatment. The different treatment combinations were first evaluated for motor activation; here the increased potency of D3-L-DOPA, as compared to that of L-DOPA, was confirmed and shown to be of equal magnitude as the effect produced by the combination of selegiline/L-DOPA. The extracellular levels of dopamine were also increased following both D3-L-DOPA and selegiline/L-DOPA administration compared with L-DOPA administration. The enhanced behavioral and neurochemical effects produced by D3-L-DOPA and the combination of selegiline/L-DOPA are attributed to decreased metabolism of released dopamine by MAO-B. The similar effect produced by D3-L-DOPA and selegiline/L-DOPA, respectively, is of considerable clinical interest since D3-L-DOPA, previously shown to exhibit a wider therapeutic window, in addition may reduce the need for adjuvant MAO-B inhibitor treatment.
Added entries (persons, corporate bodies, meetings, titles ...)
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Feltmann, KristinKarolinska Institutet
(author)
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Konradsson-Geuken, ÅsaKarolinska Institutet
(author)
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Schneider, Frank
(author)
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Alken, Rudolf-Giesbert
(author)
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Svensson, Torgny HKarolinska Institutet
(author)
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Schilström, BjörnKarolinska Institutet
(author)
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Karolinska Institutet
(creator_code:org_t)
Related titles
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In:Journal of neural transmission: Springer Science and Business Media LLC122:20300-95641435-1463
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