NMDAR blocker that might help ?

[Labyrinth]

Hello Guys
i am pois member since long time
unfortunately about 6 yrs ago i was hit by neuronal excitotoxicity cause by pois , coffee abise and continous inflammation
since then i have a focus in brain working automatically by it self . it does not stop . always ringing   

can u pls guid me to which NMDAR blocker that will help me control this focus
NMDAR blocker can be a supplement or a drug have no problem with that and thanks alot

[Scrub]

Have you tried memantine?

[Labyrinth]

Have you tried memantine?

No does it work in pois ?!

does it relieve the neuropathy

[Scrub]

Have you tried memantine?

No does it work in pois ?!

does it relieve the neuropathy

I don't know if it works or not for POIS prevention, I wanted to try it but instead tried with pyridostigmine having huge success. i'm pretty much sure memantine is an NMDA antagonist used to prevent glutamate exitotoxicity for dementia and alzheimer disease.

You could try and see if it works, can't remember if anyone has tried it here before.

[Quantum]

Hello Guys
i am pois member since long time
unfortunately about 6 yrs ago i was hit by neuronal excitotoxicity cause by pois , coffee abise and continous inflammation
since then i have a focus in brain working automatically by it self . it does not stop . always ringing   

can u pls guid me to which NMDAR blocker that will help me control this focus
NMDAR blocker can be a supplement or a drug have no problem with that and thanks alot

Hi Labyrinth,

In my pre-pack, that does prevent POIS for me, there are 4 different NMDARs blockers, of natural origin:  Green tea extract, magnesium, flaxseed oil, and L-Theanine.   

L-Theanine is found in green tea extract, for sure, but I take a capsule of both in my pre-pack ( one of green tea extract, one of L-Theanine).

For preventing excitotoxicity, I do think that adding IDO inhibitors like rosemary and curcumin, and TDO inhibitors like milk thistle and quercetine, is very useful as well.

[b_jim]

I really think these NDMA receptors must be the key of Pois.
But why these receptors are activated by orgasm/ejaculation ?

Anyway :
Magnesium helps my Pois and it's 100% sure my magnesium deficiency came slowly at 13/14/15 years old exaclty in the same time that my Pois.
Magnesium decreases NMDA activity. My premature ejaculation probelems and anxiety came in the same time.

Sugar increased my Pois symptoms, increases my muscular tremors. Muscular tremors are much stronger after ejaculation. Sugar gave me diarrehas epecially 3/4 hours after ejaculation and I often said "my Pois startd in my intestine". Sugar activate NMDA receptor and I posted a scientific article showing low carb diet is effective againsts seizures.

Taurine clearly blocks my Pois symptoms and seems to have effect on NMDA.

 
Clearly,influcencing NMDA is my target for 2018. Another amino acid important for NMDA activity is glycine which is very important for NMDA.

[nanna1]

  I just wanted to suggest some ways to hack the NMDA/GABA-A/Glycine receptors. Hopeful this will spark some discussion and testing around two supplements that have not been discussed on this forum yet. I know that the GABA-A and the Glycine receptors are chlorine dependent receptors. When stimulated, they pump chlorine ions into neurons to counter NMDA signaling.

Also, like b_jim mentioned earlier, magnesium ions block the NR1-NMDA receptor.
 
  So magnesium chloride seems like it could enhance GABA-A and Glycine receptor signaling by supplying chlorine, while also inhibiting NR1-NMDA receptor by supplying magnesium. Also, because magnesium chloride is an extremely small (two-atom) molecule, its bioavailability is high due to passive diffusion (Ref1, Ref2, Ref3). However, magnesium gluconate has the highest bioavailability (Ref4). As a oral supplement 2g taken twice a day should be enough but it has to be mixed with water or juice (water soluble). From what I hear, it has a bad taste due to the chlorine, so a few drops of lemon juice can improve the taste. You can also soak with therapeutic-grade magnesium chloride in your bath water to relieve neurological pain throughout your body.

"The efficacy of beta-alanine at the GABAA receptor is comparable to that of GABA. Similarly, the efficacy of beta-alanine at the glycine receptor is comparable to that of glycine." -Dual activation of GABAA and glycine receptors by beta-alanine: inverse modulation by progesterone and 5 alpha-pregnan-3 alpha-ol-20-one.

  A second hack of the NMDA/GABA-A/Glycine receptors may be beta-alanine. I mix beta-alanine (BAL) in my pre-workout protein shake, so I know first-hand that this works to calm nerves. The effect is very noticeable partly because BAL causes a tingling effect that feels similar to niacin-flush. In a comparative study of BAL, glycine, GABA and taurine, beta-alanine was shown to be as effective as glycine and GABA at stimulating the Glycine/GABA-A receptors (Ref).

