Noradrenaline in Parkinson's Disease: From Disease Progression to Current Therapeutics

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Abstract:

The loss of the neurotransmitter noradrenaline occurs constantly in Parkinson's disease. This is supposed to worsen disease progression, either by increasing the vulnerability of dopamine-containing neurons or by reducing the recovery once they are damaged. Novel data also show that the loss of noradrenergic innervation facilitates the onset of dyskinesia occurring in Parkinsonian patients during dopamine replacement therapy.

In the first part of the manuscript we review the evidence showing the loss of the noradrenergic system as an early event in the natural history of Parkinsonism. This evidence is discussed in light of novel reports showing the deleterious effects produced by the noradrenergic deficit on the survival of nigral dopamine neurons. In particular, we analyze the biochemical and morphological changes produced in the nigrostriatal system by the loss of endogenous noradrenaline. In a dedicated paragraph we specifically evaluate the cross affinity between dopamine and noradrenaline systems. In fact, this is critical during dopamine/noradrenaline replacement therapy in Parkinson's disease.

In the last part, we overview novel therapeutic approaches aimed at restoring the activation of noradrenaline receptors to reduce the dyskinesia occurring in the treatment of Parkinson's disease.

Keywords: D1 receptors; DA agonists; L-DOPA; Neurodegeneration; alpha receptors; dyskinesia; locus coeruleus

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986707781745550

Affiliations: Department of Human Morphology and Applied Biology, University of Pisa, Via Roma, 55, 56126, Pisa,Italy.

Publication date: September 1, 2007

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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