37 replies to this topic

[GABAergic]

so, about 9 years ago i remember lots of nootropic websites and forums talking about selegiline as being great and a lot of people taking it. now days searches on google show results from years ago and nobody discusses its effects today. what happened to it, did people just suddenly decide its not good and stop it? nobody discusses it at all and the searches on this forum show results as old as the google does. what really happened??

[GABAergic]

i guess that answered it. nothing! people just forgot and moved on. i love this forum! its so quick and easy and straight forward to get your answers here.

 

RIP selegiline, you had a good run on the forums once

 

ps: i wonder what is the new craze now

Edited by GABAergic, 18 February 2019 - 04:25 AM.

[maxwatt]

You have to hurry and try every new supplement while it still works.

[GABAergic]

or wait and see how well it fares in the long run. it seems they never do well long term. longest working supplement i know of is vitamin c and beyond that, everything has its end :/

[Kimer Med]

Selegeline -- better known as Deprenyl -- is still around. For those who may not have heard of it, it's an irreversible MAO-B inhibitor. MAO-B is responsible for breaking down dopamine, so inhibiting the enzyme results in higher levels of dopamine.

 

The research in this area is still relevant; MAO-B tends to increase in activity as we age, and mild inhibition starting at around age 45 seems to support longevity. However, there may be better (more accessible) ways to do that these days.

 

Here's a link to an article that describes the rise-and-fall of Deprenyl in more detail:

 

https://www.lifeexte...ng-Drug/Page-01

 

[GABAergic]

what are the better ways now days??

[Kimer Med]

what are the better ways now days??

 

Wild Green Oat Extract is one:

 

https://www.lifeexte...l-Being/Page-01

 

It blocks MAO-B, like Deprenyl.

[GABAergic]

i tried that one, felt absolutely nothing like deprenyl lol sorry to say. its kind of laughable such reputable site like lifeextension even compares it to deprenyl wow anyway thanks i guess

[GABAergic]

before i guess i fell for it without researching but i did now and it seems its just standardized content for isovitexin.

"Isovitexin (or homovitexin, saponaretin) is a flavone. the apigenin-6-C-glucoside. It can be found in the passion flower, Cannabis, and the açaí palm."

 

hmm couldnt find anything specific relaton to isovitexin and dopamine, but green oat extract has a lot of advertisement when i type isovitexin in the google. so basically the extract is made so isovitexin is the major biochemical, yet, no science behind isovitexin. very suspicious
 

[Kimer Med]

Interesting! Thanks for the follow-up.

 

Are you interested in an alternative to Selegiline because you don't have a source for it? Or some other reason?

 

FWIW, here's a link to one potential source:

 

https://shop.biogene...0mg-bottle.html

 

[GABAergic]

well, i used to get it in europe but i dont live there anymore but im always curious to try something more innovative and new in comparison.

i think selegiline is outdated now. maybe something that works similar way and it doesnt require strict diet when taking it.

anyway thanks for the link but wow its expensive and im not sure how good the liquid form can be. i remember this website from the past, they have really high prices on everything there.

but ill look forward to something similar but newer and hopefully people contribute more to this thread

[John250]

Rasagiline is supposed to be far better for MAO-B than Selegiline.

[GABAergic]

thats what i read too but for one rasagiline is really hard to get, and second but very importantly much higher price. good luck with that!

[CWF1986]

well, i used to get it in europe but i dont live there anymore but im always curious to try something more innovative and new in comparison.

i think selegiline is outdated now. maybe something that works similar way and it doesnt require strict diet when taking it.

anyway thanks for the link but wow its expensive and im not sure how good the liquid form can be. i remember this website from the past, they have really high prices on everything there.

but ill look forward to something similar but newer and hopefully people contribute more to this thread

 

Keep the dose 10mg or under which is way more than enough for life extension purposes and you don't have to do any dietary restrictions.  

[prunk]

Sorry for the off-topic question, but how stable selegiline is? I have almost a full bottle of it but EXP was 06/2016.

[xEva]

I tried both selegiline and rasagiline and rasagiline did nothing for me. I believe MAO-b inhibition is just one aspect of selegiline. Years ago I came across a couple of studies that speculated on off-target effects of selegiline, and one of them, if I remember correctly, had something to do with DNA repair (-?). And that well known amphetamine metabolite may have some positive effects too.

[GABAergic]

xeva, so you stopped them both altogether? do you find any good reason to restart with the selegiline?

