Effects of 3-O-Methyldopa, L-3,4-Dihydroxyphenylalanine Metabolite, on Locomotor Activity and Dopamine Turnover in Rats
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概要
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It has been well known that 3-O-methyldopa (3-OMD) is a metabolite of L-3,4-dihydroxyphenylalanine (L-DOPA) formed by catechol O-methyltransferase (COMT), and 3-OMD blood level often reaches higher than physiological level in Parkinson’s disease (PD) patients receiving long term L-DOPA therapy. However, the physiological role of 3-OMD has not been well understood. Therefore, in order to clarify the effects of 3-OMD on physiological function, we examined the behavioral alteration in rats based on locomotor activity, and measured dopamine (DA) and its metabolites levels in rats at the same time after 3-OMD subchronic administration. The study results showed that repeated administrations of 3-OMD increased its blood and the striatum tissue levels in those rats, and decreased locomotor activity in a dose dependent manner. Although 3-OMD subchronic administration showed no significant change in DA level in the striatum, DA metabolite levels, such as 3,4-dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3-MT), and homovanillic acid (HVA) were significantly decreased. After 3-OMD washout period (7 d), locomotor activity and DA turnover in those rats returned to normal levels. Furthermore, locomotor activity and DA turnover decreased by 3-OMD administration were recovered to normal level by acute L-DOPA administration. These results suggested that 3-OMD affect to locomotor activity via DA neuron system. In conclusion, 3-OMD itself may have a disadvantage in PD patients receiving L-DOPA therapy.
著者
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Kimura Yasuhiro
Department Of Biophysics Kanazawa University School Of Medicine
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Kihira Kenji
Division of Clinical Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Hiroshima University
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Taogoshi Takanori
Division of Clinical Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Hiroshima University
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Onzawa Yoritaka
Division of Clinical Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Hiroshima University
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Uzuhashi Kengo
Division of Clinical Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Hiroshima University
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Shirasuna Megumi
Division of Clinical Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Hiroshima University
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Hirosawa Tasuku
Division of Clinical Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Hiroshima University
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KIMURA Yasuhiro
Department of Applied Chemistry, Faculty of Engineering, Kanagawa University
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