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Catechol-O-methyltransferase (COMT) metabolizes a portion of administered levodopa and thus makes it unavailable for conversion to dopamine in the brain. In an open-label trail, we examined the effects of entacapone, a peripheral inhibitor of COMT, administered acutely or for 8 weeks, on the pharmacokinetics and pharmacodynamics of levodopa in 15(More)
BACKGROUND Parkinson disease (PD) is a degenerative neurological disorder for which no treatment has been shown to slow the progression. OBJECTIVE To determine whether a range of dosages of coenzyme Q10 is safe and well tolerated and could slow the functional decline in PD. DESIGN Multicenter, randomized, parallel-group, placebo-controlled,(More)
OBJECTIVE To quantify the effects of deep brain stimulation (DBS) of globus pallidus interna (GPi) and subthalamic nucleus (STN) on motor fluctuations and dyskinesia in PD and to determine how the response to levodopa was modified by DBS. BACKGROUND Patients report that DBS reduces levodopa-induced motor fluctuations and dyskinesia throughout the day, but(More)
To determine how the response to levodopa is altered by long-term therapy, we examined the dose response to 2-hour infusions of levodopa in three groups of parkinsonian patients: those who were previously untreated, those who exhibited stable responses, and those who exhibited fluctuating responses to levodopa therapy, using tapping speed as an index of(More)
The short-duration response, long-duration response, and dyskinetic response to levodopa change during long-term levodopa therapy. How these responses evolve, and which changes contribute to the emergence of motor fluctuations, remain unclear. We studied 18 subjects with Parkinson's disease before they began levodopa therapy and after 6, 12, 24, and 48(More)
To determine whether tolerance to the antiparkinsonian actions of levodopa develops during longterm levodopa therapy, we compared the response to 2-hour levodopa infusions before and after 2- to 4-day levodopa holidays using tapping and walking speeds and tremor/dyskinesia scores as measures of response in 17 parkinsonian patients with a fluctuating(More)
Pilot data on mood and anxiety changes in 15 Parkinson's disease patients with motor fluctuations are described based on ratings every 30 min for 5 h bracketing a 2-h constant-rate levodopa infusion. Robust mood and anxiety effects slightly preceded but temporally paralleled fluctuations in motor tapping scores. Research nurse ratings blind to patient(More)
The cause of motor fluctuations occurring during constant-rate levodopa infusions is unknown. We examined whether known pharmacokinetic factors could explain the fluctuations and looked for clues to pharmacodynamic causes. Eleven subjects with stage III-V Parkinson's disease (PD) and a fluctuating response to levodopa underwent constant-rate infusions for(More)
The authors investigated the ability of daytime infusions of apomorphine, a D-1 and D-2 dopamine agonist, to sustain the long-duration response (LDR) in seven subjects with fluctuating PD in whom L-DOPA was discontinued for 3 days. Apomorphine maintained the LDR to the extent that it kept the subjects "on" during the day. This observation suggests that the(More)