Multiple small doses of levodopa plus entacapone produce continuous dopaminergic stimulation and reduce dyskinesia induction in MPTP‐treated drug‐naïve primates
- 9 March 2005
- journal article
- research article
- Published by Wiley in Movement Disorders
- Vol. 20 (3), 306-314
- https://doi.org/10.1002/mds.20317
Abstract
Long-acting dopamine agonist drugs induce a lower incidence of dyskinesia in MPTP-treated primates and patients with Parkinson's disease compared to pulsatile treatment with levodopa, supporting the concept of continuous dopaminergic stimulation as a means of dyskinesia avoidance. We examined the effects of L-dopa administered with or without the COMT inhibitor entacapone on dyskinesia induction in previously untreated MPTP-treated common marmosets. Administration of L-dopa (12.5 mg/kg p.o.) plus carbidopa twice daily produced fluctuating improvement in motor behavior coupled with dyskinesia. Coadministration with entacapone produced similar patterns of motor improvement and dyskinesia that were not different from that produced by L-dopa alone. Treatment with L-dopa (6.25 mg/kg p.o.) plus carbidopa four times daily reversed motor disability and induced dyskinesia in a manner that was not different from the twice-daily treatment regimens. However, coadministration with entacapone produced more continuous improvement in locomotor activity with less dyskinesia than animals treated with L-dopa four times daily alone. These data support the notion that pulsatile stimulation contributes to the development of dyskinesia and suggests that more frequent dosing of L-dopa plus entacapone may be a useful treatment strategy for patients in the early stages of Parkinson's disease. © 2004 Movement Disorder SocietyKeywords
Funding Information
- Novartis AG
- Bendheim Parkinson Disease Centre
This publication has 31 references indexed in Scilit:
- Afferent modulation of dopamine neuron firing differentially regulates tonic and phasic dopamine transmissionNature Neuroscience, 2003
- Levodopa: why the controversy?The Lancet, 2002
- An algorithm (decision tree) for the management of Parkinson’s disease (2001):Neurology, 2001
- Continuous dopamine-receptor stimulation in early Parkinson's diseaseTrends in Neurosciences, 2000
- Pramipexole vs Levodopa as Initial Treatment for Parkinson DiseaseJAMA, 2000
- The tonic/phasic model of dopamine system regulation and its implications for understanding alcohol and psychostimulant cravingAddiction, 2000
- A Five-Year Study of the Incidence of Dyskinesia in Patients with Early Parkinson's Disease Who Were Treated with Ropinirole or LevodopaNew England Journal of Medicine, 2000
- De novo administration of ropinirole and bromocriptine induces less dyskinesia than L‐dopa in the MPTP‐treated marmosetMovement Disorders, 1998
- Chronic treatment withl-DOPA, but not bromocriptine induces dyskinesia in MPTP-parkinsonian monkeys. Correlation with [3H]spiperone bindingBrain Research, 1986
- "ON-OFF" EFFECTS IN PATIENTS WITH PARKINSON'S DISEASE ON CHRONIC LEVODOPA THERAPYThe Lancet, 1976