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Serotonergic mechanisms responsible for levodopa-induced dyskinesias in Parkinson’s disease patients
by
Molloy, Sophie
, Piccini, Paola
, Wu, Kit
, Bain, Peter
, Kiferle, Lorenzo
, Loane, Clare
, Turkheimer, Federico E.
, Brooks, David J.
, Politis, Marios
in
Aged
/ Antiparkinson Agents - adverse effects
/ Antiparkinson Agents - therapeutic use
/ Biomedical research
/ Buspirone - pharmacology
/ Buspirone - therapeutic use
/ Case-Control Studies
/ Development and progression
/ Dopamine
/ Dopamine - metabolism
/ Double-Blind Method
/ Dyskinesia, Drug-Induced - diagnostic imaging
/ Dyskinesia, Drug-Induced - drug therapy
/ Dyskinesia, Drug-Induced - etiology
/ Female
/ Humans
/ Identification and classification
/ Levodopa - adverse effects
/ Levodopa - therapeutic use
/ Male
/ Middle Aged
/ Movement disorders
/ Parkinson Disease - diagnostic imaging
/ Parkinson Disease - drug therapy
/ Parkinson's disease
/ Physiological aspects
/ Properties
/ Putamen - diagnostic imaging
/ Putamen - metabolism
/ Raclopride
/ Radionuclide Imaging
/ Radiopharmaceuticals
/ Serotonergic Neurons - drug effects
/ Serotonergic Neurons - metabolism
/ Serotonin
/ Serotonin 5-HT1 Receptor Agonists - pharmacology
/ Serotonin 5-HT1 Receptor Agonists - therapeutic use
/ Studies
/ Synapses - diagnostic imaging
/ Synapses - metabolism
/ Treatment Outcome
/ Values
2014
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Serotonergic mechanisms responsible for levodopa-induced dyskinesias in Parkinson’s disease patients
by
Molloy, Sophie
, Piccini, Paola
, Wu, Kit
, Bain, Peter
, Kiferle, Lorenzo
, Loane, Clare
, Turkheimer, Federico E.
, Brooks, David J.
, Politis, Marios
in
Aged
/ Antiparkinson Agents - adverse effects
/ Antiparkinson Agents - therapeutic use
/ Biomedical research
/ Buspirone - pharmacology
/ Buspirone - therapeutic use
/ Case-Control Studies
/ Development and progression
/ Dopamine
/ Dopamine - metabolism
/ Double-Blind Method
/ Dyskinesia, Drug-Induced - diagnostic imaging
/ Dyskinesia, Drug-Induced - drug therapy
/ Dyskinesia, Drug-Induced - etiology
/ Female
/ Humans
/ Identification and classification
/ Levodopa - adverse effects
/ Levodopa - therapeutic use
/ Male
/ Middle Aged
/ Movement disorders
/ Parkinson Disease - diagnostic imaging
/ Parkinson Disease - drug therapy
/ Parkinson's disease
/ Physiological aspects
/ Properties
/ Putamen - diagnostic imaging
/ Putamen - metabolism
/ Raclopride
/ Radionuclide Imaging
/ Radiopharmaceuticals
/ Serotonergic Neurons - drug effects
/ Serotonergic Neurons - metabolism
/ Serotonin
/ Serotonin 5-HT1 Receptor Agonists - pharmacology
/ Serotonin 5-HT1 Receptor Agonists - therapeutic use
/ Studies
/ Synapses - diagnostic imaging
/ Synapses - metabolism
/ Treatment Outcome
/ Values
2014
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Serotonergic mechanisms responsible for levodopa-induced dyskinesias in Parkinson’s disease patients
by
Molloy, Sophie
, Piccini, Paola
, Wu, Kit
, Bain, Peter
, Kiferle, Lorenzo
, Loane, Clare
, Turkheimer, Federico E.
, Brooks, David J.
, Politis, Marios
in
Aged
/ Antiparkinson Agents - adverse effects
/ Antiparkinson Agents - therapeutic use
/ Biomedical research
/ Buspirone - pharmacology
/ Buspirone - therapeutic use
/ Case-Control Studies
/ Development and progression
/ Dopamine
/ Dopamine - metabolism
/ Double-Blind Method
/ Dyskinesia, Drug-Induced - diagnostic imaging
/ Dyskinesia, Drug-Induced - drug therapy
/ Dyskinesia, Drug-Induced - etiology
/ Female
/ Humans
/ Identification and classification
/ Levodopa - adverse effects
/ Levodopa - therapeutic use
/ Male
/ Middle Aged
/ Movement disorders
/ Parkinson Disease - diagnostic imaging
/ Parkinson Disease - drug therapy
/ Parkinson's disease
/ Physiological aspects
/ Properties
/ Putamen - diagnostic imaging
/ Putamen - metabolism
/ Raclopride
/ Radionuclide Imaging
/ Radiopharmaceuticals
/ Serotonergic Neurons - drug effects
/ Serotonergic Neurons - metabolism
/ Serotonin
/ Serotonin 5-HT1 Receptor Agonists - pharmacology
/ Serotonin 5-HT1 Receptor Agonists - therapeutic use
/ Studies
/ Synapses - diagnostic imaging
/ Synapses - metabolism
/ Treatment Outcome
/ Values
2014
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Serotonergic mechanisms responsible for levodopa-induced dyskinesias in Parkinson’s disease patients
Journal Article
Serotonergic mechanisms responsible for levodopa-induced dyskinesias in Parkinson’s disease patients
2014
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Overview
Levodopa-induced dyskinesias (LIDs) are the most common and disabling adverse motor effect of therapy in Parkinson's disease (PD) patients. In this study, we investigated serotonergic mechanisms in LIDs development in PD patients using 11C-DASB PET to evaluate serotonin terminal function and 11C-raclopride PET to evaluate dopamine release. PD patients with LIDs showed relative preservation of serotonergic terminals throughout their disease. Identical levodopa doses induced markedly higher striatal synaptic dopamine concentrations in PD patients with LIDs compared with PD patients with stable responses to levodopa. Oral administration of the serotonin receptor type 1A agonist buspirone prior to levodopa reduced levodopa-evoked striatal synaptic dopamine increases and attenuated LIDs. PD patients with LIDs that exhibited greater decreases in synaptic dopamine after buspirone pretreatment had higher levels of serotonergic terminal functional integrity. Buspirone-associated modulation of dopamine levels was greater in PD patients with mild LIDs compared with those with more severe LIDs. These findings indicate that striatal serotonergic terminals contribute to LIDs pathophysiology via aberrant processing of exogenous levodopa and release of dopamine as false neurotransmitter in the denervated striatum of PD patients with LIDs. Our results also support the development of selective serotonin receptor type 1A agonists for use as antidyskinetic agents in PD.
Publisher
American Society for Clinical Investigation
Subject
/ Antiparkinson Agents - adverse effects
/ Antiparkinson Agents - therapeutic use
/ Dopamine
/ Dyskinesia, Drug-Induced - diagnostic imaging
/ Dyskinesia, Drug-Induced - drug therapy
/ Dyskinesia, Drug-Induced - etiology
/ Female
/ Humans
/ Identification and classification
/ Male
/ Parkinson Disease - diagnostic imaging
/ Parkinson Disease - drug therapy
/ Putamen - diagnostic imaging
/ Serotonergic Neurons - drug effects
/ Serotonergic Neurons - metabolism
/ Serotonin 5-HT1 Receptor Agonists - pharmacology
/ Serotonin 5-HT1 Receptor Agonists - therapeutic use
/ Studies
/ Synapses - diagnostic imaging
/ Values
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