Selegiline's Primary Role in Parkinson's Disease
Selegiline is a key component in the management of Parkinson's disease (PD), a progressive neurological disorder caused by the loss of dopamine-producing neurons. By inhibiting the enzyme monoamine oxidase B (MAO-B), selegiline prevents the breakdown of dopamine in the brain, thereby increasing its availability. This helps to alleviate the motor symptoms characteristic of PD, such as tremors, stiffness, and slow movement.
It is often used in combination with levodopa/carbidopa therapy for patients who experience a "wearing-off" effect, where the benefits of their medication diminish between doses. By extending the effects of levodopa, selegiline can help reduce these motor fluctuations and improve overall motor function. For some individuals with mild symptoms in the early stages of PD, selegiline may also be prescribed as a monotherapy to delay the need for levodopa, though its efficacy alone is generally considered less potent than levodopa itself.
Dosage Forms and Administration for PD
For Parkinson's disease, selegiline is available in several oral forms:
- Capsules and tablets (e.g., brand name Eldepryl, now generic): Typically taken twice a day, usually with breakfast and lunch.
- Orally disintegrating tablets (ODTs) (e.g., brand name Zelapar): A tablet that dissolves on the tongue once daily before breakfast, offering a different administration method for those who have trouble swallowing.
Selegiline for Major Depressive Disorder
In addition to its use in Parkinson's, a different formulation of selegiline is approved for the treatment of major depressive disorder (MDD) in adults. This is delivered via a transdermal patch (Emsam), which delivers a higher, more sustained dose of the medication directly into the bloodstream, bypassing the liver and intestinal tract. This transdermal delivery system provides a more non-selective inhibition of MAO (including MAO-A), which is necessary for its antidepressant effect, while minimizing the dietary restrictions typically associated with oral MAO inhibitors.
Antidepressant therapy with selegiline is often reserved for patients with treatment-resistant depression who have not responded to other antidepressants. Clinicians must carefully weigh the risks and benefits and closely monitor patients for side effects.
Mechanism of Action: How Selegiline Works
Selegiline's therapeutic effects are rooted in its action as a monoamine oxidase (MAO) inhibitor. MAO is an enzyme that metabolizes monoamines, including dopamine, norepinephrine, and serotonin. There are two types of MAO: MAO-A and MAO-B.
- Selective MAO-B Inhibition: At the lower doses used for PD (e.g., 10 mg daily), selegiline primarily inhibits MAO-B, which is the main enzyme responsible for breaking down dopamine in the brain. This increases dopamine levels in the brain's motor centers, helping control movement symptoms. At these lower doses, it does not significantly inhibit MAO-A in the gut, reducing the risk of a dangerous hypertensive crisis from consuming tyramine-rich foods.
- Non-Selective MAO Inhibition: At the higher doses delivered by the Emsam transdermal patch for depression, selegiline also inhibits MAO-A, which metabolizes other neurotransmitters like norepinephrine and serotonin. This broader effect is key to its antidepressant properties, though it necessitates careful dietary restrictions to prevent hypertensive crises.
Beyond MAO-B Inhibition
Beyond its primary MAO-B inhibition, selegiline also has other neuropharmacological effects, including:
- Enhancing dopamine release and blocking its reuptake.
- Producing amphetamine-like effects through its metabolites, l-amphetamine and l-methamphetamine, which can sometimes contribute to side effects like insomnia and anxiety.
- Exhibiting neuroprotective properties in preclinical studies, though this effect has not been conclusively proven in human clinical trials.
Selegiline vs. Rasagiline: A Comparison
Selegiline is not the only MAO-B inhibitor used for Parkinson's disease. Another common option is rasagiline (Azilect), which offers a different profile. A comparison helps clarify the choices available to patients.
| Feature | Selegiline (Eldepryl, Zelapar) | Rasagiline (Azilect) |
|---|---|---|
| Mechanism | Irreversible, selective MAO-B inhibitor at low doses; non-selective at higher doses | Irreversible, highly selective MAO-B inhibitor |
| Metabolites | Metabolized into L-amphetamine and L-methamphetamine | Not metabolized into amphetamine derivatives |
| Dosage Frequency | Varies by formulation; tablets/capsules twice daily, ODT once daily | Once daily |
| Formulations | Capsules, tablets, orally disintegrating tablets (ODT), transdermal patch | Tablets only |
| Tyramine Restrictions | Minimal at lower PD doses; required with higher transdermal patches for depression | Minimal at standard doses |
| Typical Cost | Often more affordable, especially generics | Generally more expensive, though generic is available |
Side Effects, Interactions, and Precautions
Like all medications, selegiline has potential side effects, which can vary depending on the dosage form and individual. Common side effects of oral selegiline can include:
- Nausea
- Dizziness or lightheadedness, especially when standing (orthostatic hypotension)
- Dry mouth
- Trouble sleeping or unusual dreams
- Headache
More serious side effects are possible and require immediate medical attention, including:
- Severe changes in blood pressure (hypertensive crisis), often linked to drug or food interactions.
- Serotonin Syndrome: A potentially life-threatening condition caused by combining selegiline with other medications that increase serotonin levels, such as certain antidepressants.
- Impulse-Control Disorders: Increased urges related to gambling, shopping, eating, or sex.
- Hallucinations or confusion, especially when taken with levodopa.
- Neuroleptic Malignant Syndrome (NMS): A serious withdrawal symptom if discontinued abruptly.
Important Drug and Food Interactions
Selegiline interacts with numerous drugs, including:
- Other MAO Inhibitors: Combining selegiline with other MAOIs is contraindicated due to the risk of hypertensive crisis.
- Certain Antidepressants: SSRIs, SNRIs, and TCAs can lead to serotonin syndrome when taken with selegiline. A washout period is necessary when switching between these medications.
- Opioids: Especially meperidine, methadone, and tramadol, due to the risk of fatal serotonin syndrome.
- Sympathomimetics: Including stimulants and certain cold and allergy medications containing ephedrine or pseudoephedrine.
- Dextromethorphan: A common ingredient in cough medicines.
Dietary restrictions regarding tyramine-rich foods are crucial at higher doses, such as those used for depression, and should be discussed with a doctor for any use of selegiline.
Conclusion
Selegiline is a valuable monoamine oxidase inhibitor with distinct applications in neurology and psychiatry. For Parkinson's disease, it serves as an adjunct therapy to extend the effectiveness of levodopa and helps manage motor symptoms. In its transdermal form, it is an option for treating major depressive disorder in specific patient populations. Its mechanism of action, involving the inhibition of MAO-B at low doses and becoming less selective at higher doses, underscores the importance of precise dosing and strict adherence to medical guidance. Given the potential for significant drug and food interactions, comprehensive patient education and careful medical supervision are essential for safe and effective treatment with selegiline.
