Talk:Selegiline: Difference between revisions

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==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==

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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===

===Tolerance and addiction potential===

===Dangerous interactions===

*'''[[Amphetamine]]'''

*'''[[Amphetamine]]''' - Selegiline may increase the duration of amphetamines. It may decrease the neurotoxicity, but unexpected change in duration can be potentially dangerous.

*'''[[Cocaine]]'''

@@ Line 19: / Line 19: @@
 ==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==
 {{EffectStub}}
@@ Line 69: / Line 80: @@
 {{toxicity}}
 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===
 ===Tolerance and addiction potential===
 ===Dangerous interactions===
 {{DangerousInteractions}}
 {{DangerousInteractions/Intro}}
 {{DangerousInteractions/SerotoninSyndrome}}
-*'''[[Amphetamine]]'''
+*'''[[Amphetamine]]''' - Selegiline may increase the duration of amphetamines. It may decrease the neurotoxicity, but unexpected change in duration can be potentially dangerous.
 *'''[[Cocaine]]'''