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LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00003538naa a2200373 4500
001oai:DiVA.org:uu-283251
003SwePub
008160412s2015 | |||||||||||000 ||eng|
009oai:prod.swepub.kib.ki.se:130684053
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-2832512 URI
0247 a https://doi.org/10.1007/s00702-014-1247-62 DOI
0247 a http://kipublications.ki.se/Default.aspx?queryparsed=id:1306840532 URI
040 a (SwePub)uud (SwePub)ki
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Malmlöf, Torun4 aut
2451 0a Deuterium-substituted L-DOPA displays increased behavioral potency and dopamine output in an animal model of Parkinson's disease :b comparison with the effects produced by L-DOPA and an MAO-B inhibitor.
264 c 2014-06-07
264 1b Springer Science and Business Media LLC,c 2015
338 a print2 rdacarrier
520 a 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.
7001 a Feltmann, Kristinu Karolinska Institutet4 aut
7001 a Konradsson-Geuken, Åsau Karolinska Institutet4 aut
7001 a Schneider, Frank4 aut
7001 a Alken, Rudolf-Giesbert4 aut
7001 a Svensson, Torgny Hu Karolinska Institutet4 aut
7001 a Schilström, Björnu Karolinska Institutet4 aut
7102 a Karolinska Institutet4 org
7730 t Journal of neural transmissiond : Springer Science and Business Media LLCg 122:2q 122:2x 0300-9564x 1435-1463
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-283251
8564 8u https://doi.org/10.1007/s00702-014-1247-6
8564 8u http://kipublications.ki.se/Default.aspx?queryparsed=id:130684053

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