BIA 3-202, a novel catechol-O-methyltransferase inhibitor, reduces the peripheral O-methylation of L-DOPA and enhances its availability to the brain

Pharmacology. 2003 May;68(1):29-37. doi: 10.1159/000068730.


The present study aims at determining the effects of the catechol-O-methyltransferase (COMT) inhibitor BIA 3-202 [1-(3,4-dihydroxy-5-nitrophenyl)-2-phenyl-ethanone] upon levels of L-3,4-dihydroxyphenylalanine (L-DOPA) and metabolites in peripheral circulation (jugular vein), whole brain, and striatal microdialysates in rats orally treated with L-DOPA plus benserazide. A low dose (3 mg/kg) of BIA 3-202 was relatively selective to inhibit liver COMT, being devoid of major significant inhibitory effects upon brain COMT. By contrast, a high dose (30 mg/kg) of BIA 3-202 markedly inhibited liver and brain COMT. BIA 3-202 (3 and 30 mg/kg) reduced the L-DOPA-induced rise of 3-O-methyl-L-DOPA in the peripheral circulation (jugular vein), brain tissue, and striatal dialysate, but failed to increase the levels of dopamine in striatal dialysates despite the increase in dopamine brain levels. However, the changes in brain levels of L-DOPA, 3-O-methyl-L-DOPA, and dopamine and in striatal dialysate levels of L-DOPA and 3-O-methyl-L-DOPA, obtained with 3 mg/kg BIA 3-202, were not different from those obtained with 30 mg/kg BIA 3-202. In conclusion, inhibition of peripheral COMT by BIA 3-202 may suffice to improve the availability of L-DOPA to the brain.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetophenones / pharmacology*
  • Animals
  • Antiparkinson Agents / metabolism
  • Antiparkinson Agents / pharmacokinetics*
  • Biological Availability
  • Brain / drug effects*
  • Brain / metabolism
  • Catechol O-Methyltransferase / metabolism
  • Catechol O-Methyltransferase Inhibitors*
  • Dopamine / metabolism
  • Dose-Response Relationship, Drug
  • Levodopa / metabolism
  • Levodopa / pharmacokinetics*
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Methylation
  • Microdialysis
  • Rats
  • Rats, Wistar


  • Acetophenones
  • Antiparkinson Agents
  • Catechol O-Methyltransferase Inhibitors
  • Levodopa
  • Catechol O-Methyltransferase
  • nebicapone
  • Dopamine