Effect of long-term therapy on the pharmacodynamics of levodopa. Relation to on-off phenomenon
J. G. Nutt, W. R. Woodward, J. H. Carter and S. T. Gancher
Department of Neurology, School of Medicine, Oregon Health Sciences University, Portland 97201-3098.
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
bradykinesia. The baseline tapping speed was greater in the patients with
stable responses than in the untreated patients, probably representing a
"long-duration response" to levodopa therapy. A "short-duration response,"
indicated by an increase in tapping speed lasting hours, was observed in
most patients in all groups. The onset of the short-duration effect was
more rapid and the incremental increase in tapping speed was twice as large
in the patients with fluctuating responses compared with the untreated
patients and patients with stable responses. The duration of the
short-duration effect was greatest in the untreated group but did not
differ between the groups with stable and fluctuating responses. Dyskinesia
was not observed in any of the de novo patients but was observed in three
of 12 patients with stable responses and eight of nine patients with
fluctuating responses to levodopa therapy. Dyskinesia appeared before or
with the antiparkinsonian effects in patients with stable responses, giving
no indication of a higher threshold for dyskinesia in these patients
compared with those with fluctuating responses. The plasma half-life
clearance, volume of distribution, and maximum plasma concentrations of
levodopa did not differ among groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Sprouting of dopamine terminals and altered dopamine release and uptake in Parkinsonian dyskinaesia
Lee et al.
Brain 2008;131:1574-1587.
ABSTRACT
| FULL TEXT
Evaluation of Levodopa Dose and Magnitude of Dopamine Depletion as Risk Factors for Levodopa-Induced Dyskinesia in a Rat Model of Parkinson's Disease
Putterman et al.
J. Pharmacol. Exp. Ther. 2007;323:277-284.
ABSTRACT
| FULL TEXT
Patterns of levodopa response in Parkinson's disease: a clinico-pathological study
Kempster et al.
Brain 2007;130:2123-2128.
ABSTRACT
| FULL TEXT
Levodopa-induced dyskinesia in Parkinson's disease: clinical features, pathogenesis, prevention and treatment
Thanvi et al.
Postgrad. Med. J. 2007;83:384-388.
ABSTRACT
| FULL TEXT
Clinical correlates of levodopa-induced dopamine release in Parkinson disease: a PET study.
Pavese et al.
Neurology 2006;67:1612-1617.
ABSTRACT
| FULL TEXT
The origin of motor fluctuations in Parkinson's disease: Importance of dopaminergic innervation and basal ganglia circuits
Obeso et al.
Neurology 2004;62:S17-30.
ABSTRACT
| FULL TEXT
The MPTP-treated primate as a model of motor complications in PD: Primate model of motor complications
Jenner
Neurology 2003;61:S4-11.
ABSTRACT
| FULL TEXT
Response to levodopa in parkinsonian patients with bilateral subthalamic nucleus stimulation
Moro et al.
Brain 2002;125:2408-2417.
ABSTRACT
| FULL TEXT
Relevance of motor complications in Parkinson's disease
Adler
Neurology 2002;58:S51-56.
ABSTRACT
| FULL TEXT
Response to Levodopa Treatment in Dopa-Responsive Dystonia
Nutt and Nygaard
Arch Neurol 2001;58:905-910.
ABSTRACT
| FULL TEXT
The long-duration response to L-dopa in the treatment of early PD
Zappia et al.
Neurology 2000;54:1910-1915.
ABSTRACT
| FULL TEXT
Vesicular Monoamine Transporter-2 and Aromatic L-Amino Acid Decarboxylase Enhance Dopamine Delivery after L-3,4-Dihydroxyphenylalanine Administration in Parkinsonian Rats
Lee et al.
J. Neurosci. 1999;19:3266-3274.
ABSTRACT
| FULL TEXT
Loss of long-duration response to levodopa over time in PD: Implications for wearing-off
Zappia et al.
Neurology 1999;52:763-763.
ABSTRACT
| FULL TEXT
