Effects of 3-O-methyldopa, L-3,4-dihydroxyphenylalanine metabolite, on locomotor activity and dopamine turnover in rats

Biol Pharm Bull. 2012;35(8):1244-8. doi: 10.1248/bpb.b110714.

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.

MeSH terms

  • Animals
  • Antiparkinson Agents / adverse effects
  • Antiparkinson Agents / metabolism
  • Antiparkinson Agents / pharmacology*
  • Brain / drug effects*
  • Brain / metabolism
  • Dopamine / analogs & derivatives
  • Dopamine / metabolism*
  • Dose-Response Relationship, Drug
  • Levodopa / adverse effects*
  • Levodopa / metabolism
  • Levodopa / therapeutic use
  • Male
  • Motor Activity / drug effects*
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / metabolism
  • Rats
  • Rats, Wistar
  • Tyrosine / adverse effects
  • Tyrosine / analogs & derivatives*
  • Tyrosine / metabolism

Substances

  • Antiparkinson Agents
  • Tyrosine
  • Levodopa
  • 3-methoxytyrosine
  • Dopamine