Chapter 18  ·  Module 5
Enzyme Inhibitors
Monoamine oxidase B inhibitors and catechol-O-methyltransferase inhibitors
Monoamine Oxidase B Inhibitors
Selegiline Rasagiline Safinamide
Reversibility Irreversible Irreversible Reversible
Metabolite Amphetamine, methamphetamine Aminoindan (inert) Inert metabolites
Key concern Insomnia, anxiety — take morning and midday only Cleaner profile — preferred agent Adjunct with levodopa only; also blocks sodium channels
Class Effect
Monoamine Oxidase B Inhibitor Interactions
  • Meperidine absolutely contraindicated — hyperthermia, rigidity
  • Serotonergic drugs — serotonin syndrome risk
  • Tyramine risk lower than nonselective inhibitors but counsel patients
Clinical Use
When Monoamine Oxidase B Inhibitors Are Used
  • Early mild disease — monotherapy for modest symptomatic benefit
  • Adjunct with levodopa — reduces wearing-off
  • Effect more modest than dopamine agonists or catechol-O-methyltransferase inhibitors
Catechol-O-Methyltransferase Inhibitors
Entacapone Tolcapone Opicapone
Site of action Peripheral only Peripheral and central Peripheral only
Dosing With each levodopa dose Three times daily Once daily at bedtime
Hepatotoxicity No Yes — black box warning No
Key note First choice — excellent safety Reserved for entacapone failures Convenient once-daily dosing
Black Box Warning — Tolcapone
Tolcapone carries a black box warning for potentially fatal hepatic failure. Liver function must be monitored regularly. Use only when entacapone or opicapone have failed. Orange urine discoloration is a harmless class effect of all catechol-O-methyltransferase inhibitors.