Commentary
Video
Using Amantadine ER and MAO-B Inhibitors to Optimize PD Care
Author(s):
Pagan talked about discussed pharmacokinetic-pharmacodynamic data supporting the use of amantadine ER for dyskinesia in Parkinson disease and compared the safety profiles of rasagiline and safinamide to guide add-on therapy decisions.
At the 2025 American Academy of Neurology Annual Meeting, held April 5-9, in San Diego, California, movement disorder expert Fernando L. Pagan, MD, sat down with NeurologyLive® to share some updates on therapeutics for managing motor fluctuations in Parkinson disease (PD) based presentations from meeting. Pagan highlighted real-world findings related to treatment use, including patient experiences, adherence strategies, and adverse effect management with these therapies.
In this segment, Pagan discussed recent data highlighting the benefits of amantadine delayed-release/extended-release for managing dyskinesias in PD, emphasizing its pharmacokinetic profile and clinical effectiveness. He also compared the 2 main MAO-B inhibitors—rasagiline and safinamide—noting their pharmacological differences, particularly safinamide’s reversible action and additional properties that may offer advantages for patients experiencing motor fluctuations or dyskinesias.
Transcript below edited for clarity.
Fernando L. Pagan, MD: So, we know that there is a formulation of amantadine—delayed release, extended release—and there's a great abstract showing that there's a correlation between the control of dyskinesias and the pharmacokinetic profile of this amantadine, delayed release, extended release. So, this is actually new data. We have seen previously from EASE LID-1, EASE LID-2, and then the open-label EASE LID-3 studies that amantadine extended-release, delayed-release formulation can significantly reduce dyskinesias, reduce OFF time, and improve ON time—mostly by modulating those NMDA receptors.
Now, this is a nice correlation with the pharmacokinetic profiles. Patients take this at bedtime—usually around 10 p.m.—and by the time they wake up in the morning, that's when we start to see the levels of amantadine in the plasma. And as those levels of amantadine remain in the plasma during the day, those patients had less dyskinesia. So, that's really exciting, I think, as a clinician who does use amantadine extended-release, delayed-release formulation. It's different from immediate-release amantadine. There's no data really to prove this with amantadine immediate release. So, it just shows the strength of this formulation, and to have the pharmacokinetic profile fit what we've seen in the clinical picture, I think is exciting. And again, this is a medication that can be offered to our patients who are having significant motor fluctuations.
So, we have 2 major MAO-B inhibitors—very selective MAO-B inhibitors—that we have in our clinics. The first is rasagiline, which is an irreversible inhibitor of monoamine oxidase B enzyme, and then the next one is safinamide. Safinamide is a reversible MAO-B inhibitor. Pharmacologically, the way that a neurologist can think of these 2 is like looking at the difference between aspirin and ibuprofen when you inhibit the cyclooxygenase enzyme in platelet activity. A medicine like aspirin irreversibly inhibits that cyclooxygenase enzyme for 9 days. For ibuprofen, it's reversible—but they both can inhibit platelet function. So those are the 2 main differences.
Rasagiline, for the lifespan of an MAO-B enzyme, irreversibly inhibits that enzyme, whereas safinamide is a reversible inhibitor. But as long as you're taking it daily, you're still inhibiting that MAO-B enzyme. What's a little bit different between the molecules is not only the irreversible or reversible action on monoamine oxidase B enzyme, but safinamide also has other attractive properties that we've seen in other papers. And in Europe, it’s actually one of the preferred MAO-B inhibitors—especially if somebody is having more motor fluctuations, especially dyskinesias. There is some sentiment that dyskinesias may be a little bit better modulated with safinamide over the traditional irreversible rasagiline.
Also, I think it's always important to see—sometimes you may be too potent with rasagiline and cause a little bit more orthostatic hypotension, especially with adjuvant use with carbidopa/levodopa. Maybe that's not as strong with safinamide. So, there are certain areas, certain times, where it may be more advantageous to use a reversible versus an irreversible inhibitor. But they are 2 great options to use. Safinamide’s properties are a little bit different than rasagiline, but I think when you're looking at adjunctive treatment, you really do have the opportunity to use rasagiline or safinamide.
And in certain instances—for me, especially if the person has more dyskinesias or may have more orthostatic hypotension in the clinical picture—I may choose to use safinamide over rasagiline in that scenario as adjunctive use.
