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Selegiline (l-deprenyl)
An MAO-B-inhibitor drug approved for Parkinson's disease and depression, long studied as a longevity/neuroprotection agent. It extended lifespan in some rodent studies (with mixed results across labs), but there is no human longevity evidence, and it carries MAO-inhibitor interaction risks. A prescription drug used off-label, not a supplement.
Prescription medication — not a dietary supplement
Selegiline is a prescription (or investigational) drug, not a supplement. It is included here for reference because people research and discuss it (often used off-label) — not as a recommendation. Take it only under a qualified clinician's supervision and only as prescribed; do not source it from grey-market vendors, where identity, purity, and dosing are unverified. The evidence below reflects its clinical trials.
What the evidence says
Most Selegiline studies are mechanism or observational rather than RCTs that measure a clinical effect — keep findings provisional.
Most evidence is from high-quality meta-analyses and randomised trials published 1978–2026 with a typical study size of 903 participants.
Based on 172 studies · 9 meta-analyses · 153 RCTs · 4,723 total participants
Confidence
High confidenceBy outcome
Selegiline has a credible neuroprotective/antioxidant mechanism, and a 2025 meta-analysis of 22 experiments concluded it reproducibly extends lifespan across mammalian species (upgrading the earlier mixed individual-study picture); but there is still no human longevity evidence and it carries MAO-inhibitor interaction risks.
164 rigorous studies
156 randomized trials · 6 meta-analyses · 2 systematic reviews
Our evidence rating for Selegiline is accountable to this entire body of rigorous research indexed in PubMed — not a hand-picked subset.
PubMed · as of Jul 2026
1 trial ongoing or recruiting · 27 completed on ClinicalTrials.gov
7 of the completed trials have posted results
Registered trials show research momentum for Selegiline, not proof of effect — a registration is a plan, and posted results are sponsor-reported, not peer-reviewed. They are never counted toward the evidence rating above.
Browse these trials on ClinicalTrials.govClinicalTrials.gov · as of Aug 2026
Selegiline (l-deprenyl) is a selective, irreversible inhibitor of monoamine oxidase B (MAO-B) — the enzyme that degrades dopamine in the brain.
It is FDA-approved for Parkinson's disease (oral) and major depression (the Emsam transdermal patch), and it has been one of the longest-standing candidates in 'anti-aging' pharmacology.
Its longevity rationale is several-fold: by inhibiting MAO-B it preserves dopamine and reduces the hydrogen-peroxide generated by dopamine breakdown, and it independently upregulates antioxidant enzymes (superoxide dismutase, catalase) and shows neuroprotective, anti-apoptotic effects in neuronal models.
The historical excitement came from animal lifespan studies — most famously in rats and in aged beagle dogs, where low-dose deprenyl improved survival, cognition, and motor function in several reports.
The honest picture is more tempered: the rodent lifespan results are genuinely mixed across laboratories (some found extension, particularly in females and at low doses; others found no effect or strain/sex dependence), and crucially there is no human trial showing selegiline extends lifespan or healthspan.
As a drug it is generally well tolerated at low doses, but it is still an MAO inhibitor — at higher doses it loses MAO-B selectivity, creating risk of hypertensive (tyramine 'cheese') reactions and serotonin syndrome with serotonergic drugs (SSRIs, meperidine, etc.).
Selegiline is a prescription medication used off-label for longevity/neuroprotection; it is not a dietary supplement. The score reflects a plausible neuroprotective mechanism and mixed animal lifespan data against no human longevity evidence and real MAO-inhibitor interaction risk.
Selegiline irreversibly inhibits monoamine oxidase B, preserving dopamine and reducing the hydrogen peroxide and aldehydes generated by its breakdown.
Independently of MAO inhibition it upregulates superoxide dismutase and catalase, a proposed contributor to its neuroprotective and longevity effects.
Propargylamine activity reduces apoptotic signaling in neuronal models — the basis of its Parkinson's and neuroprotection rationale.
How Selegiline works — from molecular targets to health outcomes. Click an edge to see supporting research.This visualization is in beta — pathways are being refined and expanded.
Avoid — serious serotonin-syndrome risk.
Use caution; keep doses low and MAO-B-selective.
Avoid — not established as safe.
MAO inhibition plus serotonergic agents can cause life-threatening serotonin syndrome — a key contraindication.
At higher doses, loss of MAO-B selectivity risks hypertensive crisis with tyramine-rich foods or stimulants.
Tip: From amphetamine metabolites; dose earlier in the day.
Tip: Take with food; usually transient.
Tip: Avoid high doses, tyramine foods, and serotonergic drugs.
Selegiline has an evidence score of 3.5/10 — emerging evidence based on 65 indexed studies, including 1 meta-analysis. An MAO-B-inhibitor drug approved for Parkinson's disease and depression, long studied as a longevity/neuroprotection agent. It extended lifespan in some rodent studies (with mixed results across labs), but there is no human longevity evidence, and it carries MAO-inhibitor interaction risks. A prescription drug used off-label, not a supplement. Representative study: PMID 40816452.
The commonly studied dose of Selegiline is Off-label longevity use mirrors low Parkinson's dosing (e.g. ~5 mg/day, kept low to preserve MAO-B selectivity) under a clinician. Approved Parkinson's dose is 5 mg twice daily; the transdermal patch (depression) is dosed differently. Not an approved longevity regimen.. Individual needs vary — start at the lower end of the range and adjust based on how you respond.
The best time to take Selegiline is in the morning. Take it with food. Often dosed earlier in the day (it has stimulant-like amphetamine metabolites); keep the dose low to stay MAO-B-selective and avoid tyramine reactions.
Selegiline should be used with caution — talk to a healthcare provider before taking it. The most commonly reported side effects are insomnia / stimulation, nausea / dizziness, hypertensive reaction / serotonin syndrome. Use caution if any of these apply to you: Concurrent serotonergic drugs (SSRIs/SNRIs, meperidine, tramadol, dextromethorphan); Pregnancy / breastfeeding; Pheochromocytoma.
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Reviewed by Dr. Baher Al Hakim · Last reviewed June 2026 · evidence from 172 studies · how we score · editorial policy
This information is for educational purposes only. It is not a substitute for professional medical advice. Always consult a qualified healthcare provider before starting, stopping, or changing any supplement or medication.
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