Commonly Used Antihypertensive Drugs In The Treatment Of Schizophrenia Or Dementia? Let’s Talk About Kynurenic Acid

For many years, decreased dopaminergic neurotransmission along with glutamatergic signaling hypofunction in the prefrontal cortex was the leading explanation for memory impairment observed in patients with schizophrenia. However, current antipsychotic drugs, which affect mainly dopaminergic and serotoninergic neurotransmission, are not fully effective in the treatment of the negative symptoms of schizophrenia. Recently, other factors including disturbance in kynurenic acid (KYNA) biosynthesis, are considered to be involved in schizophrenia pathogenesis.

KYNA is an endogenous substance produced widely in the body, including the brain, where it is synthesized by the kynurenine aminotransferases (KATs). KAT II is the main isoenzyme responsible for brain KYNA synthesis. KYNA is a potent free radical scavenger and an antagonist of ionotropic glutamate receptors, thus it is generally considered as a neuroprotective agent. However, the occurrence of negative symptoms and cognitive decline in schizophrenia was linked with elevated brain levels of KYNA and attenuated glutamatergic neurotransmission in the mesocortical pathway. Thus, it has been hypothesized that suppression of KYNA production may generate an improvement in negative schizophrenia symptoms treatment. This is why KAT II inhibitors are currently being tested as a potential adjunct therapy for memory impairment, especially in schizophrenia patients.

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We were just talking about this yesterday.

It was a post about eating sushi amd then it turned into a talk of getting parasites from sushi.

Last, this one guy i never seen around before brings up your KYNA. Then posted an articale.

Suposedly, people with toxoplasmosis/ toxiplasma Ghondii have lower levels of KYNA. cant remember the whole articale.

Now i gota go look for it.lol

you got good timing

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I posted this earlier.

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sorry - I missed it. I realize now we turned of the warnings/ability to have duplicate titles (because we have so many different topics now - its easy to have the same duplicate titles of posts - so I need to be more careful.

That’s ok, people are more likely to respond to your posts anyway.

and, a few duplicate posts is not a big deal - people might miss one, but read the other.

@SzAdmin @firemonkey Great post. Thanks to you both.

Can anyone give us a TL;DR version- specially if there are any herbal/supplement or Meds that are available that target this area?

Are there KAT inhibitors available or are there all RC’s ?

Just read @firemonkey posts …so here are the current possibilities of using ACE inhibitors to lower KAT II …"Since KYNA is a glutamate receptor antagonist, we analyzed the effect of three ARBs: irbesartan, losartan and telmisartan on KYNA production in rat brain cortex in vitro.”

Possibly amino acids. A number of them reduce KYNA.

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Trying to get my head around this. My quick scan suggests to me that high KYNA producing enzymes levels are associated with brain uptake of KYN. Hence thats bad as there is now less KYN in the brain (its been uptaken) to agonise the NMDA receptor - which is the same receptor that Glysine, Sacrcosine and D-Serine agonise…right?

So shouldnt Glysine and D-Serine be part of that list …I guess not as they do the job directly (agonise the NMDA) rather than inhibit the enzymes that help the reuptake of KYN …which then builds up and does the same thing ( agonise the NMDA)

So it would seem the aminos (prolly need to isolate the most active ones ) along with the anti hypertensive - telmisartan (as research has been done on that ) would be good candidates to cycle on/off with Glycine/Sarcosine/D-Serine so that the NMDA receptors dont get overly sensitized to any one agonist ?

Or stacking them to see if they have culminated effects …
Anyone got telmisartan and Glycine/D-Serine ?

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To keep things simple while experimenting with these I would suggest avoiding in the first instance - phenylaline and tyrosine as tyrosine breaksdown to L-Dopa which go onto make dopamine - which one would want to minimize. Also phenylaline can be metabolized to tyrosine so that wold be similiar.

The “safest” one that pops out to an untrained eye may be cysteine as NAC is currently used as adjunct to AP therapy. I would probably include luecine and isoluecine being BCAA’s I think.

Not sure about the others though Alanine glutamine,glutamate are used extensively in Body building circles so obviously have strong growth effects and may also conflate results. Alanine & Aspartate were quite benign but I tended to get a bit delusional on large doses of glutamine and glutamate - YMMV.

Any thoughts or experience with these ?

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I think it illustrates how much more research needs to be done.

Probably safer to play with various amino acids than many other supplements though.

As for me, I’ve tried whey protien (which contains many amino acids) NAC, and Lysine, and I’ve stuck with the NAC. The others, if they had an effect, it was not particularly noticeable. It didn’t make things any worse though.

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