A wonder drug for glutamate toxicity?

For everyone who eats free glutamate

I just found this article by James South. I have admired his article on excotoxins for a long time now and feel that he may have MSG intolerant peoples best interests at heart. HE seems to really know his stuff. I know he is also selling these drugs and is therefore in it for more than just curing people - however we all have to make a living.

The supplement in question is Idebenone.

[www.smart-drugs.com]

Idebenone – The free radical quencher

"Idebenone is a powerful antioxidant, more so than CoQ10, and in some studies is 30 to 100 times more effective, than vitamin E or vinpocetine as a free radical quencher within the brain cells.

Idebenone lessens the free radical induced mtDNA damage that accumulates acceleratingly over a lifetime, slowing organ damage and aging.

Glutamic acid and aspartic acid are the two chief excitatory amino acid neurotransmitters in the human brain. Without them we would be "mental vegetables."

Yet under certain conditions, e.g. stroke or traumatic brain injury- excessive amounts of excitatory amino acids accumulate in the fluid surrounding brain cells, causing damage and even death to nerve and glial cells through free radical mechanisms.

Excitatory amino acid toxicity is at least partly responsible for the neurotoxicity of the recreational drug "Ecstasy or MDMA." Studies over the past 30 years have also shown that excessive dietary intake of excitatory amino acids may also damage brain structure/ function, especially in children or excitatory amino acid sensitive adults.

In studies with various types of nerve cell, as well as oligodendroglial cells (which make up the protective myelin sheaths surrounding many nerves, the so-called "white matter" of the brain). Idebenone has shown dramatic protective effects against glutamate toxicity.

Fran

Thank you, Fran. I'll have to look into idebenone.

PC

I think this could keep us busy.

[www.idebenone.org]

Richard

Fran and Richard,

Clearly glutamate is quite damaging from the standpoint of its excitotoxic properties.

However, I believe that dietary MSG and free glutamate cause me problems because they enhance vagal tone. Glutamate is the neurotransmitter for vagal tone. Although the blood brain barrier is impermeable to glutamate, glutamate can diffuse into the hypothalamus and more importantly into the nucleus tractus solitarius (NTS) in the medulla oblongata. This latter structure is circumventricular and is easily accessed by glutamate from the cerebrospinal fluid.

Please see figure 5 at
[webteach.mccs.uky.edu]
for an actual photo demonstrating how close the NTS is to the fourth ventricle.

The NTS is responsible for initiating signals to the nucleus ambiguus (NA) that control HR. This usually operates through stretch receptors in the lung (respiratory sinus arrhythmia), but dietary glutamate should, at least theoretically, be able to stimulate these same vagal motor nerves (NA) to the heart through the NTS.

Whenever I eat seaweed, e.g., sushi, my odds of triggering AF a few hours later are GREATLY increased. My PACs become markedly increased, my HRV increases, and HR decreases. This time frame fits very nicely with the time required for the glutamate to diffuse from the blood into the CSF and into the fourth ventricle and from there to the NTS.

Richard,

Don't apologize for your long post. I'd forgotten about James South's wonderful article on glutamate. I certainly agree with Fran that he appears to know his stuff, even if he may stand to benefit from the sale of idebenone. Also wrt glutamate you might enjoy visiting
[www.bioscience.org]

PC v54

Thank you PC, for those links. I had forgotten that you quit eating sushi, and guess I didn't know that you had the same effects from free glutamate. I thought you were testing the theory out. The plot (pot)thickens, as we add more humans to the glutamate stew.

The second link you gave said this:

The enzyme (glutamate sythetase, I believe is what it's referring to) is irreversibly inhibited by methionine sulfoxamine (MSO) (90). Under 5.1

I read it twice and will reread again, but do you know what this means. As you may have seen in my CR postings, I feel that the sulfur based aminos could help this condition. I'm certainly going to give this a much harder look and brush up on the workings of glutamate.

What I find a bit strange, is when flec. worked for me for the year prior to using it now, I never had one breakthrough. That was before finding this site, therefore, I was eating my normal diet, dining out in restaurants, eating minimally processed foods, and having occasional drinks. Questions I'm asking myself are: Has more damage been done over time? Why does flec. work if it's a sodium channel blocker, by way of dopamine (It's not a glutamate blocker)? Why does dysopyramide work for you and not me? Why did betas make it sooooo much worse for me, unless I have adrenal insufficiencies? Why are my sulfur levels so low, when I should be getting plenty of sulfur via the type of foods I'm eating? Why were my glutamate levels somewhat low, but my glutamine levels high? Not questions to be answered, I'm just pondering.

Back to reading the bioscience link again.
Richard

Here's a bit on galantamine, from the ibedenone.org site.

