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.”
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.
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
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.
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.
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.
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.
Just a reminder about dosage as discussed earlier:
The Life Extension Foundation (LEF) recommends daily dosing totaling 10 mg per week.
Researcher Joseph Knoll recommended 1 mg per day.
This is for Deprenyl that is swallowed and not taken sublingually.
Deprenyl was found to work synergistically with Polyscias Fruticosa in mice and rats to extend lifespan. Polyscias fruticosa is available as loose leaf tea.
I remove larger stem pieces and then pack one of these tea infusers.
First, like rapamycin for longevity, neutrigenomics is also relatively new and still at the pre-scientific stage.
I’m returning to this thread after some time. I was asked where I found out about the SNPs. I got them from re-analysis of 23andMe raw data. 23andMe only analyzes about 15% of the genome so I wouldn’t recommend them. I’ve got a kit ordered from Dante. Periodically they have a $199 full genome analysis sales.
With the full genome, there will be a lot of problematic SNPs. The re-analysis programs will alert you to problem mutations.
Promethiase should have all the problematic mutations. I’m going to say mutations because my Android dictation does better with that word then using the acronym. It seems to be compiled for professionals so it can go into more detail than then I can understand. On the other hand, it won’t go into enough detail for us to understand if we’re not well educated in molecular biology. And maybe evolutionary biology too.
A previous post listed the reanalysis services that I used.
I found this website when we got started 10 or 12 years ago. It’s a great overview and it’s been extended quite a bit since last time I looked at it. It is from a for-profit medical practice so you’re not going to get the best deal on supplements from them. That said, they’ve been doing neutrogenomics for a long time and might be helpful.
There is a big learning curve, even for a professionals, so if you can find somebody with a lot of experience and you have money, it might be faster to work with a person like that then hacking it yourself. The hacking is fun but it can be slow and there may be some uncomfortable mistakes. It might depend upon how young you are and how much time you have.
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