Pramipexole has ameliorating effects on levodopa-induced abnormal dopamine turnover in parkinsonian striatum and quenching effects on dopamine-semiquinone generated in vitro
Authors: Asanuma, Masato1; Miyazaki, Ikuko1; Diaz-Corrales, Francisco J.1; Shimizu, Masako1; Tanaka, Ken-ichi2; Ogawa, Norio1
Source: Neurological Research, Volume 27, Number 5, July 2005 , pp. 533-539(7)
Publisher: Maney Publishing
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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.Keywords: DOPAMINE QUINONE; DOPAMINE TURNOVER; LEVODOPA; PARKINSON'S DISEASE; PRAMIPEXOLE
Document Type: Research article
DOI: 10.1179/016164105X22093
Affiliations: 1: Department of Brain Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan 2: Department of Clinical Pharmacy, Shujitsu University School of Pharmacy, Okayama, Japan
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