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The “Parkinsonian Heart”: From Novel Vistas to Advanced Therapeutic Approaches in Parkinson's Disease

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Abstract:

The present manuscript reviews novel data on the progressive involvement of different regions of the central nervous system as well as peripheral nerves in Parkinson's disease. Most of these regions are involved in the regulation of the autonomic nervous system, and their damage is concomitant with the specific loss of sympathetic cardiac axon terminals. This causes a cardiovascular dysfunction, which occurs solely in Parkinsonian patients. In order to specify the peculiarity of this cardiovascular alteration we coined the term “Parkinsonian Heart”. This is characterized by a severe loss of the physiological noradrenergic innervation and a slight impairment of central autonomic control and it is often characterized by drug-induced morpho-functional alterations. In fact, the current dopamine substitution therapy could make worse such an already abnormal heart. For instance, structure-activity studies on dopamine substitutive drugs report that dopamine agonists belonging to the class of ergot derivatives may produce, with a high frequency, valvular fibrosis in Parkinsonian patients. These effects recently became a major issue and led to consider all ergot dopamine agonists as dangerous for the treatment of Parkinson's disease. In the present review we re-describe the effects of dopamine agonist within the specific context of the Parkinsonian heart. In line with this, additional factors need to be considered: 1- The lack of noradrenergic innervation which might play a significant role in the fibrogenic mechanism. 2- The ergot structure per se, which is not sufficient, but it is rather the ability to act as agonist at 5HT2B or alpha-noradrenergic receptors to determine the fibrotic reaction. Therefore, we suggest that binding to these receptor subtypes, joined with the lack of endogenous noradrenergic innervation, might synergize to produce the cardiac fibrosis.

Keywords: Cardiac fibrosis; Dopamine agonists; Ergot derivatives; Multiple system atrophy; Noradrenaline; Orthostatic hypotension; Parkinson's disease; Sympathetic nervous system

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986707782023631

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

Publication date: October 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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