Selegiline Experiences

[Mauritio]

Very low dose is effective at increasing antioxidants enzyeme in the rat testes.
High dose not.

Low dose was an HED of 0.03mg per day. Which was administered intraperitoneally. Oral bioavailability is about 10% so that would be something similar intraperitoneally. Which is an insanely small amount.

Interestingly the high dose ,which was 100x higher , did not have any effects in that regard.

The effect of R-(-)-deprenyl administration on antioxidant enzymes in rat testis - PubMed

The aim of the study was to investigate the effect of R-(-)-deprenyl administration on the activity and localization of superoxide dismutases (SODs) and catalase (CAT) in rat testis. After 30 days of intraperitoneal administration of either saline (control) or R-(-)-deprenyl dissolved in saline...

pubmed.ncbi.nlm.nih.gov

There was a similar effect of the same dosages on antioxidants in the brain.
So microdosing selegiline might actually be a thing...

Effects of low and high deprenyl dose on antioxidant enzyme activities in the adult rat brain - PubMed

We evaluated the effects of low dose deprenyl (LDD, 0.0025 mg/kg per day) and high dose deprenyl (HDD, 0.25 mg/kg per day) treatment of male Wistar rats for 30 days on the activities of SOD and CAT in the cortex, striatum, and hippocampus. Total SOD and MnSOD activities were increased with LDD...

pubmed.ncbi.nlm.nih.gov

 

[Mauritio]

Although this study did find antioxidant benefits of the higher doses (HED=3mg) .

Age-related protective effect of deprenyl on changes in the levels of diagnostic marker enzymes and antioxidant defense enzymes activities in cerebellar tissue in Wistar rats - PubMed

Antioxidants are free radical scavengers and protect living organisms against oxidative damage to tissues. Experimental evidence implicates oxygen-derived free radicals as important causative agents of aging and the present study was designed to evaluate the age-related effects of deprenyl on...

pubmed.ncbi.nlm.nih.gov

 

[Mauritio]

The effective dose for longevity seems to vary a lot depending mostly on species but also gender and age.
Hard to predict exactly the right dose for humans.

Assessing the effects of deprenyl on longevity and antioxidant defenses in different animal models - PubMed

Among many pharmaceuticals that have been tested for their effects on longevities of different animal rodents, deprenyl is unique in that its effects on longevity has been tested in at least four different animal species by independent research groups and that the effect has been postulated to...

pubmed.ncbi.nlm.nih.gov

 

[Mauritio]

Very low dose is effective at increasing antioxidants enzyeme in the rat testes.
High dose not.

Low dose was an HED of 0.03mg per day. Which was administered intraperitoneally. Oral bioavailability is about 10% so that would be something similar intraperitoneally. Which is an insanely small amount.

Interestingly the high dose ,which was 100x higher , did not have any effects in that regard.

The effect of R-(-)-deprenyl administration on antioxidant enzymes in rat testis - PubMed

The aim of the study was to investigate the effect of R-(-)-deprenyl administration on the activity and localization of superoxide dismutases (SODs) and catalase (CAT) in rat testis. After 30 days of intraperitoneal administration of either saline (control) or R-(-)-deprenyl dissolved in saline...

pubmed.ncbi.nlm.nih.gov

There was a similar effect of the same dosages on antioxidants in the brain.
So microdosing selegiline might actually be a thing...

Effects of low and high deprenyl dose on antioxidant enzyme activities in the adult rat brain - PubMed

We evaluated the effects of low dose deprenyl (LDD, 0.0025 mg/kg per day) and high dose deprenyl (HDD, 0.25 mg/kg per day) treatment of male Wistar rats for 30 days on the activities of SOD and CAT in the cortex, striatum, and hippocampus. Total SOD and MnSOD activities were increased with LDD...

pubmed.ncbi.nlm.nih.gov

Selegiline seems to be pretty helpfull for fertility.

The effect of R-(-)-deprenyl administration on reproductive parameters of rat males - PubMed

The aim of the study was to investigate the effect of R-(-)-deprenyl administration on the reproductive parameters of rat males. After 30 days of intraperitoneal administration of saline or 0.0025mg/kg (10(-5)mol/l) of R-(-)-deprenyl dissolved in saline, males were mated with females of the same...

pubmed.ncbi.nlm.nih.gov

 

[golder]

Selegiline seems to be pretty helpfull for fertility.

