Talk:Selegiline

Selegiline is a phenethylamine

Selegiline is an irreversible selective inhibitor of monoamine oxidase B (MAO-B). At higher doses, it loses its selectivity for MAO-B and starts inhibiting MAO-A as well.

MAO-B is the enzyme that converts dopamine to its neurotoxic metabolites. Preventing this process is the primary source of selegiline's neuroprotective effects. When MAO-B is inhibited, dopamine is metabolized through other pathways. This results in elevated dopamine levels (more time before it gets metabolized), and lower dopaminergic neurotoxicity (metabolism through pathways that don't create the toxic metabolites).

Selegiline can be administered in a variety of ways. With oral administration, selegiline creates amphetamine metabolites, namely l-amphetamine and l-methamphetamine. With buccal administration, thee amount of amphetamine metabolites is significantly diminished by skipping first-pass metabolism. It also appears that buccal administration is eight times more effective at inhibiting MAO-B than oral administration.^[1]

It's not clear whether MAO-B is a necessary enzyme. Transgenic mice that are unable to produce MAO-B are shown to be resistant to a mouse model of Parkinson's disease. They also demonstrate increased responsiveness to stress (as with MAO-A knockout mice) and increased β-PEA. In addition, they exhibit behavioral disinhibition and reduced anxiety-like behaviors.

While people lacking the gene for MAO-A display mental retardation and behavioral abnormalities, people lacking the gene for MAO-B display no abnormalities except elevated phenethylamine levels in urine.

Inhibition of MAO-B in rats has been shown to prevent many age-related biological changes such as optic nerve degeneration, and extend average lifespan by up to 39%. This may be explained by a reduction in oxidative stress. Selegiline treatment seems to increase superoxide dismutase^[2] levels. This may be an indirect effect of preventing dopamine metabolism through MAO-B, which creates reactive oxidative species. This reduced oxidative stress would make the body more effective at fighting other oxidative stress, by having fewer antioxidant enzymes depleted.

Disclaimer: The effects listed below cite the Subjective Effect Index (SEI), an open research literature based on anecdotal user reports and the personal analyses of PsychonautWiki contributors. As a result, they should be viewed with a healthy degree of skepticism.

It is also worth noting that these effects will not necessarily occur in a predictable or reliable manner, although higher doses are more liable to induce the full spectrum of effects. Likewise, adverse effects become increasingly likely with higher doses and may include addiction, severe injury, or death ☠.

Experience reports

There are currently no anecdotal reports which describe the effects of this compound within our experience index. Additional experience reports can be found here:

• Erowid Experience Vaults: Selegiline

It is strongly recommended that one use harm reduction practices when using this substance.

At therapeutic doses, selegiline is not dangerous. Most of the dangers of selegiline come from MAO-A inhibition, which can be prevented in two ways.

1. Using low doses, such that selegiline remains selective to MAO-B
2. Using selegiline buccally, such that monoamine oxidase is not inhibited in the gut

MAO-A inhibition is dangerous when combined with specific foods, such as those high in tyramine (e.g. cheese). For this reason, keeping MAO inhibition out of the digestive tract, and keeping it selective to MAO-B prevents most of the dangers.

Lethal dosage

Tolerance and addiction potential

Dangerous interactions

Warning: Many psychoactive substances that are reasonably safe to use on their own can suddenly become dangerous and even life-threatening when combined with certain other substances. The following list provides some known dangerous interactions (although it is not guaranteed to include all of them).

Always conduct independent research (e.g. Google, DuckDuckGo, PubMed) to ensure that a combination of two or more substances is safe to consume. Some of the listed interactions have been sourced from TripSit. Combinations with the following substances can cause dangerously high serotonin levels. Serotonin syndrome requires immediate medical attention and can be fatal if left untreated.

• MAOIs - Such as banisteriopsis caapi, syrian rue, phenelzine, selegiline, and moclobemide.^[3]
• Serotonin releasers - Such as MDMA, 4-FA, methamphetamine, methylone and αMT.
• SSRIs - Such as citalopram and sertraline
• SNRIs - Such as tramadol and venlafaxine
• 5-HTP
• Amphetamine - Selegiline may increase the duration of amphetamines. It may decrease the neurotoxicity, but unexpected change in duration can be potentially dangerous.
• Cocaine

• Responsible use

• Selegiline (Wikipedia)
• Selegiline (Erowid Vault)
• Selegiline (TiHKAL / Isomer Design)
• L-Deprenyl (r/Nootropics FAQ)

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