1. Effects of 3-O-methyldopa, L-3,4-dihydroxyphenylalanine metabolite, on locomotor activity and dopamine turnover in rats.
- Author
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Onzawa Y, Kimura Y, Uzuhashi K, Shirasuna M, Hirosawa T, Taogoshi T, and Kihira K
- Subjects
- Animals, Antiparkinson Agents adverse effects, Antiparkinson Agents metabolism, Brain metabolism, Dopamine analogs & derivatives, Dose-Response Relationship, Drug, Levodopa metabolism, Levodopa therapeutic use, Male, Parkinson Disease metabolism, Rats, Rats, Wistar, Tyrosine adverse effects, Tyrosine metabolism, Antiparkinson Agents pharmacology, Brain drug effects, Dopamine metabolism, Levodopa adverse effects, Motor Activity drug effects, Parkinson Disease drug therapy, Tyrosine analogs & derivatives
- Abstract
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.
- Published
- 2012
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