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The dopamine transporter: Importance in Parkinson's disease
Author(s) -
Nutt John G.,
Carter Julie H.,
Sexton Gary J.
Publication year - 2004
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.20089
Subject(s) - levodopa , dopamine transporter , dyskinesia , parkinsonism , dopamine , methylphenidate , parkinson's disease , dopamine plasma membrane transport proteins , medicine , pharmacology , anesthesia , psychology , dopaminergic , disease , attention deficit hyperactivity disorder , psychiatry
The dopamine transporter (DAT) may be the single most important determinant of extracellular dopamine concentrations. The importance of DAT in Parkinson's disease (PD) in which DAT may be reduced by 50 to 70% is unclear. We have examined the effects of methylphenidate (MPD), an inhibitor of DAT, administered alone or with levodopa, on parkinsonism measured with tapping and walking speeds, dyskinesia, subjective effects, and vital signs. MPD in oral doses of up to 0.4mg/kg was well tolerated. Administered alone, MPD produced no objective improvement of parkinsonism. MPD, 0.4mg/kg orally, coadministered with 2‐hour levodopa infusions at 0.5 or 1.0mg/kg/hr increased the percentage of patients responding to the 0.5mg/kg/hr dose and prolonged the response to levodopa infusions as measured by tapping and walking speeds. Dyskinesia was prolonged in proportion to the increase in antiparkinson actions but severity was not increased. MPD decreased the hypotensive response to levodopa. In conclusion, MPD appeared to have no effect given alone but potentiated the effects of levodopa, particularly doses at threshold for clinical effects. These observations indicate that the residual DAT is functional in PD and is a potential target for symptomatic therapy of PD.