Anyone taking Selegiline / Deprenyl For Longevity?

Hi Jay,

i apologize for the delay. I just went into the app and saw I have a draft that didn’t get sent,

I take started taking dopamine precursors because I got hired to measure how taking them changed EEG. I added myself to the study to increase the sample size and my nervous system loved it.

Later, I found I have a homozygous over active MAOa SNP than makes me break down dopamine which explains why I like dopamine agonists so much.

Mucuna at 15% l dopa 200 mg capsule am and noon
Tyrosine powder 1 tablespoon am and noon
Modafinil 100 mg am and noon

I have taken selegiline on an off for about 25 years. It is an MAOb antagonist. Until recently, MAOb was thought to oxidize dopamine because is efficacious for Parkinson’s. Newer research suggests the effect is from breaking down subcortical GABA. I posted an article on this.

I noticed that selegiline did not to reduce the amount of dopamine precursors i needed which led me to the search where I found that it was not a dopamine agonist.

That said, I like what it does a lot.

lawson415,

Do you have a specific brand of mucuna that you prefer? I’ve tried NOW Brand “Dopa Mucuna”, but it upsets my digestive system. And, do you find that mucuna works better with food or on an empty stomach?

As for modafinil it is helpful when I need to stay on task (physical or mental) for a few hours, but it usually gives me a modafinil hangover a few hours after taking which I suspect is the beginning of dopamine depletion. So, I only use it if necessary early in the morning. I usually take only 50 mg to reduce the bad side effects. How do you manage to get to sleep if you take 100 mg at noon? If you have any thoughts about these questions I’ll be glad to hear them. But, I understand if you don’t have the time.

Thanks.

We got the MAOa SNPs from reanalyzing the raw genetic data from 23andMe. Over the years, I’ve used Genetic Genie which is the easiest , Nutracker, and Prometheus to re-analyze 23andMe data.

It may be possible to measure neurotransmitter levels from cerebral spinal fluid. There are alternative docs who believe you can tell about neurotransmitters from testing their levels in urine but I suspect that says more about the kidneys than about the nervous system.

I shared an office with a naturopath for a while and she ordered the cortisol test. We learned about the diurnal cortisol from doing a saliva test four times a day waking up, noon dinner time and bedtime. Salivary cortisol tests are used for psychophysiology research as well as clinically.

These tests showed I had low cortisol early in the morning and it didn’t become normal until close to bedtime, which may be why I stayed up late for a lot of my life.

I started doing dopamine agonists because I got hired to measure brain waves associated with taking tyrosine.

It was a pilot study so I figured I would participate just to get a larger sample size. And the dopamine agonist made me feel great. When I re-analyzed the 23andMe data and found out about my overactive homozygous MAOa, I understood why I liked tyrosine and mucuna so much.

Because of this overactive MAOa, I break down dopamine very fast. The references in Prometheus said this SNP is associated with chronic depression and that makes sense because if I don’t take my dopamine precursors, I can’t get out of my own way.

I suspect I can take such a high dose of tyrosine and mucuna because of the overactive MAOa. People without the overactive dopamine oxidation system I have would probably get very anxious with these levels of dopamine Agonist.

And I suspect I don’t crash from taking modafinil because I’m taking so much tyrosine. I do dopamine and mucuna both because the L DopA in mucuna only takes one step to become dopamine. There are more steps to convert tyrosine.

Deprenyl? I’ve been taking it since grad school in the early 90s.

It’s also a neuroprotectorant. There was a documentary about catatonic addicts about 35 years ago. I think it was part of the Nova series. The addicts had been using synthetic heroin and the fella making it let it get a little bit too hot and. made MPTP, a neurotoxin that quickly destroys the substantia nigra. The documentary discussed the Swiss chemist who discovered MPTP and had destroyed his own substantia nigra and had been catatonic in a mental hospital for decades and he was quickly brought back with L dopa.

The chemist reported remembering hearing and seeing everything that happened in his room during all this time.

Deprenyl has been known to protect from neurotoxins for a long time. This is part of why I started taking it. Here is a study from 20 years ago. There are also studies from this year looking at the mechanism of this protection.

“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.”

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Thank you @Vulcan , appreciated

I’ve been taking seligeline since the 90s. It was a big smart drug back in those days. I just Googled seligiline central nervous system inflammation. Here’s a great article I found that suggests part of the neuroproductive aspect of seligiline comes from reducing inflammation in the central nervous system.

