Effects of three types of catechol O-methylation inhibitors on L-3,4-dihydroxyphenylalanine-induced circling behaviour in rats

Eur J Pharmacol. 1993 Nov 30;250(1):77-84. doi: 10.1016/0014-2999(93)90623-p.

Abstract

The effects of three new, selective inhibitors of catechol O-methylation were compared regarding their potentiation of L-3,4-dihydroxyphenylalanine (L-dopa)/carbidopa-induced contralateral circling behaviour in male rats. Some studies were also done with amphetamine, which causes ipsilateral turning. A peripherally acting compound, entacapone, a peripherally and centrally acting compound, tolcapone, and an atypical compound, CGP 28014 (3, 10 or 30 mg/kg) increased the effect of L-dopa/carbidopa (2/30 or 5/30 mg/kg) on contralateral circling by 2.0-6.1-fold. Addition of clorgyline (3 mg/kg) did not increase, but rather decreased, the entacapone (3 mg/kg) and L-dopa/carbidopa (2/30 or 5/30 mg/kg)-induced peak circling. Amphetamine (2.5 mg/kg)-induced ipsilateral circling behaviour was not affected by tolcapone (30 mg/kg). We conclude that L-dopa-induced circling behaviour is enhanced and prolonged by all types of catechol O-methyltransferase inhibitors regardless of their brain penetration. The results suggest that catechol O-methylation inhibitors may be beneficial as L-dopa adjuncts in the treatment of patients with Parkinson's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amidines / pharmacology*
  • Amphetamine / pharmacology
  • Animals
  • Behavior, Animal / drug effects*
  • Benzophenones / pharmacology*
  • Carbidopa / pharmacology
  • Catechol O-Methyltransferase Inhibitors*
  • Catechols / pharmacology*
  • Clorgyline / pharmacology
  • Drug Interactions
  • Drug Synergism
  • Levodopa / pharmacology*
  • Male
  • Methylation
  • Nitriles
  • Nitrophenols
  • Pyridones / pharmacology*
  • Rats
  • Rats, Wistar
  • Tolcapone

Substances

  • Amidines
  • Benzophenones
  • Catechol O-Methyltransferase Inhibitors
  • Catechols
  • Nitriles
  • Nitrophenols
  • Pyridones
  • N-(2-pyridone-6-yl)-N',N'-di-n-propylformamidine
  • Levodopa
  • entacapone
  • Tolcapone
  • Amphetamine
  • Clorgyline
  • Carbidopa