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Beating a dead horse

Dopamine and Parkinson disease

From the Department of Neurology, Mayo Clinic, Rochester, MN.

Address correspondence and reprint requests to Dr. J. Eric Ahlskog, Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905

Our collective thinking about Parkinson disease (PD) has been heavily influenced by the dramatic response to dopamine replacement therapy. For progress to continue, however, we need to take a broad view of this disorder, which includes recognition of the following. First, substantial evidence now indicates that dopamine oxidation is unlikely to substantially contribute to the pathogenesis of PD. Second, levodopa therapy is not associated with neurotoxicity. Third, the first neurons affected in PD are nondopaminergic; the substantia nigra and other dopaminergic nuclei are affected only later in the course. Thus, PD is much more than degeneration of the dopaminergic nigrostriatal system. Fourth, in the current era, most of the disability of advancing PD is from involvement of nondopaminergic systems, including levodopa-refractory motor symptoms, dementia, and dysautonomia. Motor complications associated with levodopa therapy can be problematic, but they can be controlled in most, using available medications and deep brain stimulation surgery. We have reached the point of diminishing therapeutic returns with drugs acting on dopamine systems; more dopaminergic medications will provide only modest incremental benefit over current therapies. Finally, the benefits from transplantation surgeries aimed at restoring dopaminergic neurotransmission will be limited because later-stage PD disability comes from nondopaminergic substrates.

GLOSSARY: CDS = continuous dopaminergic stimulation; DBS = deep brain stimulation; GABAergic = -aminobutyric acid–mediated; MPTP = 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; PD = Parkinson disease; STN = subthalamic nucleus; UPDRS = Unified Parkinson’s Disease Rating Scale.

eahlskog{at}mayo.edu

Disclosure: The author reports no conflicts of interest.

Received February 4, 2007. Accepted in final form April 17, 2007.

This article has been cited by other articles:

				W. J. Burke BEATING A DEAD HORSE: DOPAMINE AND PARKINSON DISEASE Neurology, May 27, 2008; 70(22): 2087 - 2087. [Full Text] [PDF]

				C. Marras and A. Lang Invited Article: Changing concepts in Parkinson disease: Moving beyond the Decade of the Brain Neurology, May 20, 2008; 70(21): 1996 - 2003. [Abstract] [Full Text] [PDF]

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