Continuous dopamine-receptor treatment of Parkinson's disease: scientific rationale and clinical implications

C. Warren Olanow, Jose A. Obeso, Fabrizio Stocchi

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)677-687
Number of pages11
JournalThe Lancet Neurology
Volume5
Issue number8
DOIs
Publication statusPublished - Aug 2006

ASJC Scopus subject areas

  • Clinical Neurology

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