Selegiline is a monoamine oxidase-B (MAO-B) inhibitor used in the treatment of Parkinson's disease and major depressive disorder. It acts by irreversibly inhibiting the enzyme MAO-B, which metabolizes dopamine in the brain, thereby increasing dopamine availability and extending the duration of levodopa's effect.
| Property |
Value |
| Drug Class |
MAO-B Inhibitor |
| Approval Status |
FDA Approved (1989) |
| Brand Names |
Eldepryl, Zelapar, Emsam (transdermal) |
| Mechanism |
Irreversible MAO-B inhibition |
| Route of Administration |
Oral, Transdermal |
| Half-life |
1-2 hours (oral), 18-25 hours (transdermal) |
Selegiline selectively and irreversibly inhibits monoamine oxidase type B (MAO-B) in the brain:
- Dopamine Protection: MAO-B normally degrades dopamine; inhibition preserves endogenous dopamine
- Levodopa Enhancement: When combined with levodopa/carbidopa, selegiline allows for lower levodopa doses
- Neuroprotective Effects: May provide independent neuroprotective activity through antioxidant effects
- Metabolite Effects: Produces amphetamine metabolites (l-methamphetamine, l-amphetamine) at low doses
- Early Monotherapy: Used as initial treatment for mild PD symptoms
- Adjunct to Levodopa: Reduces "off" time and extends "on" time
- Motor Fluctuation Management: Helps manage wearing-off phenomenon
- Transdermal Form (Emsam): FDA-approved for treatment-resistant depression
- Low Risk of Tyramine Interaction: At low doses, does not require dietary restrictions
- Cognitive enhancement in Alzheimer's disease
- Narcolepsy management
- Binge eating disorder
| Parameter |
Value |
| Bioavailability |
~25% (oral) |
| Protein Binding |
~90% |
| Metabolism |
Hepatic (CYP450 enzymes) |
| Elimination |
Renal (~80%) |
| Duration of MAO-B Inhibition |
Irreversible (requires new enzyme synthesis, ~2 weeks) |
- Nausea, dry mouth
- Insomnia or sleep disturbances
- Headache
- Orthostatic hypotension
- Dyskinesia (especially with levodopa)
- Hypertensive crisis (with high-dose oral or tyramine-rich foods)
- Serotonin syndrome (when combined with SSRIs)
- Hallucinations or psychosis
| Interacting Drug |
Effect |
| SSRIs (fluoxetine, sertraline) |
Serotonin syndrome risk |
| Tyramine-rich foods |
Hypertensive crisis (high doses) |
| Meperidine |
Potentially fatal interaction |
| TCAs |
Serotonin syndrome risk |
- Long-term efficacy established in PD
- Once-daily oral dosing
- May slow disease progression (controversial)
- Transdermal option avoids first-pass metabolism
- Must be discontinued 2 weeks before SSRIs
- Dietary restrictions at higher doses
- Dyskinesia emergence with long-term use
- Limited efficacy as monotherapy in advanced PD
- DATATOP Study (1989): Selegiline delayed need for levodopa in early PD
- Pinkelman et al. (1995): Reduced off-time in levodopa-treated patients
- The Selegiline Research Group: Confirmed motor symptom improvement
- Neuroprotection: Investigating disease-modifying potential
- Combination Therapies: Studies with dopamine agonists
- Transdermal Delivery: Expanding use in depression
- Biomarker Studies: Identifying responders
The study of Selegiline Mao B Inhibitor For Parkinson'S Disease has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
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