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Continuous dopamine-receptor treatment of Parkinson's disease: scientific rationale and clinical implications.
Lancet Neurol. 2006 Aug; 5(8):677-87.LN

Abstract

Levodopa-induced motor complications are a common source of disability for patients with Parkinson's disease. Evidence suggests that motor complications are associated with non-physiological, pulsatile stimulation of dopamine receptors. In healthy brains, dopamine neurons fire continuously, striatal dopamine concentrations are relatively constant, and there is continuous activation of dopamine receptors. In the dopamine-depleted state, standard levodopa therapy does not normalise the basal ganglia. Rather, levodopa or other short-acting dopaminergic drugs induce molecular changes and altered neuronal firing patterns in basal ganglia neurons leading to motor complications. The concept of continuous dopaminergic stimulation proposes that continuous delivery of a dopaminergic drug will prevent pulsatile stimulation and avoid motor complications. In monkeys treated with MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and patients with Parkinson's disease, long-acting or continuous infusion of a dopaminergic drug reduces the risk of motor complications. The current challenge is to develop a long-acting oral formulation of levodopa that provides clinical benefits but avoids 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

16857573

Citation

Olanow, C Warren, et al. "Continuous Dopamine-receptor Treatment of Parkinson's Disease: Scientific Rationale and Clinical Implications." The Lancet. Neurology, vol. 5, no. 8, 2006, pp. 677-87.
Olanow CW, Obeso JA, Stocchi F. Continuous dopamine-receptor treatment of Parkinson's disease: scientific rationale and clinical implications. Lancet Neurol. 2006;5(8):677-87.
Olanow, C. W., Obeso, J. A., & Stocchi, F. (2006). Continuous dopamine-receptor treatment of Parkinson's disease: scientific rationale and clinical implications. The Lancet. Neurology, 5(8), 677-87.
Olanow CW, Obeso JA, Stocchi F. Continuous Dopamine-receptor Treatment of Parkinson's Disease: Scientific Rationale and Clinical Implications. Lancet Neurol. 2006;5(8):677-87. PubMed PMID: 16857573.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Continuous dopamine-receptor treatment of Parkinson's disease: scientific rationale and clinical implications. AU - Olanow,C Warren, AU - Obeso,Jose A, AU - Stocchi,Fabrizio, PY - 2006/7/22/pubmed PY - 2006/9/6/medline PY - 2006/7/22/entrez SP - 677 EP - 87 JF - The Lancet. Neurology JO - Lancet Neurol VL - 5 IS - 8 N2 - Levodopa-induced motor complications are a common source of disability for patients with Parkinson's disease. Evidence suggests that motor complications are associated with non-physiological, pulsatile stimulation of dopamine receptors. In healthy brains, dopamine neurons fire continuously, striatal dopamine concentrations are relatively constant, and there is continuous activation of dopamine receptors. In the dopamine-depleted state, standard levodopa therapy does not normalise the basal ganglia. Rather, levodopa or other short-acting dopaminergic drugs induce molecular changes and altered neuronal firing patterns in basal ganglia neurons leading to motor complications. The concept of continuous dopaminergic stimulation proposes that continuous delivery of a dopaminergic drug will prevent pulsatile stimulation and avoid motor complications. In monkeys treated with MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and patients with Parkinson's disease, long-acting or continuous infusion of a dopaminergic drug reduces the risk of motor complications. The current challenge is to develop a long-acting oral formulation of levodopa that provides clinical benefits but avoids motor complications. SN - 1474-4422 UR - https://www.unboundmedicine.com/medline/citation/16857573/Continuous_dopamine_receptor_treatment_of_Parkinson's_disease:_scientific_rationale_and_clinical_implications_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1474-4422(06)70521-X DB - PRIME DP - Unbound Medicine ER -