ApprovedFDA approved

Selegiline

Selective MAO-B inhibitor, Parkinson`s + depression, FDA-approved.

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WHAT IS SELEGILINE?

Detailed overview

Selegiline (L-deprenyl) is a development of Hungarian Prof. József Knoll (1960s), a selective and irreversible MAO-B inhibitor. FDA-approved for Parkinson`s disease (oral, Eldepryl/Zelapar) and major depression (transdermal Emsam patch). At low doses (<10 mg/day) the selectivity is preserved; higher doses also inhibit MAO-A → tyramine-reaction risk rises. **The Emsam transdermal patch advantage**: bypasses gut MAO, so the 6 mg/24h dose is safe without a tyramine-restricted diet (FDA approval for MDD on this basis). The active metabolites (l-amphetamine + l-methamphetamine) are pharmacologically present, but at low doses cognitive clarity is preserved. **Antiapoptotic + NGF-like neuroprotective effect** on nigrostriatal dopaminergic neurons – Knoll`s original hypothesis. The DATATOP clinical trial showed slowing of Parkinson`s progression.

Mechanism

Selective, irreversible MAO-B

Half-life

~10 h (active metabolites longer)

Legal status

FDA + EU Rx

Safety

Side effects, stop signs, contraindications

Side effects · 6

  • Insomnia and disturbed sleep from the l-amphetamine/l-methamphetamine metabolites, hence morning dosing
  • Nausea, gastrointestinal upset, dry mouth
  • Orthostatic hypotension, dizziness, lightheadedness (especially at Parkinson-level doses)
  • Headache
  • Vivid dreams, less commonly hallucinations or confusion (in the elderly, at higher doses)
  • With the transdermal patch (Emsam), redness and itching at the application site

Contraindications · 6

  • Concurrent SSRIs/SNRIs/tricyclics, tramadol, meperidine, dextromethorphan: serotonin syndrome risk, avoid
  • At higher doses (>10 mg/day oral) MAO-B selectivity is lost: hypertensive crisis risk with tyramine-rich foods
  • Sympathomimetics, stimulants, ephedrine/pseudoephedrine concurrently: hypertensive reaction, do not stack
  • Must not be combined with other MAO inhibitors or linezolid
  • Not recommended in pregnancy and breastfeeding (insufficient safety data, amphetamine metabolites)
  • Only under specialist supervision; prescription-only, not suitable for self-medication

Related Nootropics

Same therapeutic category

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MolekulaX Editorial Team·Source-verified · PubMed · FDA · EMA
Updated: June 19, 2026

The information here is strictly for educational and scientific purposes. It does not replace medical advice or clinical consultation, and it does not encourage illegal substance or pharmaceutical use. Data is sourced. When in doubt, consult your doctor.