MAO-B inhibitors

How do they work?

In the brain, a substance (enzyme) called MAO-B (short for monoamine oxidase B) breaks down dopamine, thus preventing its action – a normal control mechanism. MAO-B inhibitors stop MAO-B from working, and this raises the levels of dopamine in the brain (see Figure, below).

Therefore, in Parkinson’s disease (PD), MAO-B inhibitors (e.g., rasagiline, selegiline) can be given to prevent dopamine being broken down – thereby prolonging the action of dopamine in the brain (including the dopamine provided by treatment with levodopa).

What are the benefits?

MAO-B inhibitors are useful in the very early stages of PD, and may be used as a first treatment – delaying the need for levodopa. When levodopa is required, MAO-B inhibitor treatment can be continued or newly added to the regimen, allowing a lower dose of levodopa to be used, and therefore helping to delay the start of the motor fluctuations that appear with long-term levodopa treatment.

There has been some discussion as to whether the MAO-B inhibitors protect brain cells and can slow down the progression of PD. This has been investigated in clinical trials with rasagiline, which indicate that it may be able to slow the progression of disease (although no medication is yet approved by the authorities for this use).

What are the side effects?

Rasagiline is generally well tolerated, with the most common side effects including headache (when taken alone, i.e., as monotherapy), dyskinesia, vomiting, constipation, accidental injury, and low blood pressure on standing (when taken together with levodopa).

Selegiline is also generally well tolerated, with dry mouth and sleeping disorders being some of the most common side effects. However, as it helps to increase the action of levodopa, selegiline also increases some of levodopa’s side effects such as dyskinesia, nausea, confusion, hallucinations, low blood pressure on standing, and vertigo. The increase in levodopa-related side effects may be alleviated by adjusting the levodopa dosage. Side effects of selegiline relating to the central nervous system (hallucination, confusion and changes in blood pressure) may be due to its breakdown product (amphetamine metabolite).

MAO-B inhibitor formulations

A practical advantage of the MAO-B inhibitor, rasagiline, is that it is taken as a once-daily dose, at any time of day, with or without food, and requires no titration (the gradual increase in dose that is sometimes used to find the most effective level of treatment), thus providing a convenient administration schedule.

A new tablet form of selegiline has been developed to quickly dissolve in the mouth – helping to avoid some of selegiline’s side effects, and also providing a useful method of administration for people with PD who have difficulty swallowing tablets.

How MAO-B inhibitors work

(Click on animation to enlarge.)