Combined 5-HT1A and 5-HT1B receptor agonists for the treatment of L-DOPA-induced dyskinesia.

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Munoz, AnaLund University,Lunds universitet,Neurobiologi,Forskargrupper vid Lunds universitet,Neurobiology,Lund University Research Groups (författare)

Combined 5-HT1A and 5-HT1B receptor agonists for the treatment of L-DOPA-induced dyskinesia.

Artikel/kapitelEngelska2008

Förlag, utgivningsår, omfång ...

2008-10-24
Oxford University Press (OUP),2008

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LIBRIS-ID:oai:lup.lub.lu.se:83b2fe99-549f-4bbd-b750-fc7ec81dc032
https://lup.lub.lu.se/record/1261923URI
https://doi.org/10.1093/brain/awn235DOI

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Språk:engelska
Sammanfattning på:engelska

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Ämneskategori:art swepub-publicationtype
Ämneskategori:ref swepub-contenttype

Anmärkningar

Appearance of dyskinesia is a common problem of long-term l-DOPA treatment in Parkinson's disease patients and represents a major limitation for the pharmacological management of the motor symptoms in advanced disease stages. We have recently demonstrated that dopamine released from serotonin neurons is responsible for l-DOPA-induced dyskinesia in 6-hydroxydopamine (6-OHDA)-lesioned rats, raising the possibility that blockade of serotonin neuron activity by combination of 5-HT(1A) and 5-HT(1B) agonists could reduce l-DOPA-induced dyskinesia. In the present study, we have investigated the efficacy of 5-HT(1A) and 5-HT(1B) agonists to counteract l-DOPA-induced dyskinesia in 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine (MPTP)-treated macaques, the gold standard model of Parkinson's disease. In addition, we have studied the ability of this treatment to prevent development of l-DOPA-induced dyskinesia in 6-OHDA-lesioned rats. The results demonstrate the existence of a potent synergistic effect between 5-HT(1A) and 5-HT(1B) agonists in their ability to dampen l-DOPA-induced dyskinesia in the MPTP-treated macaques. Sub-threshold doses of the drugs, which individually produced no effect, were able to reduce the abnormal involuntary movements by up to 80% when administered in combination, without affecting the anti-parkinsonian properties of l-DOPA. Furthermore, chronic administration of low doses of the 5-HT(1) agonists in combination was able to prevent development of dyskinesia, and reduce the up-regulation of FosB after daily treatment with l-DOPA in the rat 6-OHDA model. Our results support the importance of a clinical investigation of the effect of 5-HT(1A) and 5-HT(1B) agonists, particularly in combination, in dyskinetic l-DOPA-treated Parkinson's disease patients.

Ämnesord och genrebeteckningar

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Neurologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Neurology hsv//eng
L-DOPA
Dyskinesia
Serotonin agonists
Parkinson's disease
MPTP
monkeys

Biuppslag (personer, institutioner, konferenser, titlar ...)

Li, Qin (författare)
Gardoni, Fabrizio (författare)
Marcello, Elena (författare)
Qin, Chuan (författare)
Carlsson, ThomasLund University,Lunds universitet,Brain Repair and Imaging in Neural Systems (BRAINS),Forskargrupper vid Lunds universitet,Lund University Research Groups(Swepub:lu)mphy-tka (författare)
Kirik, DenizLund University,Lunds universitet,Brain Repair and Imaging in Neural Systems (BRAINS),Forskargrupper vid Lunds universitet,Lund University Research Groups(Swepub:lu)mphy-dki (författare)
Luca, Monica Di (författare)
Björklund, AndersLund University,Lunds universitet,Neurobiologi,Forskargrupper vid Lunds universitet,Neurobiology,Lund University Research Groups(Swepub:lu)mphy-abj (författare)
Bezard, Erwan (författare)
Carta, ManoloLund University,Lunds universitet,Brain Repair and Imaging in Neural Systems (BRAINS),Forskargrupper vid Lunds universitet,Neurobiologi,Lund University Research Groups,Neurobiology(Swepub:lu)med-mca (författare)
NeurobiologiForskargrupper vid Lunds universitet (creator_code:org_t)

Sammanhörande titlar

Ingår i:Brain: Oxford University Press (OUP)131, s. 3380-33941460-21560006-8950

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Av författaren/redakt...: Munoz, Ana; Li, Qin; Gardoni, Fabrizi ...; Marcello, Elena; Qin, Chuan; Carlsson, Thomas; visa fler...; Kirik, Deniz; Luca, Monica Di; Björklund, Ander ...; Bezard, Erwan; Carta, Manolo; visa färre...

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Neurologi

Artiklar i publikationen: Brain

Av lärosätet: Lunds universitet

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