23 replies to this topic

[addx]

I've been playing with Memantine for years now and it's hard describing what it does for me. Recently, I've taken up a sport - cycling, it doesn't hurt my back.

But still, I have a hard time doing sports. As I start exercise, if it is anything hard (like going uphill) I start getting lightheaded, completely losing my breath that it almost pains me, tunnel vision, weakness in mind and body and I simply have to give in to the overwhelming feeling. This makes exercise very poor, exhausting and I feel like I'm not really accomplishing anything. Forcing myself regularly doesn't seem to help this situation, it doesn't get better. People tell me it's because I need to get in shape, but I just can't seem to do that - get in shape. The only half-way out of this is to exercise for a long time, at least an hour. After about 45 minutes to an hour I seem to "get used" to exercise more and this seems to help will throbing tunnel vision and lack of breath. But, at 45 minutes, my body is already drained enough and while I can produce burst of energy without becoming disabled aftewards, it is a "tired energy". At that point my performance is comparable to that of other people after 45 minutes, but up until that point I lose my breath too easily.

Other than that, I can hardly feel physical exercise to be satisfying in any means and I often have a bad time after it, I feel exhausted, drained, mentally fatigued, I don't feel I've done good to myself.

I'm 33 years old now.

Now, Memantine steps in. One pill. Even without exercise I've noticed Memantine drastically decreases tunnel vision or increases peripheral vision. But the magical thing for me is - it does this during exercise. Taking 1 pill of memantine before exercise made my performance on a bike uphill similar or even better than that of my friend. Compared to performance without memantine - I'd say I could push at least 50 or 100 times (im not kidding) more harder before I'd overexert myself. It's not the same kind of overexertion, with memantine, I'd stop when the pain in the muscles gets too strong. Without memantine, I'd simply feel overwhelmed throught the body and mind, a complete lack of breath and energy and my head would feel like it wants to explode from blood pressure and tunnel vision throbing. Without memantine, I'd get overwhelmed after like 20-30 meters of steep uphill, with memantine I could power on for 10-15 minutes.

Without memeantine my muscles feel depressed and drained. With memantine my muscles feel ready. During exercise with memantine I can feel the vigour in my muscles, I can get satisfaction from pushing them, reaching my goal. I keep peripheral vision (important for downhill) during the whole time, my head is relatively clear, I can react to incoming objects and so on.

The difference is night and day. Memantine does produce a certain muscle power increasing effect - hypertonia is listed as a sideeffect and I believe this is what allows me to use my muscles in spite of some inherent CNS-weakness. I've seen people say that its cholinergic effect is known to "crush" muscles (it does worsen my anal hemoroid clench if I take it regularly). Memantine is also neuroprotective for low oxygen states and against glutamate storms (which may be induced by lack of oxygen?) and this might be what's keeping the "tunnel vision" at bay.

Anyway, memantine allows me to sustain and most importanly REALLY enjoy physical exercise. My muscles don't feel sore the next day, maybe a little weak, which is normal, day two I'm fully ready, so there's no damage being done to anything, I've done this too many times already.

At this point I'm taking memantine only before exercise as I've noticed it worsens my hemorhoids.

It might be noted that I've had sever asthma in childhood which I've somehow "outgrown" during puberty. I've not had asthma attacks since in spite of smoking or being exposed to the same allergens from childhood (in whatever amounts). As child I've had regular bouts of blood coughing asthma attacks that would persist for weeks. They would be induced by allergens (feathers, dust) or simply exercise(worst in cold air).

I do not believe one "outgrows" such a condition but that the body finds some way to compensate. Whatever it is, it has symptoms of its own.

I'm kinda guessing that a part of the compensation mechanism is an "aversion to exercise response" and my idea is that Memantine seems to override it.

Interestingly enough, Memantine has shown significant success in treatment of fibromyalgia, I think 2 studies now show this. Also, I have a genetic predisposition towards dementia and alzheimers which is often considered a form of diabetes. Tunnel vision on the other hand could be a symptom of low blood sugar (at least in the brain).

I'm not sure what to make of this. I'm happy I found a way to feel vigour in my muscles and to enjoy motion and sports and not feel horrible afterwards (but infact want more).

