MAO-B inhibitors: Rasagiline, Selegiline & Safinamide

Remember: Levodopa’s best friends are: Entacapone & Amantadine.

The medications discussed here (the MAO-B inhibitors) are also supposedly “friends of levodopa/dopamine”.

Except, two of them,  like the older brothers Karamazov, these medications are somewhat useful but full of flaws. These medications probably belong to an older generation. I use them very sparingly, if at all.

The newest amongst them, Safinamide, is a promising baby. Considering the reputation of its brothers, it’s difficult not to be slightly wary about it.

The flawed elder brothers: Rasagiline & Selegiline


Rasagiline & Selegiline are the bad brothers that you should probably avoid.

How do Rasagiline / Selegeline work?

Their mechanism of action is similar to Safinamide: They prevent the destruction of dopamine and therefore preserve it in the body, prolonging it’s action.


Two studies indicate that these medications may slightly slow the progression of Parkinson’s disease. However researchers and doctors have ferociously debated the results of these studies. Most doctors believe that there is either no effect, or a very minor effect that should not affect the choice of medication.

The effects of Rasagiline & Selegiline in slowing progression of Parkinson’s disease are very minimal. Many researchers believe there is no such effect.

Most doctors start by using levodopa (or rarely, the dopamine agonists) for a patient with newly diagnosed Parkinson’s disease. The thought process is as follows – Levodopa is the most potent medication for Parkinson’s disease. If I delay using levodopa, this patient will continue to have symptoms of Parkinson’s disease. Therefore, let me give him levodopa which I am sure will control most if not all of his symptoms, right now. These side-kicks are probably of no use in protecting the brain and produce too many side-effects.

It may be worthwhile, for the astute reader, to know about the details of these two studies:

  1. The ADIAGO study published in 2009 – Rasagiline at 1 mg per day seemed to slow Parkinson’s disease progression. But 2 mg per day had no beneficial effect! Many doctors believe that the positive result is just due to statistical chance, and is not real.
  2. The DATATOP study published in 1993 – Selegiline was useful in relieving the early symptoms of Parkinson’s disease, and therefore using the boss medication – levodopa – could be delayed by a few years.
    However, there was no direct comparison to the usual strategy of starting levodopa as the first medication. Although often cited as one of the studies that shows possible neuroprotection with these medications, it does not look at this question directly.


These medications have all of the same shortcomings as safinamide, except to a much greater degree.

  1. Sometimes they can cause or worsen high blood pressure
  2. They may occasionally cause liver problems.
  3. Some antidepressants including SSRIs (e.g. fluoxetine) and TCAs (e.g. amitriptyline, nortriptyline, amoxapine)
  4. Stimulants such as Amphetamine & Methlyphenidate
  5. Painkillers that contain opioids
  6. Some muscle relaxants such as cyclobenzaprine
  7. A few other medications such as the antibiotic linezolid.
  8. Fermented and pickled food e.g. fermented cheeses and Red Wine – these can cause a very uncomfortable, and occasionally serious condition called “Cheese reaction” due to accumulation of a chemical called tyramine in the body.
    The affected person has severe flushing of the skin, his/her heart starts beating faster, and he/she has a marked increase in BP. This can last hours – certainly not a good thing to go through!

    PanicAttack e1572183492876
    These medications can interact with fermented foods & cause a terrifying, very uncomfortable reaction.

    More importantly, they can interact with a large number of medications. You should avoid the following medications if you are taking rasagiline/selegiline:

The new kid on the block: Safinamide.

How does Safinamide act?

Safinamide acts just like Rasagiline and Selegiline. It inhibits an enzyme called MAO, which prevents the destruction of dopamine and keeps it in the body for a longer period of time.

It seems to be the less harmful brother of the older brothers Karamazov (Rasagiline & Selegiline), but only time will tell.

New Medication e1574183608197
This is 2019: Safinamide was released only 4 years ago. No one is perfectly sure how useful it will be.


  1. Since it is a very new medication, its uses are still being worked out. However, it seems to be effective in late-stage Parkinson's disease. Addition of Safinamide again seems to smoothen-out the effect of levodopa, so that patients experience fewer fluctuations in their functioning throughout the day.
  2. Safinamide is very unlikely to cause liver injury.
  3. Safnamide is less likely to interact with other medications. But you should probably avoid the medications mentioned above, if you can.
  4. Safinamide is less likely to interact with fermented foods. But perhaps it would be wise to avoid the foods mentioned above until we have more experience with the medications.


The side-effects of Safinamide seem to be the same as Rasagiline/Selegiline, but they occur less commonly.

  1. Just like its brothers, Safinamide can cause or worsen high blood pressure.


Caution: This information is not a substitute for professional care. Do not change your medications/treatment without your doctor's permission.
Dr. Siddharth Kharkar

Dr. Siddharth Kharkar

Dr. Siddharth Kharkar has been recognized as one of the best neurologists in Mumbai by Outlook India magazine and India today Magazine. He is a board certified (American Board of Psychiatry & Neurology certified) Neurologist.

Dr. Siddharth Kharkar is a Epilepsy specialist in Mumbai & Parkinson's specialist in Mumbai, Maharashtra, India.

He has trained in the best institutions in India, US and UK including KEM hospital in Mumbai, Johns Hopkins University in Baltimore, University of California at San Francisco (UCSF), USA & Kings College in London.

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