The effect of R-(-)-deprenyl administration on reproductive parameters of rat males - PubMed

The aim of the study was to investigate the effect of R-(-)-deprenyl administration on the reproductive parameters of rat males. After 30 days of intraperitoneal administration of saline or 0.0025mg/kg (10(-5)mol/l) of R-(-)-deprenyl dissolved in saline, males were mated with females of the same...

pubmed.ncbi.nlm.nih.gov

Wow good find, that’s such a low dose. Do you think the low dose of 0.25mg for a 80kg male would be worth taking just for the antioxidant benefit?

 

[Mauritio]

Wow good find, that’s such a low dose. Do you think the low dose of 0.25mg for a 80kg male would be worth taking just for the antioxidant benefit?

The human dose for an 80kg person is about 0.03mg, while I take 1.5mg just for reference. And yes I think it could be worth it but good luck with the dosing such a small amount . Maybe volumetric dosing could help. But at that dose i think it's very safe.

 

[golder]

The human dose for an 80kg person is about 0.03mg, while I take 1.5mg just for reference. And yes I think it could be worth it but good luck with the dosing such a small amount . Maybe volumetric dosing could help. But at that dose i think it's very safe.

Thanks man. Have you looked at the profile of Rasagiline? I’m very curious how you think it would compare.

 

[Motorneuron]

Could it be useful in slowing down ALS?

 

[Mauritio]

Thanks man. Have you looked at the profile of Rasagiline? I’m very curious how you think it would compare.

Not a lot, so dont take my word for it. I have a lot of selegiline laying around so I dont see a need yet to look into it.

 

[TeslaFan]

Have you looked at the profile of Rasagiline?

Stronger, so much lower amount is needed.

 

[joaquin]

I tried deprenyl / selegiline 15 years ago. IIRC it was one mg a day perhaps. It made me cold all over and I didn't like the experience.

 

[Mauritio]

To extend life, first of all we have to prevent death.

We often seek to extend life, but why not first make sure you dont die prematurely.

I've been looking at the life extension studies on selegiline and while it is pretty successful at doing just that (increases of ~10-35%), this stufy showed it that it was really successful at making sure that no little rat died prematurely .
The most effective deprenyl/selegiline dose was 0.001mg... once again: the microdose.

The shortest living rat receiving microdose selegiline lived 69% longer than the shortest living rat receiving saline (control group). That's quite remarkable. No one's left behind with selegiline

However the average lifespan increase was greater using the 0.1mg/kg dose (12%) vs. The 0.001mg/kg dose (8%) .

As I previously posted: the microdose of selegiline is pretty effective in an HED of approximately 0.01-0.05mg (10-50mcg). it shows great capacity to increase antioxidants and lowers chances of death, while probably beeing super safe because of the low dose, so it could be taken indefinitely pretty safely, I guess.
I would look into volumetric dosing if I were to do that.

The reason for its effectiveness at the low dose is the so called "enhancer effect" , the author (knoll himself ! Knoll J, Miklya - Google Search ) describes its effect like that: "It is a remarkable
unique effect of the enhancer substances that they transform the silent dopaminergic neurons into spontaneously active entities [3]."
There is a whole rabbit whole of the enhancer substances that seems quite interesting...but that's for another post.

And the enhancer effect only happens at very low doses. Some experiments have shown a U-shaped effectiveness curve, with super low and medium doses beeing effective. And also good effectiveness at MAO-A-inhibiting territory a.k.a. very high doses , so the effectiveness curve actually looks more like W.
For example:

 

[NewACC]

The dose I take is for anti-aging (MAO-B inhibition), and not for depression. Also, in larger doses Selegiline can start inhibiting MAO-A, and I don't want that.

If you take it orally, you can up to 30-40mg and it'll still be pretty selective for mao-b or up to 7.5 mg if you use it sublingually

 

[TheCodez]

Keep in mind that if you are employed somewhere with drug tests, selegiline will show a positive for amphetamine.

 

[golder]

Keep in mind that if you are employed somewhere with drug tests, selegiline will show a positive for amphetamine.

That’s a very good point, thanks for sharing this important point. That’s why I was looking into Rasagiline as it doesn’t have the amphetamine metabolite. I was hoping someone with a better understanding of biochemistry could help ascertain if Rasagiline would still have the low dose benefits that Selegiline purports to have?