I've claimed many times - being into sports is as much a symptom of health as it is a cause of health. When I take my memantine, I want to do sports I feel vigour in my muscles, I feel satisfaction from "physical succeeding/work". Without memantine, I could force myself for months and still would not get anywhere, I still couldn't produce 1 minute of good "true power" performance that I can produce now simply by taking memantine.

So, any thoughts? Anyone have similar issues?

Edited by addx, 05 May 2015 - 08:53 AM.

[addx]

I've found studies confirming what I feel, referenced/quoted below
 

Interestingly enough, Memantine has shown significant success in treatment of fibromyalgia, I think 2 studies now show this. Also, I have a genetic predisposition towards dementia and alzheimers which is often considered a form of diabetes. Tunnel vision on the other hand could be a symptom of low blood sugar (at least in the brain).
...
Memantine is also neuroprotective for low oxygen states and against glutamate storms (which may be induced by lack of oxygen?) and this might be what's keeping the "tunnel vision" at bay.

http://www.ncbi.nlm....pubmed/21106713

Memantine prevents hypoglycemia-induced decrements of the cerebral energy status in healthy subjects.

Abstract
CONTEXT:
The risk to develop dementia is significantly increased in diabetes mellitus. Memantine, an N-methyl-D-aspartate receptor antagonist, which is clinically applied in dementia, has been shown to exert neuroprotective effects under hypoglycemic conditions in rats.
OBJECTIVE:
We hypothesized that memantine may prevent hypoglycemia-induced decrements in the cerebral high-energy phosphate, i.e. ATP, metabolism to exert its neuroprotective action under these conditions.
DESIGN AND PARTICIPANTS:
In a randomized, double-blind crossover design, we applied memantine vs. placebo in 16 healthy male subjects and examined the cerebral high-energy phosphate metabolism by (31)phosphor magnetic resonance spectroscopy, hormonal counterregulation, and neurocognitive performance during hypoglycemic glucose clamp conditions.
RESULTS:
We found increments in hormonal counterregulation and reduced neurocognitive performance during hypoglycemia (P < 0.05). Cerebral ATP levels increased upon hypoglycemia in the memantine condition as compared with placebo (P = 0.006) and remained higher after renormalizing blood glucose concentrations (P = 0.018), which was confirmed by ATP to inorganic phosphate ratio (P = 0.046). Phosphocreatine levels and phosphocreatine to inorganic phosphate ratio remained stable throughout the experiments and did not differ between conditions (P > 0.1 for both).
CONCLUSION:
Our data demonstrate that memantine preserves the cerebral energy status during experimentally induced hypoglycemia in healthy subjects. An improved neuronal energy status may thus be involved in the neuroprotective effect under these conditions and may qualify memantine as potential future option to combat cognitive impairments and dementia in diabetes.

My reaction to memantine implies that I'm not that healthy, at least in terms of brain ATP turnover. My cerebral glucose status is not induced by a clamp as in the study, but given my reaction I would presume that I have hypoglycemic prone brain, it seems like a chronic condition for me. I presume exercise (very much like the clamp) exacerbates my brain hypoglycemic condition and memantine counters/rescues this for me as it does in the study for the clamped subjects.

For me, memantine enables full view peripheral vision with full detail, allows easy switching focus between objects, tracking multiple objects and so on. But it seems to do so only for me, not as a general effect. I've given memantine to my wife and 2 friends. Neither of them reported any effects to their field of vision, peripheral vision, ability to track objects or see dramatically more detail/sharpness across the entire field of view. I have also not seen this effect mentioned much in peoples experience of the drug..

For me, this is the biggest effect of this pill, noticeable immediately after taking the pill, it takes maybe 5 minutes to start...and yet others can't notice this effect at all. For me it was there immediately and super noticeable since the first pill I ever took.. I've stopped and started taking it many times and as said now taking it intermittently...

So I trust my specific and very positive reaction to Memantine is something worth exploring...

Edited by addx, 05 May 2015 - 11:48 AM.

[crazepharmacist]

While I can't say memantine directly increased physical endurance it did eradicate my social anxiety allowing me to become engrossed in my workout in the gym rather than worrying what others around me are thinking.That alone, indirectly has improved my physical fitness levels by a great amount. 

Edited by crazepharmacist, 05 May 2015 - 01:17 PM.

