6 replies to this topic

[Mind_Paralysis]

So, I've been researching the relationship between Kynurenic Acid (KYNA) and L-Tryptophan, as well as the NMDA-antagonistic effects of KYNA.

 

My interest began as I have a hypothesis that a majority of ADHD -sufferers appear to have an overly active NMDA-network, which would account for the many secondary diagnoses that we have - such as DCD, Dyscalculia, MDD, etc.

 

My hypothesis was boosted by the growing section of ADHD-ers that see relief from Memantine - a non-competitive NMDA-antagonist - as well as from my initial foray into Schizophrenia -research, where I found many of the biological characteristics of Schizophrenia to be INVERTED from ADHD -

 

• High Dopamine
• Low NMDA activity
• High KYNA

And lo' and behold... when I researched the same mechanisms among ADHD -ers, a seeming pattern emerged! There really does seem to be something to this, since it ties together so many things, quite neatly.

 

• Memantine alleviates ADHD ( Nitromemantine is believed to be even better)
• Ketogenic diet alleviates ADHD for some patients
• ADHD -ers have lower levels of KYNA than neurotypicals
• ADHD -ers have lower levels of L-Tryptophan than neurotypicals
• Circadian rhytm dysfunction is a common ADHD symptom, and Melatonin is synthesized from L-tryptophan

This gives me the hunch that inhibition of the NMDA -network is essential for treating ADHD, and the reason why is because we have some kind of problem with our L-tryptophan processing, as KYNA is produced from Tryptophan.

 

As such:

 

Tryptophan -> KYNA

                   -> Melatonin

                   -> 5-HTP -> Serotonin

 

Now... what do you fellas reckon' about this hypothesis? How does one go about increasing KYNA, WITHOUT increasing Serotonin? My main idea at the moment was to utilize a combo of L-tryptophan supplementation with Tianeptine - so as to clear out Serotonin, while still receiving higher KYNA -production, and possibly receiving even more NMDA -antagonism from the potential NMDA -interaction of Tianeptine! ^^

However, turns out Tianeptine probably doesn't truly increase Serotonin reuptake... So, there goes another great idea in the trash-can.

 

 

So, any ideas lads? How do I increase my KYNA -production, while at the same time NOT increasing Serotonin-production?

 

 

 

 

Here is a list of the articles which inspired this hypothesis:

-------------------------------------------------------------------------------

Ketogenic diet increases concentrations of kynurenic acid in discrete brain structures of young and adult rats - Springer

 

Brains of Children with ADHD Show Protein Deficiency | Psych Central

 

Inhibitors of kynurenine hydroxylase and kynureninase increase cerebral formation of kynurenate and have sedative and anticonvulsant activities. - PubMed - NCBI

 

Behavioral and Brain Functions | Full text | Attention-deficit hyperactivity disorder (ADHD) and glial integrity: S100B, cytokines and kynurenine metabolism - effects

of medication

 

 

[Mind_Paralysis]

I've actually found a way to do this now - Nicotinylalanine increases the levels of KYNA in the CNS, to a greater degree than regular supplementation, such as with Tryptophan. I also realized that unless you're also using an SSRI as well, then the production of 5-Htp from Tryptophan is obviously rate-limited, so no need to worry about lowering Serotonin.

 

Only problem is of course that Nicotinylalanine seems to be untested on humans, nor is there any info on whether it can cross the blood-brain barrier when taken orally. The tests where with cateters straight into the brains of rats...

 

However, Dr. Roberto Pelliciari of the Pellicari-group has an old patent for the use of Nicotinylalanine in treatment of CNS -disorders, so I am going to try and get a hold of him, and see if he has more information he is willing to share on the subject, as well as perhaps some look into my hypothesis. He seems to be something of an authority of the Kynurenin-pathway.