 

[ecstatichamster]

Might as well take a micro nibble on a 5mg pill and see what happens. To my rat. Probably 100 mcg just by eying it. Who knows.

 

[Mauritio]

That’s a very good point, thanks for sharing this important point. That’s why I was looking into Rasagiline as it doesn’t have the amphetamine metabolite. I was hoping someone with a better understanding of biochemistry could help ascertain if Rasagiline would still have the low dose benefits that Selegiline purports to have?

IIRC buccal /sublingual doesnt have the amphetamine metabolite as it skips the liver . Not sure if second pass metabolism is enough to show a positive effect.

Might as well take a micro nibble on a 5mg pill and see what happens. To my rat. Probably 100 mcg just by eying it. Who knows.

Good idea! I'm wondering if you'll feel anything with that low of a dose...

 

[Dave Clark]

Do these levels represent a weekly total, or an immediate dose? In other words, if you used 5 mg/week, and did small amounts daily is that better than doing 5 mg once/week? I know some people do half tablet a few times a week, and others a full tablet may once or twice/week.

 

[ecstatichamster]

IIRC buccal /sublingual doesnt have the amphetamine metabolite as it skips the liver . Not sure if second pass metabolism is enough to show a positive effect.

Good idea! I'm wondering if you'll feel anything with that low of a dose...

I have not. May hike to one mg a day for a bit.

 

[Mauritio]

To extend life, first of all we have to prevent death.

We often seek to extend life, but why not first make sure you dont die prematurely.

I've been looking at the life extension studies on selegiline and while it is pretty successful at doing just that (increases of ~10-35%), this stufy showed it that it was really successful at making sure that no little rat died prematurely .
The most effective deprenyl/selegiline dose was 0.001mg... once again: the microdose.

The shortest living rat receiving microdose selegiline lived 69% longer than the shortest living rat receiving saline (control group). That's quite remarkable. No one's left behind with selegiline
View attachment 47921
However the average lifespan increase was greater using the 0.1mg/kg dose (12%) vs. The 0.001mg/kg dose (8%) .

As I previously posted: the microdose of selegiline is pretty effective in an HED of approximately 0.01-0.05mg (10-50mcg). it shows great capacity to increase antioxidants and lowers chances of death, while probably beeing super safe because of the low dose, so it could be taken indefinitely pretty safely, I guess.
I would look into volumetric dosing if I were to do that.

The reason for its effectiveness at the low dose is the so called "enhancer effect" , the author (knoll himself ! Knoll J, Miklya - Google Search ) describes its effect like that: "It is a remarkable
unique effect of the enhancer substances that they transform the silent dopaminergic neurons into spontaneously active entities [3]."
There is a whole rabbit whole of the enhancer substances that seems quite interesting...but that's for another post.

And the enhancer effect only happens at very low doses. Some experiments have shown a U-shaped effectiveness curve, with super low and medium doses beeing effective. And also good effectiveness at MAO-A-inhibiting territory a.k.a. very high doses , so the effectiveness curve actually looks more like W.
For example:
View attachment 47920

I tried microdosing selegiline today.

I notice an increase in motivation, mood and focus.

I took a tiny nibble of my selegiline tablet, using my mg-scale, that roughly corresponds to about 30-40mcg of selegiline.
I took it orally since I'm not sure about sublingual administration because it could catapult you out of the effective dose range . 0.001mg/kg is effective (specific enhancer effect) , 0.01 mg/kg is ineffective, so dosage is important here.
I might try sublingual the next time,though.

I'm quite surprised that I notice any effects at all, since the dosage is about 50 times lower than what I usually take. Which isn't much to begin with.

The mechanism of action:

1. "The specific enhancer effect" as phrased by Knoll
(- https://www.google.com/url?sa=t&sou...gQFnoECAkQAQ&usg=AOvVaw131YXvj_95UeoWiJEkfZ_L)

2. Low doses of amphetamines/stimulants reverse tolerance and resensitize dopamine receptors semi-permanently without neurotoxicity

"Tests in human subjects has shown that after been given a low dosage of Amphetamine, the subjective high rating from a large dose of Amphetamine has nearly doubled. In rats, dopaminergic supersensitivity from low-dosage stimulant exposure lasts at least 12 days, and in primates, this hypersensitivity been demonstrated to last at least 2.5 years postwithdrawal."
- Amphetamine microdose sensitizes the dopamine system - Brain Health