[addx]

There is a hint of effectiveness against social anxiety or at least one manifestation of it. I suffer from gaze intolerance, especially during sex and memantine eradicates it, especially during sex. This was also a noticeable effect since the first pill.. but I tend to get used to the effects and stop noticing them after a while, not sure they're still there... also, I tend to start to feel somehow uncomfortable after a while of taking 2 pills a day. Some kind of strange anxiety and a lack of noticeable effects that it had in the beginning always cause me to drop out after a while and immediately return after a day or two. All literature points to the fact that 20mg is the only effective dosage, not less, not more, either way you get more sideeffects and no good effects, but for me, I get extremely good effects from a single pill, or even half a pill. If anything people get a headache or feel dumber from that first pill...

[addx]

Oh yea, I noticed the only sideeffect that annoys me - it makes me kinda dyslexic. I work with numbers and I noticed when I'm on memantine (not sure about dosage) I tend to mix up the order of digits of a number I've seen and am trying to type. It feels like I read the number correct and typed it correct, even while looking at the original and replaying my own (wrong) memory of it in my head I can't see the difference.

Also I'm prone to reading words wrongly (wrong but similar), also typing in wrong order, usually whole words or mangling them somehow... It goes away when I stop taking memantine.

Edited by addx, 05 May 2015 - 03:02 PM.

[addx]

More studies

http://jpet.aspetjou.../322/2/721.full

Memantine Inhibits ATP-Dependent K+ Conductances in Dopamine Neurons of the Rat Substantia Nigra Pars Compacta

Exposure of the dopamine neurons to a hypoglycemic medium inhibits SNc dopamine neurons through activation of KATP channels (Marinelli et al., 2000). Therefore, we tested whether the spontaneous firing rate of dopamine neurons recorded with the multielectrode system could be increased by memantine in hypoglycemic conditions. To avoid an excessive metabolic stress, we perfused the slices in 1 mM glucose, a threshold dose for dopamine neuron hyperpolarization (Marinelli et al., 2000). As shown in Fig. 6, when the recordings were obtained in ACSF containing 1 mM glucose, a low overall firing rate was detected (compare with Fig. 3). In these experimental conditions, 100 μM memantine reversibly increased the firing rate of presumed dopamine neurons. When glucose was increased to 2 mM in the same slice, the overall firing rate increased, and 100 μM memantine became ineffective, in accordance with what was previously observed in normoglycemic conditions (Fig. 3).

We have shown that, in addition to its expected property of NMDA receptor antagonist, memantine reduces neuronal hyperpolarization mediated by the opening of KATP channels in dopamine neurons of the SNc in a dose-dependent manner.

According to our observations, memantine does not affect the basal firing activity of the dopamine neurons in physiological conditions, whereas in conditions of metabolic stress, a significant effect of memantine emerges, resulting in recovery of firing activity of previously silenced dopamine neurons.

This property may be particularly relevant in terms of firing dependent dopamine release and in relation to prevention of neuronal loss in Parkinson's disease.

Our results show that memantine does inhibit NMDA responses in the SNc; however, memantine may also have beneficial results in Parkinson's disease patients because it reduces dopamine neuron silencing through closure of KATP conductances.

I've "felt" most of what they say in these studies. The effect is not "endless" it merely "rescues" a situation. It does not make you exercise better, it makes you exercise less bad. You can't increase dosage to get more gains, it can only rescue an existing metabolic loss at a certain dosage, anything over that and you get only sideeffects. This makes it a very good and "proper" drug. But still leaves the question, why do I need it?

[addx]

Oh yea, I noticed the only sideeffect that annoys me - it makes me kinda dyslexic. I work with numbers and I noticed when I'm on memantine (not sure about dosage) I tend to mix up the order of digits of a number I've seen and am trying to type. It feels like I read the number correct and typed it correct, even while looking at the original and replaying my own (wrong) memory of it in my head I can't see the difference.

Perhaps found a way to explain better. Memantine causes me to see trees, not the forest. I see(sense/know) each tree of the forest in detail simultaneously somehow. (I don't have to mention views are great, I love looking at open spaces).

This also translates to object tracking, I see all cars on the road move and I "feel/sense/calculate their motion" simultaneously, this enables easy switching of focus between all these objects, it enables you to follow around one object while simultaneously noticing the motion of other objects in relation to whichever you're focusing.

