Rasagiline — The Neuroprotective MAO-B Inhibitor
Rasagiline is a selective, irreversible MAO-B inhibitor primarily used to treat Parkinson's disease. In the context of longevity, it is of interest for its neuroprotective properties, which appear to be independent of its MAO-B inhibition and may help preserve neuronal function and mitochondrial integrity against age-related decline.
Mechanism of Action
Rasagiline is a potent, selective, and irreversible inhibitor of monoamine oxidase B (MAO-B), an enzyme that degrades dopamine in the brain. By inhibiting MAO-B, it increases extracellular dopamine levels in the striatum. Beyond MAO-B inhibition, rasagiline possesses a propargylamine moiety that exerts neuroprotective effects. It has been shown to prevent mitochondrial permeability transition pore opening, upregulate anti-apoptotic proteins like Bcl-2, and activate pro-survival pathways including PKC and MAPK, thereby protecting neurons from oxidative stress and apoptosis.
Human Trial Evidence
Rasagiline has been extensively studied in humans for Parkinson's disease. The ADAGIO trial (a delayed-start study) investigated its potential disease-modifying effects, finding that 1 mg/day, but not 2 mg/day, met all primary endpoints for slowing clinical progression, though the results were complex and debated. No published human longevity trials exist outside of neurodegenerative disease contexts.
Dosing Protocol
0.5–1 mg/day is the standard clinical dose for Parkinson's disease, typically taken once daily. It is a prescription-only medication. For neuroprotection or longevity purposes, dosing is unestablished, though 1 mg/day is the most studied dose in clinical trials.
Safety & Contraindications
Common adverse effects include headache, joint pain, indigestion, and depression. As an MAO-B inhibitor, it carries a risk of serotonin syndrome if combined with SSRIs, SNRIs, tricyclic antidepressants, or other serotonergic drugs. It is contraindicated with meperidine, tramadol, methadone, and other MAO inhibitors. Tyramine dietary restrictions are generally not required at the standard 1 mg dose, but caution is advised. Prescription required.