Common Noradrenergic Mechanisms in Parkinson´s Disease and L-DOPA Induced Dyskinesia
Status:
Unknown status
Trial end date:
2016-01-01
Target enrollment:
Participant gender:
Summary
The aims of this proposal include tests of hypotheses of the pathogenetic mechanisms of
noradrenergic neurotransmission in Parkinson's disease in vivo, using positron emission
tomography of patients with early and advanced Parkinson's disease with or without 3,4
L-dihydroxyphenylalanine (L-DOPA) - induced dyskinesia or co-morbid depression, and
evaluation of whether these mechanisms can be influenced therapeutically.
Hypotheses:
1. The investigators argue that release in human cortical and subcortical brain regions of
norepinephrine (NE) derived from metabolism of exogenousL-DOPA is greater in Parkinson's
disease patients with L-DOPA- induced dyskinesia than in patients without this
complication. This hypothesis will be tested by measuring antagonist [11C]yohimbine
binding to alpha-2 adrenoceptors before and after L-DOPA challenge.
2. If so, it is argued that the greater rise of norepinephrine, measured as [11C]yohimbine
displacement after L-DOPA challenge, is the result of down-regulation or loss of
norepinephrine transporters. This hypothesis will be tested by measuring the binding of
[11C]MeNER, a tracer of norepinephrine transporters.
3. If so, the investigators argue that the greater decline of [11C]MeNER binding is
significantly correlated to the symptoms of Parkinson's disease, as proof that patients
with more severe loss of noradrenergic terminals exhibit more severe motor deficits.
Details
Lead Sponsor:
Aarhus University Hospital
Collaborator:
University of Copenhagen
Treatments:
Carbidopa, levodopa drug combination Levodopa Yohimbine