Catechol-O-methyltransferase inhibitor

[1] Entacapone and opicapone are peripherally selective inhibitors, unable to cross the blood–brain barrier (BBB), and hence do not inhibit COMT in the brain.

[3] Instead, the drug seems to exert most of its clinical efficacy in this condition through inhibition of peripheral COMT and is dependent on concomitant use of levodopa.

[8] Tolcapone, which acts centrally in addition to peripherally, has shown antidepressant-like effects in animal models of depression.

[10] However, these antidepressant-like effects may only occur with combination treatment of tolcapone with levodopa and an aromatic L-amino acid decarboxylase inhibitor.

[11] There may be compensatory activation of the monoamine oxidase dopamine-metabolizing pathway with brain COMT inhibition.

Metabolism of levodopa by catechol- O -methyltransferase (COMT) and aromatic L-amino acid decarboxylase (AADC). COMT inhibitors prevent the conversion of levodopa to 3- O -methyldopa.