General properties and clinical possibilities of new selective inhibitors of catechol O-methyltransferase

Gen Pharmacol. 1994 Sep;25(5):813-24. doi: 10.1016/0306-3623(94)90082-5.


1. The structure of catechol O-methyltransferase (COMT) has been recently characterized and a series of new and selective COMT inhibitors developed. 2. Entacapone, nitecapone and tolcapone are nitrocatechol-type potent COMT inhibitors in vitro (Ki in nanomolar range). They are also very selective for COMT and active in vivo even after oral administration. CGP 28014 is a pyridine derivative that is active only in vivo. 3. In animal studies, these compounds inhibit effectively the O-methylation of L-dopa, thus improving its bioavailability and brain penetration and potentiating its behavioural effects. 4. Entacapone and nitecapone have mainly a peripheral effect whereas tolcapone and CGP 28014 also inhibit O-methylation in the brain. 5. In man, entacapone, nitecapone and tolcapone all inhibit dose dependently the COMT activity in erythrocytes. These COMT inhibitors also decrease the amount of COMT dependent metabolites of adrenaline and noradrenaline in plasma. 6. In human volunteers, entacapone, tolcapone and CGP 28014 improve the bioavailability of L-dopa and inhibit the formation of 3-O-methyldopa. 7. In the first clinical studies in patients with Parkinson's disease, both entacapone and tolcapone potentiate and prolong the therapeutic effect of L-dopa.

Publication types

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

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Benzophenones / pharmacology
  • Catechol O-Methyltransferase Inhibitors*
  • Catecholamines / metabolism
  • Catechols / pharmacokinetics
  • Catechols / pharmacology
  • Dihydroxyphenylalanine / analogs & derivatives
  • Dihydroxyphenylalanine / pharmacokinetics
  • Humans
  • Levodopa / metabolism
  • Microdialysis
  • Nitriles
  • Nitrophenols
  • Pentanones / pharmacology
  • Tolcapone
  • Tomography, Emission-Computed


  • Benzophenones
  • Catechol O-Methyltransferase Inhibitors
  • Catecholamines
  • Catechols
  • Nitriles
  • Nitrophenols
  • Pentanones
  • fluorodopa F 18
  • Levodopa
  • entacapone
  • Dihydroxyphenylalanine
  • nitecapone
  • Tolcapone