[xEva]

Why stop? I merely tried rasagiline after reading that it was "just as good" but without the amphetamine metabolite of selegiline which could be a problem on drug tests. But it's just my personal experience. It may be that I do need that bit of amphetamine, which other people do not, 

 

In this regard, I wonder how it relates to the thread I noticed active recently (which I have not read yet) Amphetamine microdose sensitizes the dopamine system

 

I don't know how the quantities from microdosing compare to the quantities metabolized from, say 5mg selegiline,. Anyone knows?

Edited by xEva, 26 February 2019 - 04:36 AM.

[FunkOdyssey]

For most people and with longer term use, selegiline turned out to be a dead-end, just like all the other magic pills.  And whatever drug you're excited about today is the selegiline of tomorrow.  

[GABAergic]

wow thats dark funkodyssey. im sure some people benefited from it and are probably still benefiting we just cant find them to report. xEva said she had benefits, but i suppose she moved to other things because her life has changed. sometimes people just move on, get older and try different things/methods depending on their situation.

funkodyssey, am i to assume you have lost hope in supplements and medicine at this point?

Edited by GABAergic, 27 February 2019 - 02:44 AM.

[FunkOdyssey]

funkodyssey, am i to assume you have lost hope in supplements and medicine at this point?

 

Yes.  After enough years spent experimenting with drugs and supplements (15 in my case), and watching many, many others do the same, you will see a pattern emerge.  Pills are not an effective long-term solution for any form of mental or chronic illness.  The sooner you accept that, the better off you will be.  The only truly happy endings you will find involve people who have made significant changes to their diet and lifestyles.

[GABAergic]

yeah i can see that too. i spent 10 years with supplements, prescription drugs and illegal drugs and all kinds of alternative therapies with no long term benefit positive result. but in my case im an addict! thats why i keep doing it :/ i just cant walk by a store having those supps and pass them! damn

anyway, so you really dont take anything at all now? some supps can help, like vitamin d if you are deficient or some other mineral or vitamin depending on your condition or if you have a disease or take certain meds etc. i dont believe you dont take anything at all really

[gamesguru]

nobody discusses its effects today. what happened to it

 

Do not ascribe to failure and shame, what may be attributed to contented aloofness.

The main problem is finding the sweet spot. In my experience even low doses can have tianeptine-like trance and dream-like effects, and leave you feeling wiped out the next day. You can likely come off the rails if not taken with extreme care, this definitely happens with specific dopamine agonists used in Parkinson's.

Reports of Pathological Gambling, Hypersexuality, and Compulsive Shopping Associated With Dopamine Receptor Agonist Drugs
https://jamanetwork....article/1916909


Low-dose oral selegiline can likely be potentiated by grapefruit and other CYP inhibitors.

Opioid Toxidrome Following Grapefruit Juice Consumption in the Setting of Methadone Maintenance
https://pubmed.ncbi....h.gov/31206401/

Metabolism of selegiline hydrochloride, a selective monoamine b-type inhibitor, in human liver microsomes
https://pubmed.ncbi....h.gov/15618670/


Seems like it may have some benefits in ADHD as well.

Selegiline in the treatment of attention deficit hyperactivity disorder in children: a double blind and randomized trial
https://pubmed.ncbi....h.gov/12921918/


If the previous posts about dopamine sensitization are correct, it may have mild anti-addiction properties. Which is ironic, because at higher doses it becomes addictive itself.

1.25 mg every other day may be sufficient.

Longevity study with low doses of selegiline/(-)-deprenyl and (2R)-1-(1-benzofuran-2-yl)-N-propylpentane-2-amine (BPAP)
https://pubmed.ncbi....h.gov/27777099/

Edited by gamesguru, 26 May 2023 - 02:20 PM.

[edudix]

Deprenyl and the research done notably by Joseph Knoll meet scientific standards. In fact, it was the first drug that extended life expectancy in mammals (with beagle dogs and rats). This is one of the many factors that led me to investigate the relationship between dopamine and antiaging for more than 5 years. Personality traits such as extraversion, impulsiveness, and optimism correlate with the amount of dopamine and also with longevity. The loss of dopamine is one of the hypotheses about the causes of Alzheimer's, as indicated by the research of Marcello D´amelio. Having an ikigai, being motivated, maintaining enthusiasm as we age, getting involved in doing productive things, are all aspects that correlate with dopamine, which by the way we begin to lose after the age of 40. And why talk about depression, which accelerates aging and has already been shown to shorten our telomeres, and we know that a lack of dopamine and serotonin are essential in this sense. My research led me to write the book dopamine the secret weapon against aging that can be found on Amazon only in Spanish (Dopamina, el arma secreta contra el envejecimiento). It was hard work that was worth it, it allowed me to learn about the mechanisms that underlie aging and find out that, in addition to nutrition, physical exercise, etc. there could be a more novel factor. So in my opinion, yes, selegiline in particular and dopamine in general, they are not a silver bullet but they can greatly influence the way we age.

