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Selegiline
Quick Facts
- Generic Name
- Selegiline
- Brand Names
- Eldepryl, Zelapar
- Drug Class
- MAO-B inhibitor
- FDA Approved
- 1989
How It Works
Selegiline is a selective, irreversible monoamine oxidase type B (MAO-B) inhibitor that was the first drug in this class approved for Parkinson's disease. By inhibiting MAO-B, it slows the enzymatic breakdown of dopamine in the brain, modestly increasing dopamine availability. The orally disintegrating tablet form (Zelapar) is absorbed through the oral mucosa, bypassing first-pass liver metabolism and achieving higher brain concentrations at lower doses.
What to Expect as a Patient
Selegiline is typically well tolerated. When taken as prescribed (5mg twice daily with breakfast and lunch, never in the evening), most people experience few side effects. The most common complaints are trouble sleeping and dry mouth. If taking the Zelapar dissolving tablet, place it on your tongue in the morning before breakfast — do not eat or drink for 5 minutes. Be aware that selegiline can cause a positive result on workplace drug tests for amphetamines due to its metabolites. Report this to your employer/testing facility in advance. As with all MAO-B inhibitors, avoid meperidine (Demerol) and discuss all other medications with your doctor.
Typical Dosing
Conventional tablets: 5mg twice daily (breakfast and lunch — avoid evening doses to prevent insomnia). Zelapar (orally disintegrating): 1.25mg once daily in the morning, placed on the tongue before breakfast; may increase to 2.5mg after 6 weeks.
Dosing is individualized by the prescribing physician. The information above is for general reference only.
Common Side Effects
- Insomnia
- Nausea
- Dizziness
- Dry mouth
- Headache
Serious Side Effects
Seek medical attention immediately if you experience any of the following:
- Serotonin syndrome
- Hypertensive crisis with tyramine at supratherapeutic doses
Contraindications
- Meperidine
- Other MAO inhibitors
- Concurrent SSRIs require caution
Food Interactions
Avoid taking in the evening to reduce insomnia. Metabolized to L-amphetamine and L-methamphetamine derivatives, which may cause positive drug screens. These metabolites contribute to the stimulant-like side effects (insomnia, appetite suppression) not seen with rasagiline.
Drug Interactions
The following interactions have been documented with Selegiline. Always inform your healthcare provider about all medications you are taking.
Selegiline inhibits MAO-B, reducing dopamine breakdown and potentially increasing levodopa-related side effects.
Clinical effects: Increased dopaminergic effects, potential for orthostatic hypotension.
Management: May need to reduce levodopa dose by 10-30%. Avoid selegiline doses above 10mg/day to maintain MAO-B selectivity.
Concurrent use of two MAO inhibitors significantly increases risk of hypertensive crisis and serotonin syndrome.
Clinical effects: Severe hypertension, serotonin syndrome, potentially fatal.
Management: Never use concurrently. Allow adequate washout period when switching (at least 14 days).
Two MAO-B inhibitors must never be combined due to risk of excessive monoamine oxidase inhibition.
Clinical effects: Hypertensive crisis, serotonin syndrome if combined with serotonergic agents, potentially fatal.
Management: Never combine. Allow at least 14 days washout when switching between MAO-B inhibitors.
How Selegiline Compares to Alternatives
Selegiline was the first MAO-B inhibitor approved for PD and paved the way for rasagiline and safinamide. Compared to rasagiline: selegiline is available in a lower-cost generic but produces amphetamine metabolites (causing insomnia and potential false-positive drug screens); rasagiline has a cleaner metabolic profile and simpler once-daily dosing. Compared to safinamide: selegiline can be used as monotherapy while safinamide is approved only as adjunct to levodopa. The Zelapar (ODT) formulation bridges some gaps by achieving higher brain levels at a lower dose, but it is more expensive. All three MAO-B inhibitors provide similar magnitude of symptomatic benefit.
When Is Selegiline Used by Disease Stage?
Early PD (Stages 1-2): Can be used as initial monotherapy to delay the need for levodopa. The DATATOP trial showed it postponed levodopa need by approximately 9 months. Most practical when symptoms are mild. Mid-stage PD (Stage 2.5-3): Added to levodopa as adjunctive therapy to extend on-time. Provides modest off-time reduction. Advanced PD (Stages 4-5): Minimal additional benefit; may be continued as part of an established regimen but is rarely initiated at this stage.
Additional Notes
One of the oldest MAO-B inhibitors for PD (FDA approved 1989). The DATATOP trial was a landmark study that showed selegiline delayed the need for levodopa by approximately 9 months, though it did not conclusively prove neuroprotection. Often used as adjunct to levodopa to extend its effectiveness.
Clinical Perspective
Selegiline holds a historic place in PD pharmacotherapy as the drug that launched the neuroprotection investigation. The DATATOP trial (1989) was a watershed moment: its apparent protective effect drove a decade of research and hope, though subsequent analysis attributed most of the benefit to symptomatic rather than disease-modifying effects. In modern practice, selegiline has been largely supplanted by rasagiline (cleaner metabolism, once-daily dosing) for new prescriptions, but it remains a reasonable and cost-effective option, particularly in its generic form.
This perspective is based on published clinical evidence and guidelines. Individual treatment decisions should always be made with your neurologist.
Sources
- [1]Parkinson Study Group. Effect of deprenyl on the progression of disability in early Parkinson disease (DATATOP). N Engl J Med. 1989;321(20):1364-1371
- [2]Parkinson Study Group. Impact of deprenyl and tocopherol treatment on Parkinson disease in DATATOP subjects not requiring levodopa. Ann Neurol. 1996;39(1):29-36
- [3]Clarke CE. Are delayed-start design trials to show neuroprotection in Parkinson disease fundamentally flawed? Mov Disord. 2008;23(6):784-789
- [4]Connolly BS, Lang AE. Pharmacological treatment of Parkinson disease: a review. JAMA. 2014;311(16):1670-1683
- [5]American Academy of Neurology. Practice guideline: dopaminergic therapy for motor symptoms in early Parkinson disease (reaffirmed February 2025). AAN Guideline 1043
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