title: Effects of 3-O-methyldopa, L-3,4-dihydroxyphenylalanine metabolite, on locomotor activity and dopamine turnover in rats.
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.
authors.affiliation: Division of Clinical Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Hiroshima University, Japan. doco1551bad@yahoo.co.jp
authors.forename: Yoritaka
authors.initials: Y
authors.lastname: Onzawa
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kimura
authors.forename: Kengo
authors.initials: K
authors.lastname: Uzuhashi
authors.forename: Megumi
authors.initials: M
authors.lastname: Shirasuna
authors.forename: Tasuku
authors.initials: T
authors.lastname: Hirosawa
authors.forename: Takanori
authors.initials: T
authors.lastname: Taogoshi
authors.forename: Kenji
authors.initials: K
authors.lastname: Kihira
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000031:analogs & derivatives / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007980:Levodopa / Q000009:adverse effects* / Q000378:metabolism / Q000627:therapeutic use; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014443:Tyrosine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D000978:Antiparkinson Agents; D014443:Tyrosine; D007980:Levodopa; C008404:3-methoxytyrosine; D004298:Dopamine