## Mechanism of MAO-B Inhibitors in Parkinsonism **Key Point:** Selegiline is a selective, irreversible inhibitor of monoamine oxidase-B (MAO-B), the enzyme responsible for the catabolism of dopamine in the brain. ### How It Works By inhibiting MAO-B, selegiline: 1. Reduces the breakdown of dopamine in the striatum 2. Prolongs the duration of action of levodopa 3. Increases dopamine bioavailability at the synapse 4. May slow the progression of neuronal degeneration (neuroprotective effect — though debated) ### Clinical Use Selegiline is used as: - **Adjunctive therapy** with levodopa in advanced Parkinson's disease - **Monotherapy** in early-stage disease (mild symptoms) - A drug that can reduce motor fluctuations and "wearing-off" phenomena **High-Yield:** At doses ≤10 mg/day, selegiline is selective for MAO-B and does NOT inhibit MAO-A, avoiding the "cheese effect" (tyramine interaction) seen with non-selective MAOIs. ### Comparison with Other Antiparkinson Drugs | Drug | Mechanism | Class | |------|-----------|-------| | **Selegiline** | MAO-B inhibition | Enzyme inhibitor | | Levodopa | Dopamine precursor | Dopamine replacement | | Bromocriptine | D₂ receptor agonist | Dopamine agonist | | Trihexyphenidyl | Anticholinergic | Muscarinic antagonist | **Clinical Pearl:** Selegiline's neuroprotective properties and ability to reduce levodopa requirement make it particularly valuable in younger patients with early Parkinson's disease.
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