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

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.

Call 022-4897-1800

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NeuroPlus Epilepsy & Parkinson's Clinic - Dr. Kharkar IconNeuroPlus Epilepsy & Parkinson's Clinic - Dr. Kharkar

near LIC, Dr Balabhai Nanavati hospital, near LIC, Swami Vivekananda Road, LIC Colony, Vile Parle

4.6 87 reviews

  • Avatar Paras Prabhu ★★★★★ 6 months ago
    Out patient is epileptic from about 10 years and her seizure gotten worse during the past year with the frequency of about 3-4 times a week.So we consulted … More Dr. Kharkar. He tried a few medicines, and within 1.5-2 months now the patient is feeling very well now. There are no seizures for 14 days currently.Dr. tried to keep medicines as minimum as possible. He also tried to keep the cost of the treatment minimum.When some of the medicines started showing side-effects, he was quick to switch the medicines to the better options.Overall I think we are getting a best of the available treatments. We thank you very much Dr. Kharkar.
  • Avatar Dr Shobha Sankhe ★★★★★ a month ago
    Dr Kharkar is gem of a doctor with tremendous patience, empathy, genuine concern for his patients .He guides them very methodically & scientifically … More for their neurological ill healthOur epilepsy patient is extremely happy with his treatment , Patient feels better by just visiting him too!May his selfless service to humanity flourish to reach all the needy patients!!
  • Avatar shrruti khanna ★★★★★ a month ago
    I consulted Dr Sidharth for my sister who has become very hyper and aggressive and we could not understand the issue. Keeping in mind she is someone with … More special needs Dr Sidharth was extremely understanding of the situation and did not put her through unnecessary investigation and avoided a very long stay at the hospital. He was infact more keen on her returning home to her natural environment. We highly appreciate Dr Sidharth for his effort and for looking into the matter with utmost care. It was a very difficult decision for my family to get my sister admitted but we are glad we did it under his care.Thankyou Doc.
  • Avatar Prashant Purohit ★★★★★ a month ago
    my name is prashant purohit. I m become completely bed ridden from last 9 months and was unable to walk. I couldnt find out the cause even after visiting … More many doctors and many hospital in Ahmedabad nd jodhpur.started losing hope. A good friend of mine suggested to visit a neurologist. After searching a lot, I came to know about Dr. Siddharth Kharkar and took his appointment in Nanavati Hospital. He examined and said that he suffered from \u201cPKD(PAROXYSMAL KNESIGENIC DYSKNESIA\u201c. He assured us to reverse this in 5 days time. And indeed this happened. I started recovering miraculously. today I am fully well fit I m walking as normal . Many Many thanks to Dr. Siddharth Kharkhar sir for giving me a new life.
  • Avatar Sanjay Pradhan ★★★★★ 7 months ago
    Dr. Kharkar is truly exceptional. He is extremely knowledgeable. But simultaneously, he is extremely patient and kind - taking the time and care to respond … More to all the questions. It is rare to come across a doctor who is not in a hurry to get on to the next patient, but instead, focuses on the one in front with full attention, expertise and compassion. A great experience.
  • Avatar N N ★★★★★ a year ago
    We visited Dr. Kharkhar for treatment regarding my mum - who is a multi-stroke patient and has aphasia. Certain medications were creating complications … More with her condition and Dr. Kharkhar was able to help mitigate the issue. We found him and his approach to be incredibly compassionate, considerate, individualized and patient-friendly. He advice is astute, up-to-date and empathetic. His treatment always comes from a deeply human place and is about seeing how to help the patient and their caregivers feel more at ease. Something that is quite rare and refreshing within the medical community.We feel that he genuinely cares about the patients that he is treating and is always kind and respectful in his communication. Moreover, his admin team is very efficient and prompt and it's a pleasure to deal with them.Would highly recommend Dr Kharkhar himself - though we must say our experience with Nanavati hospital itself has been less than ideal.Hope this helps.
  • Avatar Manish Ranjan ★★★★★ a year ago
    I have been visiting Dr Kharkar for treatment of my father. He is a very friendly doctor. He listens to our concerns with lot of patience. He also explains … More the issue in much greater details. He has really been of great help. My father is much better now.
  • Avatar Pinakin Shah ★★★★★ 11 months ago
    One of the best Dr. Gives complete attention and time to listen to patient's history, issues. Explains various options of treatment with pros and … More cons.
  • Avatar Lawrence Castellino ★★★★★ a year ago
    Exceptional experience with an expert,Dr. Kharkar is a knowledge house. It is rare nowadays to find doctors with patience, knowledge, and a flair for … More handling patient’s questions, besides Dr. Kharkar’s bedside manners are exemplary. I am privileged to be treated by such an amazing soul. I have told him and will repeat it here that “I am advancing my move back to India although I am a US Citizen, because I know I am in good hands and will be well taken care of. Thanks Dr. Kharkar for your selfless service!
  • Avatar Hemant Kansara ★★★★★ a year ago
    Great doctor!! Really appreciate.The doctor diagnosed to my sister correctly and start treatment, she has good improvement after taking medicine prescribed … More by doctor as no epilepsy attake. We have good experience with the doctor. Thank you

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Outlook India Magazine - 2023Noted as one of the best Neurologists in Mumbai