What is an MAO-B Inhibitor?

Monoamine oxidase (MAO) is an enzyme found in mitochondria that exists in two forms: MAO-A and MAO-B.

MAO-A breaks down adrenalin, noradrena-lin, and serotonin, and is found predominantly in cells lining the gut, liver, and in neurons of the brain.

MAO-B breaks down dopamine and is found in the brain, primarily in the neurons of the substantia nigra.Drugs that block MAO-A, called MAO-A inhibitors are used to treat severe depression. Drugs that inhibit MAO-B increase dopamine in the brain and improve the symptoms of PD.

Selegiline (Eldepryl) was the first MAO-B inhibitor approved for use in PD. In a study conducted by Drs. Golbe, Muenter, and myself, selegiline (10mg/day) was shown to decrease “wearing off ” in patients taking levodopa.

Zelapar is a form of selegiline that dissolves on the tongue and is rapidly absorbed in the blood stream. Zelapar bypasses the stomach, intestines, and liver, and thus reaches the brain more rapidly. Because it increases and prolongs the effects of levodopa (either the levodopa normally formed in the neurons or the levodopa that is formed from carbidopa/levodopa), Zelapar decreases the “wearing off ” that occurs in all patients after they’ve been on levodopa for several months or years.

Rasagiline (Azilect) is another MAO-B inhibitor, developed by Dr. Moussa Youdim, a developer of selegiline. A clinical study by the Parkinson Study Group showed rasagiline to be effective in treating PD patients’ symptoms. Rasagiline can also be used as an adjunct to levodopa in patients with advanced PD and, like Zelapar, has shown to be effective in decreasing the wearing off of levodopa. A recent study suggests that rasagiline, started early, may delay the appearance of some of the symptoms of Parkinson disease. Additional studies are in progress to determine if rasagiline may delay the progression of Parkinson disease.

Rasagiline and selegiline used alone tend to delay the appearance of freezing of gait (FOG), a troublesome symptom of advanced PD. In patients who are already experiencing FOG the addition of these medications may reduce the FOG effects. Patients taking MAO-B inhibitors are cautioned about the interaction of these drugs with over-the-counter cold preparations, diet pills, and narcotic pain relief (such as Demerol). It is best to consult with your doctor regarding possible side effects.

In 1961, Walter Birkmayer was the first doctor to administer levodopa to PD patients. He subsequently reported, in 1986 (in the Journal of Neural Transmission), on a retrospective study of 941 patients he’d treated over 10 years. He reported that patients on deprenyl (selegiline) and levodopa lived longer than patients on levodopa alone. He postulated that selegiline had a neuroprotective effect: that it delayed the progression of PD. Subsequent studies showed that selegiline, given before MPTP, a toxin that causes a Parkinson-like disorder, blocked the development of PD in monkeys. These observations led, in 1987, to the DATATOP study, Deprenyl (selegiline) and Tocopherol (vitamin E) Antioxidative Therapy of Parkinsonism.

After 14 months of controlled observation, 10 mg of selegiline per day was found to significantly delay the time when enough disability developed to warrant the initiation of levodopa. The effect was sustained during the overall 8.2 years of observation. Most experts have interpreted the DATATOP study as showing that selegiline delays the time until levodopa is needed because selegiline itself has an anti-Parkinson effect. Some experts interpret DATATOP as suggesting selegiline is neuroprotective. Some experts also interpret a recent study, called ADAGIO, as suggestng that rasagiline may also be neuroprotective: that it may delay the progression of Parkinson disease.