Measurement of chlorine currents

  In this study, glycine was the most potent agonist of the Glycine recepor. However, since glycine does not stimulate the GABA-A receptor, beta-alanine is more potent than glycine at GABA-A receptor signaling.
  GABA was the most potent agonist of the GABA-A recepor. But, since GABA does not stimulate the Glycine receptor, beta-alanine is more potent than GABA at Glycine receptor signaling. Also GABA does not cross the blood brain barrier, whereas beta-alanine does penetrate the BBB. So beta-alanine supplementation is more GABAergic than GABA in vivo. 2g of beta-alanine per serving should be enough.
  In the presence of glutamate, glycine can stimulate the NR1-NMDA receptor and cause neuron excitotoxicity (Ref5, Ref6).

NMDA receptor

Receptor signalling:

• GABA (GABA-A, GABA-B receptors)
• glycine (Glycine receptor, NR1-NMDA receptor, causes glutamate-NMDA excitotoxicity)
• taurine (GABA-A, Glycine receptors)
• beta-alanine (GABA-A and Glycine receptors)
• magnesium chloride (inhibit NR1-NMDA receptor, provide chlorine ions for GABA-A and Glycine receptors)

  I just wanted to bring this up because, I have not seen anybody discuss magnesium chloride or beta-alanine.

[b_jim]

Thanks for this brilliant post.
I would like to try biglycenate magnesium but it seems you don't recommand it.
I tought glycine works like magnesium and then inhibits glutamate activity.


I wonder if salt may help too. When I work too much I have more tremors maybe I lost salt by perspiration.

[Quantum]

Hi Nanna and b_jim,

As you are aware of, I am using NMDAr blockers in my pre-pack against POIS, and also using it post-E whenever needed.  NMDAr blockers are beneficial for me in POIS ( not alone, but an important part of my method of control).

Magnesium, historically, has been the first supplement I have found to have some relief to my POIS.   I have tried a lot of Mg preparations, many salts  ( the one I am using right now, the Jamieson brand, is a blend of many natural Mg salts).   I have used magnesium chloride as well, but it causes more diarrhea/loose stools problems, for me.   It is more useful, in my case, to take my usual Mg supplement, along with salted water ( note: table salt is sodium chloride, so it supplies chlorine, and also, sodium, which is good for me, since POIS causes me hypotension +++, and sodium raises blood pressure).   I have tried sodium bisglycinate as well, but my preferred form of magnesium is still the Jamieson specific blend of natural Mg salts.

I never tried beta-alanine  ( not sure I want to boost dopamine levels, and beta-alanine does).   Here are some notes about beta-alanine, that could especially worthy if used with taurine:

"Beta-alanine moderates many neurological actions through competitive inhibition of taurine (beta-alanine and taurine compete for the same transporter to get into the brain).[81][82] This is why cells incubated with beta-analine see their taurine stores depleted, either in part[83] or in full.[84]

Beta-alanine appears to act via glycine and GABAA receptors (like taurine[85]) with comparable efficacy to glycine and GABA themselves.[86] On the other hand, beta-alanine has been noted to act as an antagonist of the system A transporter, used by cells in the brain to take up glycine.[87]

 Beta-alanine may have effects similar to the inhibitory neurotransmitters glycine and GABA, while at the same time competing with these molecules. The overall consequences are unclear at this time." ( https://examine.com/supplements/beta-alanine/#summary4 )

[Quantum]

Here is a list of NMDAr blockers I have been using or have been considering to use:

- Magnesium  (binding site in center channel)  :  in tablets ( different salts),  Mg cream, cream with epsom salt  (5g  of epsom salt deliver 1g of mg – 20% mg in espsom salt, which is magnesium sulfate ) or use of epsom salt in bath.

- Lignan (in flax seed oil)

- L-théanine : structure similar to glutamate – binds at glutamate binding site, but without the toxic effect of glutamate (antagonist of the following Glutamate receptors: AMPA, Kainate, and NMDA)

- Zinc

- Acetyl-L-carnitine

- Taurine (possibly an allosteric modulator)

- Cat's claw (Uncaria tomentosa)

- Ibuprofen  ( protects from glutamate toxicity)

- Huperzine A 

- Dextrometorphan

- garlic ( S-Allylcysteine )

- Guiafenesine (possibly)

- Ethanol ( alcohol), but has also neurotoxic effect in counterpart, so not very useful.

- CoQ10

- creatine ( http://www.ncbi.nlm.nih.gov/pubmed/22347384 )


Some NMDAr blockers that I would not use ( because too much side effects, or on prescription only, or simply too dangerous):

Ketamine :  far too dangerous for the brain ( dissociative)
AV-101  ,  in development, by VistaGen( glycine binding site)
Polyamine (Spermine and spermidine - Mg binding site?)
Agmantine ( polyamine site)   Toxic in higher dosage, so not safe to use
Minocycline: prescription antibiotic, so not a good choice for long term use

--
 

From this list, those I chose and still using regularly in my pre-pack are magnesium, lignan ( flaxseed oil), and L-theanine, in an effort to combine NMDAr blockers acting at different sites on the receptor, and that are quite safe in long term use.

