Pramipexole has ameliorating effects on levodopa-induced abnormal dopamine turnover in parkinsonian striatum and quenching effects on dopamine-semiquinone generated in vitro

Masato Asanuma, Ikuko Miyazaki, Francisco J. Diaz-Corrales, Masako Shimizu, Ken Ichi Tanaka, Norio Ogawa

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Objectives and methods: To clarify the effects of a non-ergot dopamine agonist pramipexole on levodopa-induced abnormal dopamine metabolism in the parkinsonian model, we examined striatal changes in dopamine and its metabolites after repeated administration of pramipexole and/or levodopa using 6-hydroxydopamine-lesioned hemi-parkinsonian mice. Moreover, the effects of pramipexole on dopamine-semiquinones were also accessed using an in vitro dopamine-semiquinone generating system to elucidate its neuroprotective property against dopamine quinone-induced neurotoxicity that appears as dopamine neuron-specific oxidative stress. Results: Combined administration of pramipexole (0.5 or 1 mg/kg/day, 7 days) selectively suppressed the levodopa-induced (50 mg/kg/day) increase of striatal dopamine turnover in the parkinsonian side, but not in the non-lesioned side. In addition to the antioxidant properties previously reported, it was clarified that pramipexole scavenged dopamine-semiquinones generated in a dose-dependent manner either in simultaneous incubation or post-incubation. Discussion: The neurotoxicity of dopamine quinones that appear as dopaminergic neuron-specific oxidative stress has recently been known to play a role in the pathogenesis of Parkinson's disease and neurotoxin-induced parkinsonism. Therefore, the present results revealed that pramipexole possesses neuroprotective effects against abnormal dopamine metabolism in excessively levodopa-administered parkinsonian brains and against cytotoxic dopamine quinones generated from excess dopamine, preventing consequently dopaminergic neuronal damage induced by excess dopamine or levodopa.

Original languageEnglish
Pages (from-to)533-539
Number of pages7
JournalNeurological Research
Volume27
Issue number5
DOIs
Publication statusPublished - Jul 2005

Keywords

  • Dopamine quinone
  • Dopamine turnover
  • Levodopa
  • Parkinson's disease
  • Pramipexole

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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