[gamesguru]

I remember reading that recent studies (since 2015 or so) have produced more modest, less impressive increases in lifespan than the ones in the 80s and 90s.

 

Recent evidence also suggests MAO-B only plays a minor role in stratial dopamine metabolism (with MAO-A supposedly being the major player).

 

Redefining differential roles of MAO-A in dopamine degradation and MAO-B in tonic GABA synthesis

https://www.nature.c...276-021-00646-3

 

This just highlights how little we really know, and how multiple mechanisms of effects can converge unexpectedly to produce a clear & desirable effect.

 

The mechanism of action of selegiline is complex and cannot be explained solely by its MAO-B inhibitory action. Pretreatment with selegiline can protect neurons against a variety of neurotoxins, such as 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP), 6-hydroxydopamine, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4), methyl-beta-acetoxyethyl-2-chloroethylamine (AF64A), and 5,6-dihydroxyserotonin, which damage dopaminergic, adrenergic, cholinergic, and sertoninergic neurons, respectively. Selegiline produces an amphetamine-like effect, enhances the release of dopamine, and blocks the reuptake of dopamine. It stimulates gene expression of L-aromatic amino acid decarboxylase, increases striatal phenylethylamine levels, and activates dopamine receptors. Selegiline reduces the production of oxidative radicals, up-regulates superoxide dismutase and catalase, and suppresses nonenzymatic and iron-catalyzed autooxidation of dopamine. Selegiline compensates for loss of target-derived trophic support, delays apoptosis in serum-deprived cells, and blocks apoptosis-related fall in the mitochondrial membrane potential. Most of the aforementioned properties occur independently of selegiline's efficacy to inhibit MAO-B.

 

 

I also read this article on Sci Hub. I am thinking to obtain powdered selegiline and dose it sublingually in 40% ethanol. Orally, it is practically a different drug. This review suggests that non-amphetamine metabolites may largely explain MAO-A inhibition at higher doses, and that 1.25 mg sublingually is quite similar (in terms of active drug) to 10 mg orally. That's an 8x increase in absorption efficiency.

 

Sci-Hub | A new formulation of selegiline: improved bioavailability and selectivity for MAO-B inhibition. Journal of Neural Transmission, 110(11), 1241–1255 | 10.1007/s00702-003-0036-4

 

In the present study, while administration of Zydis Selegiline 1.25 mg
was not associated with inhibition of MAO-A activity, repeated dosing with
Zydis Selegiline 10 mg or conventional selegiline tablets 10 mg, did cause some
inhibition of MAO, as evidenced by the significant decrease in 5-HIAA. How-
ever, this inhibition was not related to the concentration of selegiline in plasma.
It is, therefore, possible that the increased concentrations of metabolites result-
ing from conventional selegiline tablets 10 mg or Zydis Selegiline 10 mg may
resulted in a weak inhibition of MAO-A, which gradually developed on
repeated administration over 2 weeks.

 

[Galaxyshock]

Deprenyl and the research done notably by Joseph Knoll meet scientific standards. In fact, it was the first drug that extended life expectancy in mammals (with beagle dogs and rats). This is one of the many factors that led me to investigate the relationship between dopamine and antiaging for more than 5 years. Personality traits such as extraversion, impulsiveness, and optimism correlate with the amount of dopamine and also with longevity. The loss of dopamine is one of the hypotheses about the causes of Alzheimer's, as indicated by the research of Marcello D´amelio. Having an ikigai, being motivated, maintaining enthusiasm as we age, getting involved in doing productive things, are all aspects that correlate with dopamine, which by the way we begin to lose after the age of 40. And why talk about depression, which accelerates aging and has already been shown to shorten our telomeres, and we know that a lack of dopamine and serotonin are essential in this sense. My research led me to write the book dopamine the secret weapon against aging that can be found on Amazon only in Spanish (Dopamina, el arma secreta contra el envejecimiento). It was hard work that was worth it, it allowed me to learn about the mechanisms that underlie aging and find out that, in addition to nutrition, physical exercise, etc. there could be a more novel factor. So in my opinion, yes, selegiline in particular and dopamine in general, they are not a silver bullet but they can greatly influence the way we age.

 

Are you saying I can live to 120 as compulsive gambler high on L-DOPA? 