ACETYLCHOLINE HELPS MAINTAIN HOMEOSTASIS
Before getting to some of the evidence supporting the authors' conclusion, let's look at its implications. Homeostasis is one of the key concepts of biology. It is the process by which an organism, or an organ, or a single cell, maintains equilibrium by adjusting its physiological processes to compensate for the effects of disruptive outside forces, such as changes in temperature or chemical composition, or assault by hostile microorganisms. Since homeostasis is necessary for the proper functioning, and ultimately the survival, of our cells, it's fair to say that anything, such as acetylcholine, that plays an important role in that process is very important indeed. This suggests the obvious: that any nutritional precursor to such a vital compound - in this case, choline - should be high on our priority list.

An intriguing clue regarding the importance of acetylcholine is its ubiquity in nature. Although we think of it primarily as a neurotransmitter, ACh is found, more than any other such type of molecule, in a wide variety of creatures - including those that do not even have a nervous system. It has been detected in bacteria and in primitive organisms, such as blue-green algae, yeasts, fungi, protozoa, worms, and sponges. It has also been discovered in some primitive plants.
[www.galantamine.cc]

Would excess free glutamate be considered a disruptive outside force? I don't know much about acetylcholine, and even if it's in the same cells as glutamate and GABA, so I'll be reading more about it. More ponderings.
I still have so much to learn, and can't seem to retain it all, esp. if it was discussed months back.

Richard

In the conf. room I posted this remark:

The only other thing that stood out between our two hair analysis (I'm not sure how to make this word plural), was lithium (Li). David's fell slightly, but that put him on the edge of the green/yellow line, so he's teetering on low, whereas mine was below normal. I might need to do some searching on Li.

Here's a very interesting study I found, pertaining to the above, in part:

MADISON, WI. -- July 6, 1998 -- Researchers at the University of Wisconsin Medical School have solved the puzzle of how one drug - lithium - can effectively stabilise both the wild euphoria and the crushing melancholy that are the hallmark of manic depression, or bipolar disorder.
As reported in the July 7 Proceedings of the National Academy of Sciences, the researchers found that in mice brains, lithium exerts a push/pull effect on the neurotransmitter glutamate, eventually causing it to level off in a stable zone where it can control both extremes.

It goes on to say: The research findings support clinical observations, he noted. “It takes a few weeks before lithium begins to relieve depression and mania in bipolar patients,” he said. “It’s now apparent an adaptive reuptake mechanism that brings glutamate within a ‘normal’ range works over time to curb both the highs and lows.”

[www.pslgroup.com]

Another study:

The muscarinic-gated atrial potassium channel IKACh is the prototypical member of the KG channel family. IKACh is formed by stoichiometric assembly of GIRK1 and GIRK4 subunits, and is a component of the parasympathetic signaling pathway that culminates in heart rate slowing (Corey et al., 1998; Krapivinsky et al., 1995a; Wickman and Clapham, 1995). Acetylcholine released following vagal stimulation binds muscarinic receptors on the surface of sino-atrial and atrio-ventricular nodal cells and atrial myocytes, triggering a G protein signaling cascade that stimulates IKACh and modulates the activity of several other ion channels and enzymes. Previously, we generated mice lacking a functional GIRK4 gene (Wickman et al., 1998). While the mice were viable and appeared normal, cardiac myocytes obtained from the mice lacked the IKACh conductance. Furthermore, the mice exhibited a blunted heart rate response to vagal stimulation and adenosine administration, and were resistant to pacing-induced arrhythmias (Kovoor et al., 2000; Wickman et al., 1998).
[clapham.tch.harvard.edu]

This may have been posted before, but for anyone interested, these are various studies done on neurotransmitters:
[www.neurotransmitter.net]

Richard

Richard,

From your post above:

"The muscarinic-gated atrial potassium channel IKACh is the prototypical member of the KG channel family. IKACh is formed by stoichiometric assembly of GIRK1 and GIRK4 subunits, and is a component of the parasympathetic signaling pathway that culminates in heart rate slowing (Corey et al., 1998; Krapivinsky et al., 1995a; Wickman and Clapham, 1995). Acetylcholine released following vagal stimulation binds muscarinic receptors on the surface of sino-atrial and atrio-ventricular nodal cells and atrial myocytes, triggering a G protein signaling cascade that stimulates IKACh and modulates the activity of several other ion channels and enzymes. Previously, we generated mice lacking a functional GIRK4 gene (Wickman et al., 1998). While the mice were viable and appeared normal, cardiac myocytes obtained from the mice lacked the IKACh conductance. Furthermore, the mice exhibited a blunted heart rate response to vagal stimulation and adenosine administration, and were resistant to pacing-induced arrhythmias (Kovoor et al., 2000; Wickman et al., 1998).
[clapham.tch.harvard.edu]

Would this imply that a IHACh channel blocker might do the trick for VMAFrs?
I seem to remember a new AF drug being researched that was highly selective in blocking certain channels - I wonder if IHACh was one of them.............. I'm intrigued that the IHACh-lacking mice were resistant to pacing-induced arrythmias.

Mike F.