 

http://www.efmc.info...-2010-3/lab.php

 

Now, I see that I got an ill-informed tag, and since the previous entry was somewhat ill informed, then I suppose that's justified - but I would rather appreciate an explanation when given such a tag, as I have no idea where I have failed if I AM ill-informed, now do I?

I seek knowledge, and if you see someone posting something incorrect, then I think it's just best for everyone if that person is then given correct information instead, so as to not spread more misinformation, or simply to educate the person at hand, out of kindness and passion for the sciences.

 

 

Reference:

----------------

Nicotinylalanine increases the formation of kynurenic acid in the brain and antagonizes convulsions. - PubMed - NCBI

Edited by Stinkorninjor, 08 April 2015 - 12:57 AM.

[Blackkzeus]

In what type of ADHD population does Memantine alleviate symptoms? Hyperactive or inattentive?

[xks201]

Might be onto something.
Saw a couple studied implicating b6 deficiency In this. My nutri eval shows low kyurenic to quin rati.

[Mind_Paralysis]

In what type of ADHD population does Memantine alleviate symptoms? Hyperactive or inattentive?

Both, it would appear. It enhances memory and lowers medication-threshold dramatically. The reports tell of a dramatic increase in clarity and even some enhancement of executive function - something that regular ADHD-medications have yet failed to enhance.

 

That's one of the reasons I started looking into the NMDA-network in ADHD-individuals - and lo' and behold... there seems to be something seriously wrong here.

 

 

Might be onto something.
Saw a couple studied implicating b6 deficiency In this. My nutri eval shows low kyurenic to quin rati.

 

Well, if the hypothesis is correct, that ADHD-ers have malfunctioning Tryptophan metabolism, or KYNA -synthesis, then that definitely makes sense.

[Blackkzeus]

How has memantine affected you?

[Mind_Paralysis]

How has memantine affected you?

 

I sadly haven't tried Memantine - however, it should definitely be mentioned that the dose-titration and the dosing-scheduling of Memantine is extremely important - the slightest mishap there, and you will get immediate brain-fog. That's no doubt why the drug has so mixed reports when it comes to treating ADHD.

 

For a big, big thread with various reports on the effects of Memantine on ADHD, check out this thread over at ADDforums:

 

http://www.addforums...ead.php?t=80317

 

 

 

You can read up a bit more on the actual studied effects of Memantine on ADHD in these studies:

 

Memantine for Executive Dysfunction in Adults With ADHD: A Pilot Study

https://clinicaltria...lts/NCT01533493

 

Memantine in the Treatment of Executive Function Deficits in Adults With ADHD: A Pilot-Randomized Double-Blind Controlled Clinical Trial.

http://www.ncbi.nlm....pubmed/24970718

 

Memantine: A Review of Possible Uses in Child and Adolescent Psychiatry

http://www.ncbi.nlm....les/PMC3647634/
 

A pilot open label prospective study of memantine monotherapy in adults with ADHD.

http://www.ncbi.nlm....pubmed/22436083

 

 

The efficiency and dosing-problems of Memantine are definite factors that started my research into the NMDA-network in ADHD - my look into KYNA is an attempt at finding a possible alternative to Memantine, as it clearly has its drawbacks.

However, it should be noted, NITROmemantine is a drug which has even greater NMDA-antagonistic properties than Memantine, and the initial reports indicate a far, far greater efficiency in treating neuropsychiatric conditions with the Nitro-variant. However, it's super-new, and not even on the market yet.

 

However, it might actually be a better mode of approach, since increasing KYNA globally might not be an ideal approach - I was advised recently by our very own GetOutofBox ( a legendary user at this forum) how this might not be ideal, since in reality, it could give rise to immediate severe side-effects that could impair cognition - it's the same old problem with non-selective drugs - it's the reason why SSRI's where developed, and why Methylphenidate gives some damn many side-effects - raising the level of a chemical globally, just isn't a good idea.

 

The future of pharmacology is ONE BULLET - ONE KILL. ; )