However, when looking at a string of digits - I, similarly to the above, see all digits simultaneously. There is no order, they're all there. I look at the number, see all digits simultaneously and a validating thought occurs that I have noticed and remembered the number since all digits were "seen"/identified/recognized. But the order was not properly "seen"/assesed/recognized and is not remembered properly. Worst thing is that I could swear I read/recognized the digits and remembered them and are replaying the memory of them correctly, but infact I mess up the order when storing it into memory.

Edited by addx, 05 May 2015 - 05:03 PM.

[Dichotohmy]

What you're describing is textbook exercise intolerance. It's really interesting that memantine is helping you exercise to your actual physical conditioning - sadly, I never noticed any such benefit when I tried memantine for 2 months.

Do you have any condition, like maybe dysautonomia, to explain a CNS malfunction in musculoskeletal control and/or any other signs of mitochondrial dysfunction?

Also, have you ever looked into baking soda, catalase, or creatine supps? These things had a subtle, but kind of unpredictable benefit for my exercise throughput (uphill trail running and weights), but don't really help with the abnormally protracted recovery time (3-7 days) and the physical malaise I suffer after every 30-45 minute session.

[addx]

What you're describing is textbook exercise intolerance. It's really interesting that memantine is helping you exercise to your actual physical conditioning - sadly, I never noticed any such benefit when I tried memantine for 2 months.

Do you have any condition, like maybe dysautonomia, to explain a CNS malfunction in musculoskeletal control and/or any other signs of mitochondrial dysfunction?

Also, have you ever looked into baking soda, catalase, or creatine supps? These things had a subtle, but kind of unpredictable benefit for my exercise throughput (uphill trail running and weights), but don't really help with the abnormally protracted recovery time (3-7 days) and the physical malaise I suffer after every 30-45 minute session.

 

Thanks for reading..

 

Ive used baking soda in a few occasions succefully to rescue myself out of some weird metabolic states I would find myself in (unable to control body temperature, shivering, muscles clenching and aching and bowel cramps-diarhea). It would provide immediate relief, thank god. Ive not attempted to use it regularly as therapy though. Have not tried the other two. Ive used creatine maybe 10 years ago or so when I was going regularly to the gym at one period, I cant say I would expect much from it, but I can try it..

 

Yes, it reads like textbook exercise intolerance, but I cant get rid of it through "exposure". It also seems I shouldnt be able to starve my brain of energy to the point of almost knocking myself unconscious simply by exercising no matter how hard.

Also, a week of skiing (snowboarding) would normally restore my exercise ability years ago but not in the last 5-6 years. After my last skiing week last year it took me a month to recover from all the aches it caused, I could barely sit straight (I have back issues that also seem related)... there was no improvement.. but I felt worse, a lot worse.

 

There was a series of events 5-6 years ago that caused some change in me. I do think I have some predispotions to these kind of issues but the situation I put myself through 5-6 ago was completely abnormal. It started with some sever emotional events after which I ate perhaps 500 calories a day for a month or longer, lost 20kgs, consumed various drugs daily (cocaine and weed) for months and have not been the same since. Im not really overweight, 99kgs was lifetime max, 79kgs was my adult lifetime min achieved right at the end of that fast, Im usually somewhere in between like 85kgs, which is relatively ok for 188cm.

 

