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

Asanuma M, Miyazaki I, Diaz-Corrales FJ, Shimizu M, Tanaka K, Ogawa N

Department of Brain Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. asachan@cc.okayama-u.ac.jp

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.

Published 27 June 2005 in Neurol Res, 27(5): 533-9.
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