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Drug insight: Continuous dopaminergic stimulation in the treatment of Parkinson's disease.
Nat Clin Pract Neurol. 2006 Jul; 2(7):382-92.NC

Abstract

Continuous dopaminergic stimulation is a therapeutic strategy for the management of Parkinson's disease, which proposes that dopaminergic agents that provide continuous stimulation of striatal dopamine receptors will delay or prevent the onset of levodopa-related motor complications. Dopaminergic neurons in the basal ganglia normally fire in a random but continuous manner, so that striatal dopamine concentrations are maintained at a relatively constant level. In the dopamine-depleted state, however, intermittent oral doses of levodopa induce discontinuous stimulation of striatal dopamine receptors. This pulsatile stimulation leads to molecular and physiologic changes in basal ganglia neurons and the development of motor complications. These effects are reduced or avoided when dopaminergic therapies are delivered in a more continuous and physiologic manner. Studies in primate models and patients with Parkinson's disease have shown that continuous or long-acting dopaminergic agents are associated with a decreased risk of motor complications compared with short-acting dopamine agonists or levodopa formulations. Continuous dopaminergic stimulation can be achieved with a continuous infusion, but infusion therapies are cumbersome and not likely to be acceptable to patients with early disease. The current challenge is to develop a long-acting oral formulation of levodopa that provides comparable anti-parkinsonian benefits without motor complications.

Authors+Show Affiliations

Department of Neurology, Mount Sinai School of Medicine, New York, NY 10029, USA. warren.olanow@mssm.eduNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

16932589

Citation

Olanow, C Warren, et al. "Drug Insight: Continuous Dopaminergic Stimulation in the Treatment of Parkinson's Disease." Nature Clinical Practice. Neurology, vol. 2, no. 7, 2006, pp. 382-92.
Olanow CW, Obeso JA, Stocchi F. Drug insight: Continuous dopaminergic stimulation in the treatment of Parkinson's disease. Nat Clin Pract Neurol. 2006;2(7):382-92.
Olanow, C. W., Obeso, J. A., & Stocchi, F. (2006). Drug insight: Continuous dopaminergic stimulation in the treatment of Parkinson's disease. Nature Clinical Practice. Neurology, 2(7), 382-92.
Olanow CW, Obeso JA, Stocchi F. Drug Insight: Continuous Dopaminergic Stimulation in the Treatment of Parkinson's Disease. Nat Clin Pract Neurol. 2006;2(7):382-92. PubMed PMID: 16932589.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Drug insight: Continuous dopaminergic stimulation in the treatment of Parkinson's disease. AU - Olanow,C Warren, AU - Obeso,José A, AU - Stocchi,Fabrizio, PY - 2006/03/14/received PY - 2006/05/09/accepted PY - 2006/8/26/pubmed PY - 2006/9/16/medline PY - 2006/8/26/entrez SP - 382 EP - 92 JF - Nature clinical practice. Neurology JO - Nat Clin Pract Neurol VL - 2 IS - 7 N2 - Continuous dopaminergic stimulation is a therapeutic strategy for the management of Parkinson's disease, which proposes that dopaminergic agents that provide continuous stimulation of striatal dopamine receptors will delay or prevent the onset of levodopa-related motor complications. Dopaminergic neurons in the basal ganglia normally fire in a random but continuous manner, so that striatal dopamine concentrations are maintained at a relatively constant level. In the dopamine-depleted state, however, intermittent oral doses of levodopa induce discontinuous stimulation of striatal dopamine receptors. This pulsatile stimulation leads to molecular and physiologic changes in basal ganglia neurons and the development of motor complications. These effects are reduced or avoided when dopaminergic therapies are delivered in a more continuous and physiologic manner. Studies in primate models and patients with Parkinson's disease have shown that continuous or long-acting dopaminergic agents are associated with a decreased risk of motor complications compared with short-acting dopamine agonists or levodopa formulations. Continuous dopaminergic stimulation can be achieved with a continuous infusion, but infusion therapies are cumbersome and not likely to be acceptable to patients with early disease. The current challenge is to develop a long-acting oral formulation of levodopa that provides comparable anti-parkinsonian benefits without motor complications. SN - 1745-834X UR - https://www.unboundmedicine.com/medline/citation/16932589/Drug_insight:_Continuous_dopaminergic_stimulation_in_the_treatment_of_Parkinson's_disease_ L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=16932589.ui DB - PRIME DP - Unbound Medicine ER -