The first symptom I noticed, after I started to eat relatively normally again was metabolic chaos after eating a meal. Id have severe hypoglycemic bursts after meals, I would sweat profusely only from armpits (armpits sweat glands are differently connected than all other), get confused, irritated and all that. Also issues with body temperature, unable to get warm, aching muscles especially calf for days and various other metabolic symptoms. Id also often feel as if adrenaline was draining from my adrenals, you know the gut feeling as if you dropped 5 feet without warning. I noticed that meals caused most of the difficult (hypoglycaemic) issues and after some research opted for a zero-carb diet. The zero-carb diet sure did solve the issues immediately but also launched me into a hypomania (my first and only, but definitely a hypomania, Ive read extensive literature neurologic, pharmacologic and psychologic) that persisted for around a month. The hypomania was great for me, I did good on the job, ensured the next 5 years of work, I got so much mental relief from it, I felt great, no issues whatsoever....Anyway as time went on I was feeling better than ever (hypomanic) I slowly introduced carbs back into the diet. At that point, immediately after a meal with some carbs I dropped out of the hypomania. I collapsed on the sofa and spent the next 2 days basicly not moving from it, lucky it was a weekend. My body temperature was 2 degrees below normal the entire weekend no matter what I did and I felt really weak. It started getting back to normal for weeks after that. Again I did research, low temperature a general malaise pointed to thyroid, went and had it checked, my levels were just on the edge, low. Went to a doctor and had him check it out an he had some thyroid hormones perscribed. I noticed very little or no effect from hormones. I went and bought T3T4 mix of thyroid hormones for more immediate effects, upped my dosage relatively gradually 4, 5 times from perscribed, I noticed no effects (no sideeffects either). I took it for maybe 2 months ending with the maximum dose Ive seen persribed for people that have had their thyroid removed. I gave up on that then.

Anyway, most of the symptoms started subsiding or changing into other symptoms. Ive had cognitive issues for periods, maybe even emotional can be related to it. The ones that remain a constant are IBS crampy painful diarrheas, the ones in the middle of the night are my favorite. Also sometimes very acidic stool that burns like hell and seems and most probably is basicaly pure bile. I cant really say Im sensitive to any foods, I have not noticed anything like that during my life. Ive rathre been known to eat any combo and get away with it. But Ive also been known not be able to drink a glass of water for a day or two without it immediatlely turning into water-stool and exiting. I cant really relate these periods of IBS to what I eat, I can relate them to other things though... Interestingly these bouts of painful diarrhea did not start 5-6 years ago, they just became a lot more chronic then. But I remember as a kid, if I drank cold juice immediately after waking up (which is something I loved to do) I would get a painful diarhea in the next 5 minutes 50% of the times. It seemed to be a reaction to cold beverage or cold sweet beverage, not sure, I never drank water, heh but I feel water could do it as well. Anyway I would be done with them in 5 minutes, but I would almost die in the process, losing vision, blurring, everything becoming yelowish, the pain was exruciating, but after it came out all was completely normal as if nothing happened I went normally to school, ate whatever I want and have a normal stool from it. I stopped doing that (drinking cold juice) when I figured it out, only had it happen to me a few times by accident and most often at night (i think if my back gets uncovered in the cold it causes it), but since 5-6 years ago the diarheas accompany me very often for periods of time and constant bloatyness and discomfort, slight pain etc.. also nonsmelly gas, kinda points to a small intenstine bacterial overgrowth... but 5 years of it? I took various antibiotics over the years.. I feel its just another dead end..

 

Anyway, thats that, the first clear benefit I ever got from anything I tried was memantine. 

 

I noticed from day one, immediately, I can lift myself up 2-3 times on it and I like doing it, I "feel the power". I couldnt lift myself even once without it. And that has nothing to do with exercise intolerance or anything exercise causes in my brain, but purely available muscle power. Memantine not only enables me to keep my brain operating normally during straining exercise but it litterally allows me to use all the power in my muscles that normally seems denied (centrally I imagine) - regardless if I just started pulling-lifting-running or am I running out of breath. 

My muscles without memantine feel weak similarly to how they feel when you sometimes get up in the morning and cant twist open a bottle from the fridge. The muscle weakness is not really noticeable in normal activites, walking around, moving around. There is no clumsyness or anything like that, Im very precise in almost all circumstances. Also, as said, before a few years my muscles would often ache as if Id been overexercising while in fact I would barely move around all day. I relate these aches to the feeling of muscle weakness, they seem to be the same emotion on a scale - inflammation.

 

Throughout all this time I took blood tests on at least 15 occasions, especially during my selfimposed thyroid hormone dose escalation. Other than the mentioned low T3T4 (which went away) theres nothing off in my bloodwork. I checked all hormones, various markers and the usual.. glucose levels, cholesterol, liver function and hemo. My fasting and long term glucose was always perfect... cholesterol good, testosterone high, ... oh yea, I admit liver function would sometimes be raised as if i was losing muscle (ALT and one other i think), doc said to think nothing of it though... nothing on ultrasound.. on any organs. Cortisol would often be high, but not over the limit... not sure that could be a cause, and after 5 years I should be cushinglike and Im not.

