MAO-B inhibitors, natural sources, how they effect GABA, and neuroprotective potential

I will be culminating relevant information I find on MAO-B inhibitors, natural sources, and how MAO-B inhibitors effect GABA and disease progression. Please, if you have information and sources to share, that would be appreciated. (If my using HU as a means of consolidating this info is excessive posting, I apologize. I learn so much from your contributions. Thank you, researchgate.net/publicatio...

[Hidden]

What is KDS2010?

[Hidden in reply to Hidden]

It’s linked

[Hidden in reply to Hidden]

you should modify the title and mention KDS2010

[Hidden]

A new MAOB inhibitor being researched in Korea. Effects on GABA levels being researched.

researchgate.net/publicatio...

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Axial PD symptoms might not be due only to dopamine but to GABA levels. Although not discussed in this trial, it is my current understanding that MAOB inhibitors decrease the impact or volume of GABA. In human study.

(These comments are my notes. I’m not making claims of knowing anything or advising anyone.)

ncbi.nlm.nih.gov/labs/pmc/a...

[Bolt_Upright in reply to Hidden]

Very interesting. Thanks for posting.

[MarionP in reply to Hidden]

You know what, this GABA and glutamate/glutamine in the three other (non-nigra) regions is damned interesting. Actually fascinating. This could open a whole new avenue of research and maybe illuminate a great deal. Now how to modify them in those structures (and perhaps only those- maoiB may just be a proper start). Very very interesting! It all ties a lot of things together in my mind, including psychiatric crossovers.

[Hidden in reply to MarionP]

Marion, I greatly appreciate your constructive comments, like this one. You are in the unique and coveted position of being equipped with the experience and intellect to unravel this far better than a laymen like myself. I take this very seriously but I’m self aware enough to not take myself too seriously as I’m at least somewhat self aware enough to acknowledge that none of this is my forte.

Yet I’m endeavoring to unravel the complex tangle that is labeled as PD. I humbly ask for you to contribute your knowledge more.

I’m capable of being dry and sarcastic as well (as you know) Can we perhaps endeavor to recognize how although they intent (which we may not want to acknowledge) is to belittle and demean the recipient of our quips, it is really the instigator demeaning and belittling oneself by stooping so low.

Back to glutamine and it’s effect on the brain; is this at all related to the excess of iron and calcium in the PD brain? Could the commonality of excess glutamine, iron and calcium be decreased BBB function which brings us back to the vagus nerve and gut?

I will not be surprised in the least if I’m stating something obvious but I’m truly trying to understand.

[Hidden]

Concise video about what the Korean researchers think is occurring in the Pd brain regarding MAO-B inhibitors and GAMA. (Rescuema shared this excellent video.)

States that current MAO-B inhibitors are only effective short term. Safinamide & KDS2010 have a longer effect.

Can anyone taking Safinamide share their knowledge and experience? Thank you

youtu.be/pRaQosvet6k(Not working as expected?)

[park_bear in reply to Hidden]

Overall Efficacy and Safety of Safinamide in Parkinson's Disease: A Systematic Review and a Meta-analysis

pubmed.ncbi.nlm.nih.gov/336...

"Results: Six studies with a total of 2792 participants were identified. In PDwMF patients, safinamide 100 mg as add-on to levodopa (L-dopa) significantly increased ON-time without troublesome dyskinesia (MD = 0.95 h; 95% CI from 0.41 to 1.49), reduced OFF-time (MD = - 1.06 h; 95% CI from - 1.60 to - 0.51), and improved UPDRS-III (MD = - 2.77; "

[Hidden in reply to park_bear]

Park Bear, could supplements that increase GABA be contributing to the problem and working against MAO inhibitors like Safinamide?

[park_bear in reply to Hidden]

I have not studied this matter so I do not know.

[Hidden]

If GABA astrocytes are contributing to or the cause of dormant dopamine neurons, would reducing or at least not increasing GABA be advisable? Melatonin, L-Theanine, Quercitin, Ashwaganda, etc etc (many I’m finding) all increase GABA.

Could supplements that increase GABA be hurting our dopaminergic neurons long term?

Can some patient researchers please share any info on this and dive in to this research with me?

[Bolt_Upright in reply to Hidden]

As somebody pointed out on this forum some time ago: All of these supplements may do nothing, but if they do something, then that something might be something good or it might be something bad

[Hidden in reply to Bolt_Upright]

In my personal experience, Supplements can most definitely help. Vitamins most definitely can help. I am much improved from how I was a year ago. My father did not know he was getting some new supplements. He showed improvement. They can help. But as with everything, caution and sense is required.

[Hidden in reply to Bolt_Upright]

A Functional Medicine doctor can help advise you on vitamins and supplements specific to your needs. They run extensive blood work.

I enjoy researching but I always discuss my findings with my doctor before implementing anything.

It’s not just an expense. It’s an investment.

Institute for Functional Medicine link below.

ifm.org/

[SilentEchoes in reply to Hidden]

I suspect fentanyl inhibition of GABA made my ALS worse.

[MarionP]

Are you going to share what you find with us? About what natural maoiB exist and whether/how they are effectively administered/delivered (this last bit just as important as the substances themselves). Would be very excellent if you share.

[Hidden in reply to MarionP]

I will do my best Marion. 😊. Thank you for your interest. Many others know far more than me but I do enjoy researching.

[Canddy]

KDS2010 is patented by a Korean Pharmaceutical company NEUROBiOGEN - neurobiogen.com/eng/main/

The compound is listed as SeReMABI (look under "Pipeline"; no clinical trials are listed yet.

Here is another article discussing the potential use of KDS2010 in another indication:

eurekalert.org/news-release...

[Hidden in reply to Canddy]

Hi Canddy! Very interesting. (I know very little about this) but it’s particularly interesting that it’s used for strokes. Because I read L-Serine is also used for strokes to inhibit glutamate. L-serine is being / has been researched for ALS and neurodegenerative diseases. I was not aware of a stroke / PD commonality.

[WinnieThePoo in reply to Canddy]

And should clinical trials start...

[Canddy in reply to WinnieThePoo]

Here is more on a collaborative agreement that was signed (about a year ago) to develop SeReMABI (KDS2010) - we will see....it will be a while for clinical trials to start...

ibs.re.kr/cop/bbs/BBSMSTR_0...

[SilentEchoes]

"Here, we tested the therapeutic potential of KDS2010, a recently synthesized potent, selective, and reversible MAO-B"

This suggests the researchers found a natural source of MAO-B and copied it in the lab so they can patent it. Bioprospecting is the act of seeking out new medicines and commercial compounds from plant and animal species.

Plant compounds have synergy that pharmaceuticals don't.

pubmed.ncbi.nlm.nih.gov/242...

Licorice root has very high MAO-B inhibition.

SE

[Hidden in reply to SilentEchoes]

This is why I like to look at what is being used in trials and pharmaceuticals to try and retrace steps back to the original components or process to see if there is something accessible and likely safer that we can implement now. Which is why I use a little licorice every evening.