Neuroprotection memantine

Strike me lucky

Well-Known Member
http://www.ncbi.nlm.nih.gov/pubmed/19536110

Abstract
Memantine shows clinically relevant efficacy in patients with Alzheimer's disease and Parkinson's disease. Most in vivo and in vitro studies attribute the neuroprotective effects of memantine to the blockade of N-methyl-D-aspartate (NMDA) receptor on neurons. However, it cannot be excluded that mechanisms other than NMDA receptor blockade may contribute to the neuroprotective effects of this compound. To address this question, primary midbrain neuron-glia cultures and reconstituted cultures were used, and lipopolysaccharide (LPS), an endotoxin from bacteria, was used to produce inflammation-mediated dopaminergic (DA) neuronal death. Here, we show that memantine exerted both potent neurotrophic and neuroprotective effects on DA neurons in rat neuron-glia cultures. The neurotrophic effect of memantine was glia dependent, as memantine failed to show any positive effect on DA neurons in neuron-enriched cultures. More specifically, it seems to be that astroglia, not microglia, are the source of the memantine-elicited neurotrophic effects through the increased production of glial cell line-derived neurotrophic factor (GDNF). Mechanistic studies showed that GDNF upregulation was associated with histone hyperacetylation by inhibiting the cellular histone deacetylase activity. In addition, memantine also displays neuroprotective effects against LPS-induced DA neuronal damage through its inhibition of microglia activation showed by both OX-42 immunostaining and reduction of pro-inflammatory factor production, such as extracellular superoxide anion, intracellular reactive oxygen species, nitric oxide, prostaglandin E(2), and tumor necrosis factor-alpha. These results suggest that the neuroprotective effects of memantine shown in our cell culture studies are mediated in part through alternative novel mechanisms by reducing microglia-associated inflammation and by stimulating neurotrophic factor release from astroglia.
 

Remy

Administrator
When you have too much glutamate (excitatory neurotransmitter that is nasty in excessive amounts), it will bind to NMDA receptors and allow calcium to flow freely into the cell. This high intracellular calcium may be responsible for a number of the symptoms associated with MECFS. High intracellular calcium can cause conformational (shape) changes to the mitochondria so they don't work well anymore.

There are a number of strategies one can use to reduce intracellular calcium...magnesium is one that many of us use. It is an NMDA antagonist like memantine. I think some people see benefit from magnesium more from its NMDA antagonist properties rather than a true deficiency of magnesium (though surely there are exceptions).

Calcium channel beta blockers like verapamil may also help to decrease intracellular calcium.

I have a prescription for memantine...looking forward to giving it a shot! It looks to be well tolerated in most people with diarrhea and sleepiness being the most common adverse effects.
 

Who Me?

Well-Known Member
@Remy I have tried it. Even half a dose, I think 2.5 mgs just completely drugged me out. I did take it in the morning so maybe for me it would be better at night?

:bear: would this work for guinea pig? or this?:clown: haha? or this? :cow: Guinea moose?
 

Paw

Well-Known Member
I think some people see benefit from magnesium more from its NMDA antagonist properties rather than a true deficiency of magnesium (though surely there are exceptions).
Interesting. I was certain I would do well with memantine (given my past reactions and symptoms), but it consistently gives me flu-like symptoms. Magnesium, however, I tolerate very well.
 

Strike me lucky

Well-Known Member
I wastaking between 5 to 10mg in the morning. It did initially give me some mental clarity and energy but eventually wheres off so tolerance must be occurring. I have read it can increase cortisol but ot doesnt feel like hc, maybe more specific in its other functions.

Main reason i was using it was to help lower benzo tolerance through its nmda antagonist properties which it helps some with. I think its mental clarity may come through blocking effects of tnf alpha???

