Selegiline’s Wide Array of Potential Therapeutic Effects

Selegiline is an irreversible monoamine oxidase (MAO) B inhibitor1. Monoamine neurotransmitters, such as serotonin, dopamine and norepinephrine, are derivatives of amino acids2. The enzyme monoamine oxidase A (MAO A) primarily oxidises (breaks down) serotonin and norepinephrine in the brain, whilst monoamine oxidase B (MAO B) primarily oxidises phenylethylamine, methylhistamine and tryptamine3. MAO A and B both break down dopamine and tyramine3. Inhibiting MAOs increases the amounts of monoamine neurotransmitters in the brain by preventing their breakdown3. MAO inhibitors (MAOIs) can be selective to either A or B variant of the enzyme at low doses but tend to lose selectivity to a specific MAO at higher doses3. Furthermore, MAOIs can bind to MAO reversibly or irreversibly to inhibit action of the enzyme4, with the latter tending to be more potent.

MAOIs have reduced in use over time due to the development of drugs which selectively target different neurotransmitters, as MAOIs can cause increased tyramine due to inhibiting its breakdown, and tyramine-induced hypertensive crisis can occur5. Due to this risk, a patient’s diet needs to closely monitored for tyramine-rich foods which is inconvenient, and many drug interactions can occur when an MAOI is used with another drug which affects neurotransmitter levels which can be potentially dangerous such as in cases of very high serotonin, or serotonin syndrome6.

Selegiline is an old discovery, and was first synthesised in 19621. It selectively targets MAO B at low doses, and also does not seem to dangerously increase tyramine levels causing hypertension when co-ingested with tyramine-rich foods; instead, it generally reduces blood pressure1. Furthermore, it is not liver toxic and seems to increase life expectancy in Parkinson’s disease (PD) patients1. In a study, it delayed the need for levodopa in PD by about 9 months when compared to antioxidant tocopherol, probably due to dopamine-increasing effects of the drug as seen in the post-mortem brains of selegiline-patients with elevated dopamine levels1. Additionally, selegiline by itself reduces oxidative stress acting as a neuroprotectant with neurotrophic and antiapoptotic activity1.

Selegiline also improves motor functions, memory functions and intelligence in PD patients7. In children with attention-deficit/hyperactivity disorder (ADHD), selegiline reduced ADHD symptoms by improving behaviour, attention and learning of new information without noted side effects8. In adolescents with depression, a significant reduction in depressive symptoms is seen using transdermal administration of selegiline9. When used to treat major depressive disorder (MDD), rather than causing sexual side effects like modern serotonin exposure-increasing antidepressants10, selegiline had a positive effect increasing scores on most sexual function tests11 likely due to its dopaminergic effects.

MAO-B inhibitors such as selegiline and rasagiline tend to slow the rate of progression of neurodegenerative diseases1, and both tend to have similar efficacy in treating PD12. However, in a mice model, selegiline exerted antidepressant effects unlike rasagiline even when both drugs were dose-matched for MAO inhibition13, suggesting even non-MAO inhibition related benefits of selegiline. Selegiline also increased synaptic plasticity in the medial prefrontal cortex of mice with mimicked PD13, potentially due to the observed positive effect of the drug on neurotrophic factors such as nerve growth factor, brain-derived neurotrophic factor and glial cell-derived neurotrophic factor14. Lastly, selegiline can be differentiated as a unique MAOI due to its interesting metabolites which include l-amphetamine-like and l-methamphetamine15, which may contribute to selegiline’s unique effects. Despite these metabolites, there has been suggested use for treating psychostimulant abuse and smoking cessation as selegiline is believed to have low abuse potential in a clinical setting15.



  1. Tábi, T., Vécsei, L., Youdim, M. B., Riederer, P., & Szökő, É. (2020). Selegiline: a molecule with innovative potential. Journal of neural transmission (Vienna, Austria : 1996)127(5), 831–842. 
  1. Science Direct 2021. Monoamine. Available online at  
  1. Sub Laban T, Saadabadi A. Monoamine Oxidase Inhibitors (MAOI) [Updated 2020 Aug 22]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: 
  1. Rudorfer MV. Monoamine oxidase inhibitors: reversible and irreversible. Psychopharmacol Bull. 1992;28(1):45-57. PMID: 1609042. Available online at  
  1. Sathyanarayana Rao, T. S., & Yeragani, V. K. (2009). Hypertensive crisis and cheeseIndian journal of psychiatry51(1), 65–66. 
  1. Science Direct 2021. Monoamine Oxidase Inhibitor. Available online at  
  1. Dixit SN, Behari M, Ahuja GK. Effect of selegiline on cognitive functions in Parkinson’s disease. J Assoc Physicians India. 1999 Aug;47(8):784-6. PMID: 10778622. Available online at  
  1. Rubinstein S, Malone MA, Roberts W, Logan WJ. Placebo-controlled study examining effects of selegiline in children with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol. 2006 Aug;16(4):404-15. DOI:  PMID: 16958566.  
  1. DelBello, M. P., Hochadel, T. J., Portland, K. B., Azzaro, A. J., Katic, A., Khan, A., & Emslie, G. (2014). A double-blind, placebo-controlled study of selegiline transdermal system in depressed adolescents. Journal of child and adolescent psychopharmacology24(6), 311–317. DOI: 
  1. Jing, E., & Straw-Wilson, K. (2016). Sexual dysfunction in selective serotonin reuptake inhibitors (SSRIs) and potential solutions: A narrative literature review. The mental health clinician6(4), 191–196. DOI: 
  1. Clayton AH, Campbell BJ, Favit A, Yang Y, Moonsammy G, Piontek CM, Amsterdam JD. Symptoms of sexual dysfunction in patients treated for major depressive disorder: a meta-analysis comparing selegiline transdermal system and placebo using a patient-rated scale. J Clin Psychiatry. 2007 Dec;68(12):1860-6. DOI: . PMID: 18162016. 
  1. Peretz, C., Segev, H., Rozani, V., Gurevich, T., El-Ad, B., Tsamir, J., & Giladi, N. (2016). Comparison of Selegiline and Rasagiline Therapies in Parkinson Disease: A Real-life Study. Clinical neuropharmacology39(5), 227–231. DOI:  
  1. Okano M.,Takahata K., Sugimoto J and Muraoka S. 2019. Selegiline Recovers Synaptic Plasticity in the Medial Prefrontal Cortex and Improves Corresponding Depression-Like Behavior in a Mouse Model of Parkinson’s Disease. Front. Behav. Neurosci., 02 August 2019. DOI:  
  1. Mizuta I, Ohta M, Ohta K, Nishimura M, Mizuta E, Hayashi K, Kuno S. Selegiline and desmethylselegiline stimulate NGF, BDNF, and GDNF synthesis in cultured mouse astrocytes. Biochem Biophys Res Commun. 2000 Dec 29;279(3):751-5. doi: . 4037. PMID: 11162424. 
  1. Yasar, S., Gaál, J., Panlilio, L. V., Justinova, Z., Molnár, S. V., Redhi, G. H., & Schindler, C. W. (2006). A comparison of drug-seeking behavior maintained by D-amphetamine, L-deprenyl (selegiline), and D-deprenyl under a second-order schedule in squirrel monkeys. Psychopharmacology183(4), 413–421. 


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