 

This is a seriously long post.... 

Edited by addx, 05 May 2015 - 09:11 PM.

[OneScrewLoose]

Memantine simply reduces the strength of incoming stimuli as an uncompetitive (this is vastly different from non-competitive) antagonist at the NMDA receptor. It can very well block the feeling of exhaustion in your muscles. What dose do you take (not how many pills)?

I take 35mg/day for neuropathy, as it blocks a lot of the stimuli that trigger it.

[OneScrewLoose]

Oh yea, I noticed the only sideeffect that annoys me - it makes me kinda dyslexic. I work with numbers and I noticed when I'm on memantine (not sure about dosage) I tend to mix up the order of digits of a number I've seen and am trying to type. It feels like I read the number correct and typed it correct, even while looking at the original and replaying my own (wrong) memory of it in my head I can't see the difference.

Also I'm prone to reading words wrongly (wrong but similar), also typing in wrong order, usually whole words or mangling them somehow... It goes away when I stop taking memantine.

 

My guess is that you're not taking it on a regular basis. Memantine significantly blocks certain acetylcholine receptors, which can have exactly these effects.. Over a month, they will upregulate, sometimes beyond their initial amount, giving you an even stronger signal than what you started with. However, if you take it every now and then, this reaction is absolutely, positively, unsurprising.

Edited by OneScrewLoose, 05 May 2015 - 10:44 PM.

[Area-1255]

 

Oh yea, I noticed the only sideeffect that annoys me - it makes me kinda dyslexic. I work with numbers and I noticed when I'm on memantine (not sure about dosage) I tend to mix up the order of digits of a number I've seen and am trying to type. It feels like I read the number correct and typed it correct, even while looking at the original and replaying my own (wrong) memory of it in my head I can't see the difference.

Also I'm prone to reading words wrongly (wrong but similar), also typing in wrong order, usually whole words or mangling them somehow... It goes away when I stop taking memantine.

 

My guess is that you're not taking it on a regular basis. Memantine significantly blocks certain acetylcholine receptors, which can have exactly these effects.. Over a month, they will upregulate, sometimes beyond their initial amount, giving you an even stronger signal than what you started with. However, if you take it every now and then, this reaction is absolutely, positively, unsurprising.

 

You should be more specific, mematine antagonizes nictotinic AcH receptors., most potently the alpha-7-nicotinic receptor, it however boosts overall acetylcholine activity and potentiates hippocampal AcH activity. Secondary to NMDA activity.

 

J Alzheimers Dis. 2007 Dec;12(4):319-33.

Memantine acts as a cholinergic stimulant in the mouse hippocampus.

Drever BD1, Anderson WG, Johnson H, O'Callaghan M, Seo S, Choi DY, Riedel G, Platt B.

Author information

 

Abstract

The non-competitive NMDA receptor antagonist memantine, currently prescribed for the treatment of Alzheimer's disease, is assumed to prevent the excitotoxicity implicated in neurodegenerative processes. Here, we investigated the actions of memantine on hippocampal function and signalling. In behavioural experiments using the water maze, we observed that memantine (at 2 mg/kg) reversed scopolamine-induced learning deficits in mice. When acutely applied to mouse hippocampal slices, memantine caused a significant upward shift in the population spike input-output relationship at 10 and 100 microM, and a corresponding downward shift in latency, indicative of overall enhanced synaptic transmission. This action was blocked by the muscarinic antagonist scopolamine (10 microM) but not by the NMDA antagonist MK-801 (10 microM) or the GABA antagonist bicuculline (20 microM). Further, memantine occluded potentiation induced by 50 nM carbachol (CCh), while enhancing inhibitory actions of CCh at 1 microM, suggesting additive actions. As anticipated for an NMDA antagonist, 100 microM (but not 10 microM) memantine also inhibited tetanus-induced long-term potentiation (LTP), and NMDA-induced Ca;{2+} signals were blocked in cultured hippocampal neurones at 10 microM (by 88%). Overall, our data suggest actions of memantine beyond NMDA receptor antagonism, including stimulating effects on cholinergic signalling via muscarinic receptors. These interactions with the cholinergic system are likely to contribute to memantine's therapeutic potential.

