Selegiline – The Ultimate Guide For Recommended Use

What Is Selegiline?

 Selegiline (marketed under the name Emsam), is a prescription drug approved for many different things currently. It is often taken off-label as a nootropic. Although it’s not as popular as other nootropics, Selegiline is a safe and effective alternative for boosting mood.

Selegiline Is A Potent MAO-B Inhibitor

SSRI stands for selective serotonin reuptake inhibitor. This class of drugs inhibits the re-uptake of serotonin. After neurotransmitters have successfully diffused across the synapse, they are reabsorbed and repackaged into vesicles by neurons. The actual re-uptake is accomplished by the SERT (serotonin transporter), which moves serotonin from outside the cell into the intracellular space or cytoplasm. SSRIs boost serotonergic neurotransmission by preventing it from being cleared. Deprenyl focuses on this crucial neurotransmitter. Since serotonin is linked to mood, it is implicated in many common nootropics.

The “monoamine hypothesis” states that diminished monoamines like serotonin cause depression. This theory has been discredited as overly simplistic. It was misappropriated by pharmaceutical companies to market SSRIs as treatments for a “chemical imbalance” The reality is that the brain is not a hydraulic system containing different levels of neurotransmitter – it’s much more intricate.

SSRIs block the clearance of serotonin which prolongs its activity at the synaptic cleft. This enhancement of serotonergic signaling may have downstream effects like increased neurogenesis that improved mood symptoms. Like SSRIs, Selegiline boosts serotonin, but to a lesser degree. Selegiline increases the neurotransmitters in the synapse by deactivating particular enzymes responsible for degrading neurotransmitters. This enzyme is called monoamine oxidase (MAO) and it’s located adjacent to mitochondria. As the name implies, this enzyme is involved in the oxidation of monoamines.


The enzyme, Monoamine Oxidase (MAO), was discovered in 1928 by Mary Bernheim when she was preparing her doctoral dissertation at the University of Cambridge. Bernheim was a remarkable person who in addition to being a pilot and a flight instructor, published over 60 papers in her lifetime. Interestingly enough, her husband who she married on December 17, 1928, researched and studied the tuberculosis bacteria and went on to be nominated for the Nobel Peace Prize in 1940.

The enzyme comes in two forms: MAO-A and MAO-B. Both the A and B subtype can break down or metabolize tyramine, dopamine, and tryptamine. However, each enzyme also has specificity and can act on different substrates. For example, MAO-A also breaks down noradrenaline, adrenaline, melatonin, and serotonin while MAO-B can break down benzylamine and phenethylamine. Inhibiting MAO-B tends to boost catecholamines like dopamine. Instead of being metabolized, dopamine will remain intact and continue to stimulate dopamine receptors.


It boosts neurotransmitters by selectively inhibiting Monoamine Oxidase B. At high doses, it also inhibits Monoamine Oxidase A. Selegiline has additional advantages over other, more conventional nootropics. It has dopaminergic effects that can help with the anhedonic and motivation when one is in need of working.
In addition, by inactivating the enzyme, Monoamine Oxidase A (MAO-A), it reduces the generation of hydrogen peroxide (H2O2) – a free radical.

Levels of the enzyme MAO may increase with aging, so some researchers think that artificially offsetting this increase with drugs like selegiline might have an anti-aging effect or neuroprotective effect. Low-dose Selegiline is also popular among nootropics users as an alternative to common stimulants like caffeine.


A typical daily dose of Selegiline is 5-10mg and this will not require you to change your diet because it is considered to be a relatively low amount, therefore affecting only MAO-B.

Side Effects

Selegiline’s mechanism as an MAO-B inhibitor boosts dopamine and phenylethylamine (PEA). The latter is a natural amphetamine-like compound found in small amounts in chocolate. PEA normally has a rapid half-life (it’s degraded quickly). But if you take selegiline, there’s a sustained increase in PEA because it can’t be degraded as quickly by MAO-B. There are stories floating around the internet about people abusing PEA + selegiline for its euphoric effects, DO NOT TRY THIS AS IT CAN BE VERY DANGEROUS!

Dopamine regulates the 4 M’s: mood, memory, and movement, and motivation. Impaired dopamine function plays a role many functions. Most drugs of abuse (like opioids) hijack the reward circuitry to elicit dopamine release.

Tricyclic antidepressants (TCAs) became the preferred treatment method during the 1970s and 1980s. Soon enough even the TCAs were replaced. But, some people still take MAOIs despite their greater side effect burden because they may be more effective for some types of motivation improvement.

Safety Concerns

It’s advisable to be conscientious about your diet while taking Selegiline. This is especially true if you take enough Selegiline to inhibit MAO-A. Inhibiting MAO-A can lead to cardiovascular issues because you’re tampering the enzyme that processes vasopressors and tyramine. In this scenario, it is advised to stay away from foods high in vasopressors such as chocolate, alcohol, and aged cheeses.

Fortunately, Emsam or Selegiline at normal doses only affects MAO-B. Therefore it can be safely taken without following a tyramine-free diet. If you take higher doses, remain cautious and watch what you’re eating.



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