Rasagiline: A Selective MAO-B Inhibitor for Parkinson's Disease
Rasagiline is a second-generation, selective, irreversible monoamine oxidase type B (MAO-B) inhibitor primarily used for the treatment of idiopathic Parkinson's disease, both as monotherapy in early disease and as adjunctive therapy with levodopa in moderate to advanced disease.
Mechanism of Action
- Rasagiline selectively inhibits MAO-B, an enzyme that breaks down dopamine in the brain 1
- This inhibition increases extracellular levels of dopamine in the striatum, enhancing dopaminergic activity 1
- Unlike first-generation MAO-B inhibitors like selegiline, rasagiline does not metabolize to amphetamine derivatives but rather to aminoindan, a non-amphetamine compound 2, 3
- Rasagiline is 5-10 times more potent than selegiline in inhibiting MAO-B 3
Clinical Applications
Early Parkinson's Disease
- Used as monotherapy in early Parkinson's disease
- Significantly attenuates worsening of symptoms compared to placebo 2
- Dosage: 1 mg once daily orally 4
Moderate to Advanced Parkinson's Disease
- Used as adjunctive therapy with levodopa
- Reduces daily "off" time by 0.49-0.94 hours compared to placebo 2
- Increases daily "on" time without troublesome dyskinesias 5
- Dosage: 0.5-1 mg once daily orally 4
Pharmacokinetics
- Rapidly absorbed through the gastrointestinal tract 4
- Readily crosses the blood-brain barrier 4
- Causes irreversible inhibition of MAO-B that lasts at least 1 week after the last dose 1
- A single 1 mg daily dose achieves 25-35% MAO-B inhibition, while 2 mg daily achieves >55% inhibition 1
- Multiple daily doses of 0.5-2 mg result in complete MAO-B inhibition 1
Safety Profile
- Generally well tolerated in clinical trials 2, 5, 6
- Adverse events similar in frequency to placebo or entacapone 2
- At recommended therapeutic doses (up to 1 mg daily), dietary tyramine restriction is unnecessary 1, 3
- However, certain foods with very high tyramine content (e.g., aged cheeses like Stilton) should be avoided as they could potentially cause severe hypertension 1
Important Considerations
- Selectivity for MAO-B diminishes in a dose-related manner as doses increase above 1 mg daily 1
- Elderly patients may be more prone to treatment-emergent cardiovascular and psychiatric effects 4
- Platelet MAO-B inhibition is irreversible and lasts at least 1 week after the last dose 1
- Potential neuroprotective properties have been demonstrated in experimental models, though clinical significance is still being investigated 2, 3
Advantages Over Other MAO-B Inhibitors
- Once-daily dosing provides a simple and convenient regimen 5, 6
- No amphetamine-like metabolites, unlike selegiline 2
- Complete and selective inhibition of MAO-B 3
Rasagiline represents an important therapeutic option for Parkinson's disease management, offering benefits across the disease spectrum with a favorable safety profile and convenient dosing schedule.