PMID:   18198419   [PubMed - indexed for MEDLINE]

 

 

J Pharmacol Exp Ther. 2005 Mar;312(3):1195-205. Epub 2004 Nov 2.

Memantine blocks alpha7* nicotinic acetylcholine receptors more potently than n-methyl-D-aspartate receptors in rat hippocampal neurons.

Aracava Y1, Pereira EF, Maelicke A, Albuquerque EX.

Author information

 

Abstract

The N-methyl-d-aspartate (NMDA) receptor antagonist memantine is an approved drug for treatment of Alzheimer's disease (AD). Other such treatments are cholinesterase inhibitors and nicotinic acetylcholine receptor (nAChR)-sensitizing agents such as galantamine. The present study was designed to test whether memantine exerts any effect on the cholinergic system, in particular the Ca(2+)-conducting alpha7(*) nAChR, in cultured hippocampal neurons. Memantine caused a concentration-dependent reduction of the amplitudes of whole-cell currents evoked by the alpha7(*) nAChR-selective agonist choline (10 mM) or by N-methyl-d-aspartate (NMDA) (50 muM) plus glycine (10 muM). It also inhibited tonically activated NMDA receptors. Memantine was more potent in inhibiting alpha7(*) nAChRs than NMDA receptors; at -60 mV, the IC(50) values for memantine were 0.34 and 5.1 muM, respectively. Consistent with an open-channel blocking mechanism, memantine-induced NMDA receptor inhibition was voltage and use-dependent; the Hill coefficient (n(H)) was approximately 1. Memantine-induced alpha7(*) nAChR inhibition had an n(H) < 1 and showed a variable voltage dependence; the effect was voltage-independent at 0.1 muM, becoming voltage-dependent at >/=1 muM. Thus, memantine interacts with more than one class of sites on the alpha7(*) nAChRs. One is voltage-sensitive and therefore likely to be within the receptor channel. The other is voltage-insensitive and therefore likely to be in the extracellular domain of the receptor. It is suggested that blockade of alpha7(*) nAChRs by memantine could decrease its effectiveness for treatment of AD, particularly at early stages when the degrees of nAChR dysfunction and of cognitive decline correlate well.

 

 

 

Edited by Area-1255, 06 May 2015 - 02:46 AM.

[OneScrewLoose]

Agreed! What happens though, in this case is very peculiar and fascinating. It blocks the alpha 7 nicotinic receptors in such a way that the receptors upregulate past their original point. This is what contributes to the increased ACh activity! It's why Memantine can have such hard side-effects at first that turn around and become a cognitive boost after a month. It remains to be seen whether the NMDA antagonism is part of the cause of the alpha 7 upregulation.

 

http://www.ncbi.nlm....pubmed/15372325

http://www.nature.co...id=NEURO-201201

 

 

Inactivity-induced upregulation of Dα7-nAChR

An increase in mEPSC amplitude suggests that there has been an enhancement in the function or number of postsynaptic nAChRs. Notably, mEPSCs recorded from curare-treated motor neurons also had a faster rate of decay than mEPSCs of untreated motor neurons (Fig. 1g). When mEPSC decays were fit with a double exponential function, we found a similar fast component (τ(fast)) in both mock- and curare-treated motor neurons (control, 0.32 ± 0.03 ms; treated, 0.27 ± 0.03 ms). However, the contribution of this τ(fast) was significantly increased with synaptic blockade (P < 0.05; Fig. 1g). This result suggested that the increased mEPSC amplitudes were due to upregulation of a particular subtype of nAChR. Notably, vertebrate α7-nAChRs have been shown to have faster deactivation kinetics than other subtypes^18, 19. Although there is a paucity of specific inhibitors for these vertebrate receptors, memantine has previously been used to block them²⁰. Indeed, we found that the increase in mEPSC amplitude following curare treatment was blocked when memantine was used during recording (control, 8.3 ± 0.9 pA; treated, 8.7 ± 0.9 pA) (Fig. 1h), suggesting that the increase is memantine sensitive and therefore probably carried by Dα7 receptors. To examine whether the increase in mEPSC amplitude was due to an increase in Dα7 receptor number, we used an antibody to Dα7 (anti-Dα7) to immunostain cultures that were either mock or curare treated for 24 h. Indeed, we observed a clear and reproducible increase in Dα7 signal in most neurons, including GFP-labeled motor neurons, from curare-treated cultures compared with the signal from mock-treated cultures (Fig. 1i).

