Deprenyl — The MAO-B Inhibitor
Deprenyl (selegiline) is a selective monoamine oxidase B (MAO-B) inhibitor and catecholaminergic activity enhancer originally developed for Parkinson's disease. In longevity research, it is notable for being one of the first pharmacological agents shown to extend maximum lifespan in rodent models, likely by preserving dopaminergic tone and reducing oxidative stress in the aging brain.
Mechanism of Action
Deprenyl acts primarily as an irreversible and selective inhibitor of MAO-B, an enzyme that degrades dopamine and whose activity increases with age. By inhibiting MAO-B, it preserves striatal dopamine levels and reduces the production of neurotoxic hydrogen peroxide, a byproduct of monoamine metabolism. Additionally, at low doses, it functions as a catecholaminergic activity enhancer (CAE), amplifying the impulse-mediated release of dopamine and norepinephrine. It has also been shown to upregulate antioxidant enzymes such as superoxide dismutase (SOD) and catalase, providing neuroprotective effects independent of MAO-B inhibition.
Human Trial Evidence
No published human longevity trials. Animal/in-vitro evidence only. While extensively studied and FDA-approved for Parkinson's disease and major depressive disorder, its effects on human lifespan or healthspan in healthy aging populations have not been evaluated in controlled clinical trials.
Dosing Protocol
For anti-aging or neuroprotective purposes, off-label low doses of 1–5 mg/day are typically discussed, taken in the morning to avoid insomnia. For Parkinson's disease, the standard prescription dose is 5 mg twice daily (10 mg/day). As a prescription-only medication, its use requires medical supervision. Higher doses lose MAO-B selectivity and may inhibit MAO-A, requiring dietary tyramine restrictions.
Safety & Contraindications
Common adverse effects include insomnia, nausea, dizziness, and headache. Because it is a prescription MAO inhibitor, it carries significant risks of drug interactions, particularly with SSRIs, SNRIs, tricyclic antidepressants, and certain analgesics (e.g., tramadol, meperidine), which can precipitate fatal serotonin syndrome. At doses above 10 mg/day, it loses MAO-B selectivity, necessitating a low-tyramine diet to prevent hypertensive crisis.