39 replies to this topic

[gamesguru]

then why should it have supporting studies in the treatment of hyperglutamatergic schizophrenia? theanine more than anything is a modulator.. if you're low it raises you, if you're high it drops you down a notch. curcumin and egcg both inhibit glutamate release, but egcg does so on the presynaptic side and so its extended use may induce a more neurotic state than does a bowl curried lentils

[PeaceAndProsperity]

 

Acetyl-cysteine

l-theanine

fasoracetam

I've read l-theanine can increase glutamate sensitivity in people with excess glutamate

 

It seems so but it's a weird relationship. I almost certainly have a defect of the gene that breaks down glutamate to gaba (normal, cause of autistic rage fits) which causes me to become very enraged and restless if I eat anything with too much gelantin, take too much l-glutamine, drink caffeine, etc.

 

If I have eaten gummy bears (which enrages me more than anything) then l-theanine doesn't seem to worsen or improve it, though creatine works almost instantly to remove the rage (because it competes with glutamate for uptake), which is funny since l-theanine is touted as decreasing glutamate.

However, if I take a high dose of l-theanine then I tend to get symptoms of high serotonin like irritability, fatigue, etc., and the symptoms of high serotonin are in turn almost certainly caused by overactivity of the nmda receptor (since all other agonists do the same).

 

A very low dose, like under 50mg(?), doesn't seem to cause any issues for the most part, but instead seems to help with all sorts of issues.

 

Interestingly, I recently found out that gaba-a agonists (or so it seems) worsen my pseudohallucinations while nmda agonists (not all) tend to remove them 99%, though l-theanine for a short while after taking it can also worsen my pseudohallucinations (conversion to gaba?) whereas a few minutes after worsening them it can do the opposite and improve them. But sometimes it does the one thing and other times it does the opposite.

 

It's a weird supplement.

 

 

[ServousNystem]

Puerh tea, a possible Mglur5 inhibitor?

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5533841/

 

 

 

Pu-erh Tea Inhibited the Expression of mGluR5:

 

 

 

To further validate the inhibition of the expression of the mGluR5, several concentrations of pu-erh tea, 50 μM CHPG (a selective mGluR5 agonist) and 50 μM MPEP (a selective mGluR5 antagonist) were added to SH-SY5Y cells and followed by incubation for 12 h. There were no effects on the growth of SH-SY5Y at the concentration of 62.5 μg/mL (Fig. ​(Fig.3c).3c). The expression of mGluR5 was markedly reduced compared to the control when cells were treated with 62.5 μg/mL of pu-erh tea for 12 h compared to the control (Fig. ​(Fig.5a,5a, b). When SH-SY5Y cells were treated with 62.5 μg/mL of pu-erh tea for various times, pu-erh tea markedly inhibited the expression of mGluR5 compared to the control (Fig. ​(Fig.5d,5d, e). Compared to black and green teas, treatment with pu-erh tea for 12 h significantly inhibited the expression of mGluR5 (Fig. ​(Fig.5g,5g, h).

 

 

Effects of Pu-erh Tea on Neuronal Injury:

 

 

 

Increase in extracellular levels of glutamate leads to activation of mGluR5 and a strong excitatory neurotoxicity, resulting in neuronal swelling and necrosis. To confirm that pu-erh tea protects cells from nerve injury, SH-SY5Y cells were incubated with pu-erh tea before treatment with L-glutamate (L-Glu). The nuclear morphology of SH-SY5Y cells was examined after staining with Hoechst 33342. Compared to black and green teas, 12-h treatment with 62.5 μg/mL of pu-erh tea reduced the number of hallmarks of apoptosis induced by 160 mM L-Glu, whereas the mGluR5 agonist CHPG increased and the mGluR5 antagonist MPEP decreased the number of apoptosis (Fig. ​(Fig.66a).

 

Pu-erh Tea Prevents Epilepsy by Inhibiting mGluR5:

 

 

 

IP3 and DAG, as second messengers, play important roles on in intracellular messenger transduction. These two substances stimulate neurons and can cause neuronal damage if present in excess. We accordingly assayed the contents of IP3 and DAG in the hippocampus by ELISA to confirm the effect of pu-erh tea on prevention of epilepsy. The results showed that IP3 and DAG were increased in epilepsy and decreased under intragastric administration of pu-erh tea (Fig. ​(Fig.7a,7a, b). Histological images using HE staining showed that after epilepsy rat hippocampus showed injury, whereas before intragastric administration of pu-erh tea or diazepam, rat hippocampus showed no changes compared to the control 

 

 

In this study, we discovered that pu-erh tea downregulated the transcription and translation of mGluR5 by Affymetrix Expression microarrays experiments and Western blot. Pu-erh tea also protected SH-SY5Y cells against apoptosis induced by L-glutamate (L-Glu) and alleviated epilepsy behaviour by inhibiting the expression of mGluR5. The results identified mGluR5 as a target for the treatment of neurological and psychiatric disorders and suggested that pu-erh tea might be a potential natural source of protection against neurodegenerative diseases associated with mGluR5. Accordingly, the aim of this study was to identify the protective mechanisms of pu-erh tea against injury to neuronal cells in vitro and in vivo.

 

 

[PeaceAndProsperity]

Puerh tea, a possible Mglur5 inhibitor?

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5533841/

Pu-erh Tea Inhibited the Expression of mGluR5:

Effects of Pu-erh Tea on Neuronal Injury:

Pu-erh Tea Prevents Epilepsy by Inhibiting mGluR5:

I had no idea that mglur5 induced rage could potentially also be connected to neurodegeneration.. that's scary to think about

[Galaxyshock]

Valeriana:

https://www.ncbi.nlm...pubmed/22923195

[John250]

So in conclusion with the best stack for activating Camp be
Forskolin
Artichoke extract
Suma
Jiaogulan
NAC
Theanine

[Furniture]

So to summarize the responses here, these are the compounds, nootropics, & herbs with some evidence to show they interact with mGluRs:

 

Acetyl-Carnitine
NAC 


Suma Root/Brazilian Ginseng


Fasoracetam
Theanine
Nicotine
Nefiracetam
Sarcosine
Pu-erh Tea


Icariin

 

Let me know if I missed any!

Edited by Furniture, 17 November 2023 - 09:52 PM.

[Furniture]

If anyone is interested, I created another thread specifically for approved medications that antagonize (or negatively modulate) mGluR5 and mGluR1. This current thread was asking a much broader question (that is, asking for any compounds whether medications, supplements, nootropics, or herbs that affect any of the metabotropic glutamate receptors). However, I've become much more interested in approved medications that antagonize mGluR5 and/or mGluR1 specifically. The only one I've found so far that is approved for clinical use is Acamprosate (Campral). See new thread for evidence:

 

https://www.longecit...e-campral-does/

 

Basimglurant (a selective negative allosteric modulator of mGluR5) is currently in Phase 2 of drug trials for Pain associated with TN (Trigeminal Neuralgia) & Seizures in TSC (Tuberous Sclerosis Complex) by the pharmaceutical company Noema Pharma.

 

https://noemapharma.com/pipeline/

 

Basimglurant has also recently (about a year ago) received Fast-Track Designation from the FDA:

 

https://www.empr.com...inal-neuralgia/

 

So, we may see it available in the next year or so

 

 

(Also, I was the original poster of this topic, but for some reason all of the content associated with my account has been moved into a dead Guest account called "Guest_Funiture2_*". I have no idea why)

Edited by Furniture, 17 November 2023 - 09:56 PM.