Pharmacology · Antiparkinson Drugs
Enzyme Inhibitors
Monoamine oxidase B inhibitors and catechol-O-methyltransferase inhibitors
- MAO-B inhibitors (selegiline, rasagiline, safinamide) reduce dopamine breakdown in the striatum by blocking the primary catabolic enzyme — they extend levodopa effect and provide modest symptomatic benefit as monotherapy in early disease.
- Selegiline is metabolized to amphetamine and methamphetamine, causing insomnia and anxiety — it must be taken in the morning and at midday only; rasagiline produces an inert metabolite and is the cleaner, preferred agent.
- All MAO-B inhibitors carry an absolute contraindication to meperidine (hyperthermia and rigidity risk) and a caution against serotonergic drugs; tyramine risk is lower than with nonselective MAO inhibitors but patients should still be counseled.
- COMT inhibitors (entacapone, tolcapone, opicapone) block the peripheral conversion of levodopa to 3-O-methyldopa, extending plasma levodopa half-life and smoothing motor fluctuations — they are always used as adjuncts with levodopa, never as monotherapy.
- Tolcapone carries a black box warning for potentially fatal hepatic failure — it is reserved for patients who have failed entacapone or opicapone; orange urine discoloration is a harmless class effect of all COMT 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
MAO-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 MAO-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 COMT 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.