“In this study, we aimed to investigate whether selegiline has a protective capacity in the impairment of the BBB in both in vivo and in vitro experiments. In a sepsis mouse model, administration of selegiline ameliorated lipopolysaccharide (LPS)–induced impairment of BBB integrity. Additionally, treatment with selegiline increased the expression of the tight junction protein junctional adhesion molecule A (JAM-A) against LPS. Also, we found that selegiline inhibited the production of the proinflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-1β. In an in vitro experimental model, bEnd.3 brain endothelial cells were exposed to LPS. Results indicate that stimulation with LPS significantly increased the permeability of bEnd.3 cells and reduced the expression of JAM-A, both of which were rescued by treatment with selegiline. Additionally, selegiline prevented the activation of the NF-κB/MLCK/p-MLC signaling pathway in LPS-challenged bEnd.3 cells. These results indicate that selegiline exerted a protective effect on BBB dysfunction, which might be attributed to the inhibition of the NF-κB/MLCK/p-MLC signaling pathway. These findings provide a basis for further research into the neuroprotective mechanism of selegiline.”

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Excellent Vulcan! I’m revisiting this after my gluten fiasco earlier this year. So far for just a few days it’s going much better. It definitely seems good for my marriage.

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What is something that raises dopamine? (supplement or medication?)

Lucky man, I like this, especially coming from a woman :smile: !

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Tyrosine is a precursor for dopamine.
Mucuna puriens is too. It has L Dopa and works fast. Tyrosine is slower to come on but lasts longer.

I have homozygous overactive MAOa SNPS that quickly break down the dopamine. I make. Apparently, these SNPs are associated with long-term depression. My sweetheart has the underactive MAOa SNPS so she cannot break down dopamine very well. When she was prescribed ropinirole for a restless leg, she got so anxious, she became agoraphobic and couldn’t leave the house.

If you’ve got 23andMe or other kinds of genetic analysis that can help figure out which pathways are broken and help choose appropriate supplements.

I take modafinil 100 mg am and noon. I’m actually a perfect candidate this med because i need naps everyday and that’s what is designed for- daytime sleepiness This raises dopamine in the sleep wake cners, focus and cheerfulness. It does not raise dopamine generally which can be unpleasant…

Now brand mucuna is standardized to 15% L dopa son cap is 60mg l dopa. I take one cap am and ohe at noon

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This is where we really need an AI that can parse our genetic data and suggest supplements and medications based on our specific genetic makeup.

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Anyone have opinions on weekly selegiline dosing? Since MAO-B activity takes 2 weeks to get back to baseline after a 10mg dose I don’t see the need to take it daily like you would if treating parkinson’s.

Any issues with sleep taking Modafinil in the afternoon?

I take 200 mg of modafinil when I get up and then I have a 100 mg at noon. I don’t have any problems sleeping. But I do have problems staying awake so I actually use modafinil as indicated. I also take a lot of tyrosine which is a dopamine Agonist so when I get up and at noon. I also take a little bit of macuna which is a faster dopamine agonist at the same times.

I have overactive MAOa Snps which breakdown dopamine is fast as I can make it. If I don’t take the agonists and modafinil, I walk around in a haze.

So the things I do to have a normal amount of neurotransmitters will probably make way too many for people with normal neurotransmitter genetics.

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I take 5 mg of selegilene every morning and I’ve been doing that for over 20 years. I started taking it when it was believed to be a dopamine agonist. And I’ve continued because it’s sort of acts like a dopamine agonist as it is an antagonist for subcortical GABA. A friend gave me a popular ant-aging book about in the 90’s which got me to read the science about it.

My history of toxic exposure made me even more interested.

It protects the brain from MPTP and other neurotoxicants which damage the substantial nigra. Enough of it can destroy the substantial nigra and give you Parkinson’s overnight. Many people got exposed to it in the '80s from a bad batch of synthetic heroin.

MPTP can also take out the substantiania nigra gradually gradually from pesticides. It is a byproduct of the manufacturing and considered an ingredient. I don’t know if the government has forced the pharmaceutical companies to remove that or not. There’s an interesting documentary on NOVA from the '80s called The Case of the Frozen addict that helped us learn a lot about the relationship between neurotoxicants and the substantial nigra Parkinson’s and dopamine.

An interesting review
https://sci-hub.se/10.1038/mp.2016.127

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Where do you get it from. Do you have a prescription?

How did you find out? What dna analysis tool did you use?

No sleep problems. 200 mg very earlynmorning an 100 mg at noon. Bed time around 9:00 Pm

I have a prescription. My primary care provider is a goddess.

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I used 23andme raw data. I have used GeneticGenie, Nutrahack, and Promethiease. 23andme analyzies about 15% of the genome. have an Dante labs kit that does 100% I will send back soon.

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