Parkinson's Disease
MAO-B Inhibitors
Monoamine oxidase B acts in the brain to degrade dopamine. Thus, inhibiting MAO-B is a therapeutic strategy for treatment of PD. Two selective MAO-B inhibitors are available in the United States and elsewhere: selegiline and rasagiline. Both are irreversible inhibitors of the enzyme.
Rasagiline
Rasagiline (Azilect®) is approved for the treatment of signs and symptoms of Parkinson's disease as initial monotherapy and as adjunct therapy to levodopa. It is available in 0.5 mg and 1.0 mg tablets. As monotherapy, it may reduce parkinsonian disability. As adjunctive therapy, it may reduce off time and increase dyskinesia-free on time. As monotherapy, the recommended dose is 1.0 mg once daily. As adjunctive therapy, the recommended dose is 0.5 mg once daily, with the option of increasing to 1.0 mg daily if sufficient clinical response is not obtained with the lower dose. The risk of hypertensive crisis increases above the prescribed dose. Side effects include insomnia, hallucinations, and orthostatic hypotension.
Selegiline
Selegiline is available as a swallowed pill (Eldepryl® and generics), and as an orally disintegrating tablet (ZelaparŪ ODT), which is not swallowed and does not require water. Selegiline is approved for the treatment of signs and symptoms of Parkinson's disease as initial monotherapy and as adjunct therapy to levodopa. As monotherapy, it may reduce parkinsonian disability. As adjunctive therapy, it may reduce off time and increase dyskinesia-free on time.
Selegiline in pill form is dosed at 5 mg once daily. Zelapar is dosed at 1.25-2.5 mg once daily. The risk of hypertensive crisis increases above the prescribed dose. Side effects include insomnia, hallucinations, and orthostatic hypotension.
Hypertensive Crisis
Nonselective MAO inhibition (i.e., inhibition of both MAO-A and MAO-B) may lead to life-threatening hypertensive crisis when tyramine-containing foods or drugs are consumed. While selegiline and rasagiline are selective MAO-B inhibitors, at doses above the prescribed dose, the risk of hypertensive crisis increases. Foods to avoid include air-dried or fermented meats, pickled herring, fava beans, soy beans and soy products (including soy sauce), aged cheeses, red wine, non-pasteurized beer, sauerkraut, and yeast extracts. Drugs to avoid include sympathomimetic amines including pseudoephedrine, phenylephrine, phenylproanolamine, and ephedrine.
Research on Neuroprotection
Selegiline was the subject of a major neuroprotective trial in PD, the DATATOP trial. While the results appeared to indicate that selegiline slowed the disease, the time required to wash out selegiline's symptomatic effect was greater than the washout period allotted in the trial, thus making these results inconclusive.
In a 2004 trial of rasagiline with a different trial design, patients who were treated for rasagiline for 12 months had slightly better activities of daily living scores than those treated for only 6 months, suggesting the potential for a disease-modifying effect. This study will need to be repeated and expanded before firm conclusions can be drawn.