I also use taurine, but have it in bulk powder, so not as handy for my including in my pre-pack.

[b_jim]

Fantastic list, fantastic job !
I'm convinced the key of Pois is here because some of these elements influence my Pois.

[Hopeoneday]

This Franch guy is helped this-
http://poiscenter.com/forums/index.php?topic=2670.msg24327#msg24327
Yours opinions-what ingredient from this suplement get rid pois from him by 99%?

[b_jim]

I don't know if his post is linked with what we are talking about, maybe not.

Do not know why is this hapening(myabe thouse food bring energy in cells-some metabolic isue) , lemon kill some bugs in stomach, or lemon flush (increase my bile fluids) , or it is sugeer insulin isues(insulin sugar on celular level).

I often imagine taurine increase my bile and helps to keep testosterone homeostasis supposed to up and down after ejaculation.

[b_jim]

I can give a new element 100% sure :

Something happens with chlorid. Chlorid blocks fasciculation/muscle tremors symptom out of pois.

After hard working out, I always have lot of muscle tremors and even short depression when my body is exhausted. i take lot of magnesium but it's not enough. Adding salt in my water and food block this symptoms.

Why I think chlorid is the culprit and not sodium ? Because sodium bicarbonate seems not to give the same effect.

What about this in Pois ? Electrolytes unbalance  is something to look for.

[dizzy]

I recently had some brief success with MgCl2, but I was also taking other stuff. I'm now trying to get the effect back.

[Muon]

After hard working out, I always have lot of muscle tremors and even short depression when my body is exhausted. Adding salt in my water and food block this symptoms.

I have the same. Exercise, heat, POIS leads to fasciculations.

Why I think chlorid is the culprit and not sodium ? Because sodium bicarbonate seems not to give the same effect.

Have you tried KCl salt and compared that to sodium bicarbonate?

What about this in Pois ? Electrolytes unbalance  is something to look for.

It sounds to me like there is a change in ion flux through voltage-gated ion channels after POIS. POIS -> release of unkown particles -> particles get temporarily stuck in these channels or perhaps auto-antibodies blocking these channels? Someone should look up if mast cell mediators can affect these channels in a way.

[b_jim]

No, I didn't try KCl.

 I tried NaHCO3 (sodium bicarbonate for my gastritis) which seems not to improve muscle tremors (need more test to be sure).

But normal salt (NaCl) seems to work ! So the difference is chlorid element.

I suspect electrolyte unbalance after ejaculation inside the intestine and maybe on NMDA receptor explaining lot of things.
Sugar gives me diarreha all the time and especially in Pois. Sugar is suspected to cause electrolytte unblance too.

My knowledge about NMDA receptor is poor, I need to learn more and thanks for details given on previous page.

Maybe KCl is a good combo because K is an important for electrolytes balance and natremic balance.
Maybe Mgcl is another good combo.

Thanks.

 

[Quantum]

I can give a new element 100% sure :

Something happens with chlorid. Chlorid blocks fasciculation/muscle tremors symptom out of pois.

After hard working out, I always have lot of muscle tremors and even short depression when my body is exhausted. i take lot of magnesium but it's not enough. Adding salt in my water and food block this symptoms.

Why I think chlorid is the culprit and not sodium ? Because sodium bicarbonate seems not to give the same effect.

What about this in Pois ? Electrolytes unbalance  is something to look for.

Very clever observation, b_jim


Magnesium, potassium and chloride all help me with POIS, and they all help me after sports too ( I recover with difficulty from sports, in particular when I have sweat a lot, which means I have lost electrolytes through my skin ).

As I have mentioned in my prevention method thread, I have included potassium in my pre-pack.  It is, actually, KCl, potassium chloride, so the benefit may be doubled by the chloride, based on what you say here ( I do not have problem in all body muscles, but particularly in cardiac muscle, it seems)

Also, I need to take potassium chloride after sport, unless I experience a kind of cardiac problem, once the adrenaline goes down.  My heart pounds hardly, as if it struggles to do its pumping work properly, and also beats faster.   20 minutes or so after taking potassium chloride, those symptoms improve or even totally disappear.

[b_jim]

Anyway, I forgot to take my taurine sunday and dispite mg and salt, i had huge fatigue monday and tuesday. 

it's like if taurine is pumped to rebalance something lost after ejaculation. Amazing difference. Tuesday I had at least -50% muscular energy.

[demografx]

Interesting, b_jim!