1. Neurology. 2007 Oct 23;69(17):1701-11.

Beating a dead horse: dopamine and Parkinson disease.

Ahlskog JE.

Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905,
USA. eahlskog@mayo.edu

Comment in:
Neurology. 2008 May 27;70(22):2087.
Neurology. 2008 Nov 11;71(20):1651; author reply 1651-2.

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. Scale.

PMID: 17954785 [PubMed - indexed for MEDLINE]