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Added some pharmacology context (ROA differences, MAO-A vs MAO-B context, explanation of the mechanisms behind the potential benefits)
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{{SummarySheet}}
{{SummarySheet}}
'''Selegiline''' is a drug mainly used for treatment of parkinson's disease. In more recent years, it has been used as a nootropic drug.
{{SubstanceBox/Selegiline}}
'''Selegiline''' is a drug mainly used for treatment of parkinson's disease and depression. In more recent years, it has been used as a nootropic drug.
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==Pharmacology==
==Pharmacology==
{{pharmacology}}
{{pharmacology}}
Selegiline exerts its action by inhibiting MAO-B, and at higher doses, MAO-A.
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.<ref>https://pubmed.ncbi.nlm.nih.gov/14628189/</ref>
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<ref>https://pubmed.ncbi.nlm.nih.gov/8602757/</ref> 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.
==Subjective effects==
==Subjective effects==
{{EffectStub}}
{{EffectStub}}
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===Experience reports===
===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:
There are currently {{#ask:[[Category:SUBSTANCE]][[Category:Experience]] | format=count}} experience reports which describe the effects of this substance in our [[experience index]].
* [https://www.erowid.org/experiences/subs/exp_SUBSTANCE.shtml Erowid Experience Vaults: SUBSTANCE] <!-- Check the link to see if it exists -->
==Toxicity and harm potential==
==Toxicity and harm potential==
{{toxicity}}
{{toxicity}}
It is strongly recommended that one use [[responsible use|harm reduction practices]] when using this substance.
It is strongly recommended that one use [[responsible 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.
# Using low doses, such that selegiline remains selective to MAO-B
# 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===
===Lethal dosage===
===Tolerance and addiction potential===
===Tolerance and addiction potential===
===Dangerous interactions===
===Dangerous interactions===
{{DangerousInteractions}}
{{DangerousInteractions}}
{{DangerousInteractions/Intro}}
{{DangerousInteractions/Intro}}
{{DangerousInteractions/SerotoninSyndrome}}
*'''[[Amphetamine]]''' - Selegiline may increase the duration of amphetamines. It may decrease the neurotoxicity, but unexpected change in duration can be potentially dangerous.
This article is in the 'Talk' namespace because it is an unfinished draft. This section is used to host drafts for unpublished articles as well as discussions for published ones. If you'd like to use this area to discuss this draft, please do so in the 'Discussion' section at the very bottom of the page. This notice will be removed once this draft has been approved for publication by an administrator.
It may contain incorrect information, particularly with respect to dosage, duration, subjective effects, toxicity and other risks. It may also not meet PW style and grammar standards.
WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section.
DISCLAIMER: PW's dosage information is gathered from users and resources for educational purposes only. It is not a recommendation and should be verified with other sources for accuracy.
Selegiline is a drug mainly used for treatment of parkinson's disease and depression. In more recent years, it has been used as a nootropic drug.
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 PsychonautWikicontributors. 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 ☠.
Physical effects
If applicable, a brief paragraph summary of the substance's physical effects may be included here.
You may select physical effects to add below here.
If applicable, a brief paragraph summary of the substance's cognitive effects may be included here.
You may select from a list of cognitive effects to add below here.
There are currently no anecdotal reports which describe the effects of this compound within our experience index. Additional experience reports can be found here:
This toxicity and harm potential section is a stub.
As a result, it may contain incomplete or even dangerously wrong information! You can help by expanding upon or correcting it. Note: Always conduct independent research and use harm reduction practices if 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.
Using low doses, such that selegiline remains selective to MAO-B
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.
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.
Amphetamine - Selegiline may increase the duration of amphetamines. It may decrease the neurotoxicity, but unexpected change in duration can be potentially dangerous.
. eISSN 1471-6771. ISSN 0007-0912. OCLC 01537271. PMID 16051647.