Selegiline !

An irreversible MAO-B inhibitor for Parkinson disease. It forms amphetamine metabolites and has serious interactions with meperidine and antidepressants.

Updated 2026-11-01

Class: MAO-B inhibitors
Enzyme: Monoamine oxidase B (MAO-B)
ATC code: N04BD01

Also called: L-deprenyl

Monoamine oxidase B (MAO-B)Selegiline

The figure shows deprenyl (selegiline) in human MAO-B, next to the FAD cofactor it binds covalently.

Target in 3D: Monoamine oxidase B (MAO-B). PDB structure 2BYB (RCSB PDB, public domain). View the structure at RCSB PDB

Mechanism of action

Selegiline is a «suicide» substrate of MAO-B: the enzyme converts it to a reactive form that binds its flavin cofactor irreversibly. Less dopamine is broken down in the striatum. Selectivity for MAO-B depends on dose and is lost at higher doses. It is metabolized to L-amphetamine and L-methamphetamine.

MAO-B activates selegiline, which binds its FAD for good
Striatal dopamine is broken down more slowly
Levodopa effects last longer

Pharmacokinetics

Metabolism: Extensive first-pass metabolism to desmethylselegiline, L-amphetamine and L-methamphetamine
Onset and duration: Enzyme inhibition lasts until new MAO-B is made, beyond the drug's presence in blood

Indications

Parkinson disease, as an adjunct to levodopa + carbidopa when the response is fading, or early in the disease Parkinson disease →

Adverse effects

Common

Nausea, dizziness, dry mouth
Insomnia and anxiety (amphetamine metabolites)
More dyskinesia and hallucinations when added to levodopa
Orthostatic hypotension

Contraindications

Meperidine (often extended to other opioids)
Hypersensitivity to selegiline

Key interactions

Meperidine, tramadol, methadone: Serotonin toxicity: agitation, rigidity, hyperthermia
SSRIs, SNRIs, tricyclic antidepressants: Serotonin syndrome and severe CNS toxicity
Ephedrine and other sympathomimetics (cough and cold products): Hypertensive crisis
Levodopa + carbidopa: More dyskinesia; severe orthostatic hypotension reported

What is monitored

Blood pressure (high and orthostatic)
Sleep, anxiety and hallucinations
All new medicines, including over-the-counter cold remedies and opioids

Administration and safety

Doses are given with breakfast and lunch, not in the evening
Oral tablets, capsules, orally disintegrating tablets and a skin patch are different products
A drug-free gap is needed before starting interacting drugs

Nursing care

Flag the record: no meperidine; check every new opioid or antidepressant
Teach to avoid decongestants and very tyramine-rich foods
Check blood pressure and ask about sleep
Watch for agitation, fever, sweating or muscle rigidity

Pregnancy and breastfeeding

Human data are lacking; animal studies did not show malformations.

Test yourself

Think of the answer, then tap the question to see it.

Which metabolites of selegiline explain its insomnia and anxiety?

L-amphetamine and L-methamphetamine.

Which opioid is contraindicated with selegiline?

Meperidine (stupor, rigidity, agitation, hyperthermia); the warning is often extended to other opioids.

What happens to MAO-B selectivity at higher selegiline doses?

It is lost: MAO-A is also inhibited, so tyramine and pressor reactions become possible.

Add to my cards (3)

Parkinson disease

← Back to the class: MAO-B inhibitors

Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: DailyMed - SELEGILINE HYDROCHLORIDE tablet (DailyMed (U.S. National Library of Medicine), 2026); Selegiline: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2022); Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 21 (McGraw Hill, 2023).

Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake

Representative model, for educational purposes only.