 

Seriously though, dopamine surely plays some part in aging and brain health, but I wouldn't just pick one neurotransmitter and think it's the holy grail. I am interested in what are safe ways to boost dopamine based on your research? Currently I supplement some L-Tyrosine but it's of course quite weak since it's just an amino acid.

 

I would like to try Selegiline but I don't think I can get it prescribed so I would have to obtain it through other means. I wonder if there's any natural MAOB-inhibitor that is effective and could provide similar benefits but in a smoother way.

[gamesguru]

Are you saying I can live to 120 as compulsive gambler high on L-DOPA? 

 

Seriously though, dopamine surely plays some part in aging and brain health, but I wouldn't just pick one neurotransmitter and think it's the holy grail. I am interested in what are safe ways to boost dopamine based on your research? Currently I supplement some L-Tyrosine but it's of course quite weak since it's just an amino acid.

 

I would like to try Selegiline but I don't think I can get it prescribed so I would have to obtain it through other means. I wonder if there's any natural MAOB-inhibitor that is effective and could provide similar benefits but in a smoother way.

 

Wild green oat extract was mentioned in this thread already.

 

Not sure how potent it is, but even low dose selegiline potentiates phenylalanine supplementation, and gives it that extra oomph.

 

I also quoted a study (see above) which contends that "The mechanism of action of selegiline is complex and cannot be explained solely by its MAO-B inhibitory action".  So oat extract may not at all resemble it clinically.

 

But dopamine is a sensitive system for sure. It has by far the fewest neurons of any major pathway, is the most sensitive to persistent down-regulation, and is the most consistently affected by environmental toxins and illicit drugs (e.g. MPTP, MDMA[1], methylmercury[2]). Of course you have things like domoic acid, DXM which affect glutamate too. So this is my no means a statistically significant sample size.

[Galaxyshock]

Wild green oat extract was mentioned in this thread already.

 

Not sure how potent it is, but even low dose selegiline potentiates phenylalanine supplementation, and gives it that extra oomph.

 

I also quoted a study (see above) which contends that "The mechanism of action of selegiline is complex and cannot be explained solely by its MAO-B inhibitory action".  So oat extract may not at all resemble it clinically.

 

But dopamine is a sensitive system for sure. It has by far the fewest neurons of any major pathway, is the most sensitive to persistent down-regulation, and is the most consistently affected by environmental toxins and illicit drugs (e.g. MPTP, MDMA[1], methylmercury[2]). Of course you have things like domoic acid, DXM which affect glutamate too. So this is my no means a statistically significant sample size.

 

Right, I should have read the whole thread before replying. I think Fo-Ti is another MAOB-inhibitor herb with also longevity-promoting claims. But go figure if it really works.

 

Yeah I've heard phenylalanine combines well with Selegiline.

[gamesguru]

Right, I should have read the whole thread before replying. I think Fo-Ti is another MAOB-inhibitor herb with also longevity-promoting claims. But go figure if it really works.

 

Yeah I've heard phenylalanine combines well with Selegiline.

 

Yeah, like I said, selegiline has many mechanisms of action; it is practically a distant cousin of rasagiline (which it ought to be an immediate twin of, if the "single mechanism" line of thinking were correct).

It's also greatly reduced my need or desire for caffeinated substances, down from 5 cups of strong tea to just 1 or 2. And I've only been taking a quarter pill orally a few times a week.

The extra dopamine can feel spacey or derealizing. But other times can feel motivating, creative. If you're not off, you're on.

[gamesguru]

Looks like it boosts NGF and GDNF, selegiline is a rare beast indeed.

 

Selegiline and Desmethylselegiline Stimulate NGF, BDNF, and GDNF Synthesis in Cultured Mouse Astrocytes
https://www.scienced...006291X00940373

 

That paper is from 2000, but I originally read about it from combing a more recent one (21 Sept 2022),

 

This paper presents the molecular mechanisms of neuroprotection by the inhibitors of type B monoamine oxidase, rasagiline and selegiline. They prevent mitochondrial apoptosis, induce anti-apoptotic Bcl-2 protein family, and pro-survival brain- and glial cell line-derived neurotrophic factors. They also prevent toxic oligomerization and aggregation of α-synuclein.

 

Interestingly, GDNF upregulation is a mechanism selegiline shares with naringin (found in grapefruit). Curiously, they both have potential in treating Parkinson's.

 

Naringin protects the nigrostriatal dopaminergic projection through induction of GDNF in a neurotoxin model of Parkinson's disease
https://pubmed.ncbi....h.gov/24797334/

Edited by gamesguru, 07 June 2023 - 02:49 AM.