Recently started using it at night to see if this would help better with tolerance and it seems too. So its energy effects to seem to worry sleep. Maybe mixing up fatigue with inflammation that memantine treats??
 

loki

Well-Known Member
Hi i recently got my hands on memantine and feel like forming increasing complex sentences isn't such a pain in the ;) anymore... Ran out of b and D vits and of curcumin yesterday though... Memantine puts me to sleep like an angel which im very thankful for! And i could cut down the Prednisone complete :D
See what future shows up... Dex. Memantine. B2 B12 D Curmin.
 

loki

Well-Known Member
well i'm about 2 weeks on memantine now and i don't wanna look back! thanks to this drug, it actually gave me huge parts of my mind back! It's completely different to the time before i took memantine! i have my memory back, i can sleep like a baby, i've got my movement improved by 50%, all these little things please me and damn most beautiful thing is that my memory's back... jeeeeez
 

weyland

Well-Known Member
well i'm about 2 weeks on memantine now and i don't wanna look back! thanks to this drug, it actually gave me huge parts of my mind back! It's completely different to the time before i took memantine! i have my memory back, i can sleep like a baby, i've got my movement improved by 50%, all these little things please me and damn most beautiful thing is that my memory's back... jeeeeez
What kind of dosing?
 

loki

Well-Known Member
20-25mg Memantine p.o. + 20-30mg Prednisolone p.o. both in the morning

it's important to combine it with a corticosteroid to buffer the cytokines, because memantine decreases glutamate levels but doesn't affect neuro or systemic body inflammation. so, to decrease IL 1-beta, IFN-gamma and other usual suspects corticosteroids are helpful. sadly, they have their downsides and it's not recommended long term you know... but i feel it being the best combination at the moment. cleaned the house today, can write like before i got ill again, can calculate better, sort better, eyesight's clear and sharp, mind is sharp again, skin's getting normal, everything's much easier. decreasing glutamate excitotoxicity is a good thing and provides great improvements:)
 

Who Me?

Well-Known Member
@weyland and I had the opposite effect. I had total brain fog, worse than I ever had, felt horrible. Never again. But if you want to get some PM me and I'll tell you where. It's pretty cheap. Or check out resources under supplements and medications.
 

weyland

Well-Known Member
20-25mg Memantine p.o. + 20-30mg Prednisolone p.o. both in the morning
Wow. That's pretty high dosing to start out with.

and I had the opposite effect. I had total brain fog, worse than I ever had, felt horrible. Never again.
This is more in line with what I have heard for this drug (though for ADHD, not ME mind you.) Most people have to start out with 2mg for a while and titrate up slowly to 10 or 20mg.
 

Who Me?

Well-Known Member
Wow. That's pretty high dosing to start out with.


This is more in line with what I have heard for this drug (though for ADHD, not ME mind you.) Most people have to start out with 2mg for a while and titrate up slowly to 10 or 20mg.
I took 2 mgs once in the a.m. I was fogged and drugged the entire day. I think 2 days later I tried it again, same thing. I can't afford to be out of it like that so I stopped it.
 

loki

Well-Known Member
hm the first time i took 5mg and was pretty baked, i know that feeling but it subsides with time. i don't have any side effects other than that my memory seems to be better and i'm better in doin 2 things at a time, for me it does make things better. i can even cook! never cooked before anymore:hilarious:
 

loki

Well-Known Member
i guess it's something like a puzzle, with many many pieces and while doin it, you always have to step away from it, look at it and see if it is right, it's always ascending and descending, as you have to arrange and calibrate all the time until the system seems to work. When the energy's flowing back it's a sign you're puzzling right, if you feel like your brain's getting flooded something's wrong. I experimented with Prednisone and NMDA blockers and they change things to the best from all other drugs i ever tested out. but anyway, i only seem to scratch the surface.
 

loki

Well-Known Member
so, there's definately potential, i'm not dead yet and will not throw the towel until. i'll wait for PLX3397 and will try to remove the glia with it. when i did my homework correctly i'll be good as new, either nothing happens or i deteriorate, whatever happens i'll be prepared ...
 

loki

Well-Known Member
[bimg=no-lightbox]http://i.imgur.com/fT9wk4W.jpg[/bimg]

like this, don't know what the parallels of Down Syndrome and CFS/ME are but i guess there are parallels...
 

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