The dopamine transporter: Importance in Parkinson's disease

John Nutt, Julie Carter, Gary J. Sexton

Research output: Contribution to journalArticle

72 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)766-773
Number of pages8
JournalAnnals of Neurology
Volume55
Issue number6
DOIs
Publication statusPublished - Jun 2004

    Fingerprint

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this