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mu Opioid Receptor ...
mu Opioid Receptor Agonism for L-DOPA-Induced Dyskinesia in Parkinson's Disease
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- Bezard, Erwan (författare)
- Univ Bordeaux, Inst Malad Neurodegenerat, Unite Mixte Rech 5293, F-33000 Bordeaux, France.;CNRS, Inst Malad Neurodegenerat, Unite Mixte Rech 5293, F-33000 Bordeaux, France.;Motac Neurosci, Manchester M15 6WE, Lancs, England.;China Acad Med Sci, Inst Lab Anim Sci, Beijing 100021, Peoples R China.
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- Li, Qin (författare)
- Motac Neurosci, Manchester M15 6WE, Lancs, England.;China Acad Med Sci, Inst Lab Anim Sci, Beijing 100021, Peoples R China.
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- Hulme, Heather (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för farmaceutisk biovetenskap
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- Fridjonsdottir, Elva (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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- Nilsson, Anna (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Science for Life Laboratory, SciLifeLab
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- Pioli, Elsa (författare)
- Motac Neurosci, Manchester M15 6WE, Lancs, England.
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- Andrén, Per E. (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Science for Life Laboratory, SciLifeLab
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- Crossman, Alan R. (författare)
- Motac Neurosci, Manchester M15 6WE, Lancs, England.
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Univ Bordeaux, Inst Malad Neurodegenerat, Unite Mixte Rech 5293, F-33000 Bordeaux, France;CNRS, Inst Malad Neurodegenerat, Unite Mixte Rech 5293, F-33000 Bordeaux, France.;Motac Neurosci, Manchester M15 6WE, Lancs, England.;China Acad Med Sci, Inst Lab Anim Sci, Beijing 100021, Peoples R China. Motac Neurosci, Manchester M15 6WE, Lancs, England.;China Acad Med Sci, Inst Lab Anim Sci, Beijing 100021, Peoples R China. (creator_code:org_t)
- Society for Neuroscience, 2020
- 2020
- Engelska.
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Ingår i: Journal of Neuroscience. - : Society for Neuroscience. - 0270-6474 .- 1529-2401. ; 40:35, s. 6812-6819
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Parkinson's disease (PD) is characterized by severe locomotor deficits and is commonly treated with the dopamine precursor L-DOPA, but its prolonged usage causes dyskinesias referred to as L-DOPA-induced dyskinesia (LID). Several studies in animal models of PD have suggested that dyskinesias are associated with a heightened opioid cotransmitter tone, observations that have led to the notion of a LID-related hyperactive opioid transmission that should be corrected by mu opioid receptor antagonists. Reports that both antagonists and agonists of the mu opioid receptor may alleviate LID severity in primate models of PD and LID, together with the failure of nonspecific antagonist to improve LID in pilot clinical trials in patients, raises doubt about the reliability of the available data on the opioid system in PD and LID. After in vitro characterization of the functional activity at the mu opioid receptor, we selected prototypical agonists, antagonists, and partial agonists at the mu opioid receptor. We then showed that both oral and discrete intracerebral administration of a mu receptor agonist, but not of an antagonist as long thought, ameliorated LIDs in the gold-standard bilateral 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridinelesioned female macaque model of PD and LID. The results call for a reappraisal of opioid pharmacology in the basal ganglia as well as for the development of brain nucleus-targeted mu opioid receptor agonists.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Nyckelord
- dyskinesia
- MALDI
- mu
- opioid
- primate
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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