 

We next examined whether the increase in Dα7 induced by synaptic blockade could be observed in adult brains in vivo and, further, whether this homeostatic response was specific to the Dα7 subunit. To do this, whole brains were mock or curare treated in culture; cell viability was confirmed by showing that protein synthesis could indeed be induced in cultured brains (Supplementary Fig. 1j). We incubated wild-type brains in culture medium either with or without curare for 15 min, 12 h or 24 h, and protein levels were analyzed by immunoblot analysis. Notably, we found that Dα7 protein levels were increased by more than 60% after 24 h of curare treatment (Fig. 1j), but no differences were observed with shorter incubations. In addition, similarly to the enhancement in mEPSCs, the increase in Dα7 protein persisted for at least 5 h (Supplementary Fig. 1b). By contrast, other nAChR subunits, including Dα1, Dα2, Dβ1 and Dβ2, showed no significant change following synaptic inactivity (Fig. 1j). Altogether, our results showed a selective increase in Dα7 receptors that probably underlay the increased amplitudes of mEPSCs following prolonged synaptic block.

If you want the full benefits of Memantine, you have to take it consistently, long enough, so that the a7 receptors can upregulate significantly. This seems to take up to a month at a consistent, daily dosage.

Edited by OneScrewLoose, 06 May 2015 - 03:29 AM.

[addx]

Thanks for all your posts and sorry for not making it clear, one pill in all my texts means 10mg.

As said, I've been taking memantine for years and unlike now, I took it regularly before. I took a steady dose of 20mg for months, but also played around with higher doses and lower doses. The issue is, all the benefits I like from memantine crap out after I reach a steady dosage. I can get them each time I restart, but I can't keep them. Which is why I currently resort to taking it intermittently for exercise.

From most studies memantine dosage of 20 mg is the only correct dosage. Most compelling studies towards this dosage are PPI studies which show memantine to rescue PPI at 20mg but distort it at either lower or higher dosage.

Let me recapitulate the issues I would like to discuss.


1) Muscle ability

Memantine increases muscle strength for me or rather removes muscle weakness. This has nothing to do with being in shape, but is rather obvious at any time if I try to lift or hold something. I trust this effect of memantine is listed as the side-effect of "hypertonia". My question is, what specific interaction of memantine with the body chemistry produces this effect?

It is my idea that I feel an increased ability to move muscles voluntarily.

I have mentioned that I feel ability in my muscles, readyness, vigour, willingless to move and satisfaction from achieving precise movement, making sports activities fun. This a subjective sense of muscles - how ready and disposed they are towards your subjective/voluntary will.

I can't help but to pair this effect with memantine D2 agonism. D2 receptors regulate (excite) voluntary movement. http://www.ncbi.nlm....pubmed/19145338.

If this is caused by D2 agonism then it is quite understandable that I "get used to it" as something upregulates to counter this as it always does when dopamine receptors are pushed.

Sensing your own body is a function of NMDA receptors as well, blocking them removes the ability to sense your body as your own and under your control (I've been down a ketamine trip), so that may play a part in it, but if this effect is dependant on memantines NMDA antagonism - it shouldnt crap out after a while.

2. Stimuli gating

The visual (and auditory) effects of increased simultaneous object recognition, increased sharpness, increased detail - at the expense of dyslexic-like effects (simultaneous seeing all digits of a number but ignoring the order). Also, this was the most profound effect I noticed first - I am able to enjoy visuals during sex and simultaneously it makes me feel digusted by my own fetishes, but it makes sex more spontaneous. Both of these effects are most apparent for me when starting memantine, the first pill I take has the most profound effects.
So, question is what specific effect of memantine causes these effects? Since it wears out I'm prone to beleive it's also D2 related...but then again NMDA receptor govern attention to stimuli... but I can't see how antagonism would increase detail, except by spreading attention (processing time) more evenly across stimuli.

3. Brain energy levels

Memantine seems to annihilate brain-level exercise intolerance. As said, even a short burst of energy sends my brain into throbbing tunnel vision and the notion that my head will explode from lack of air. Memantine rescues this completely for me and I'm able to persist at hard muscle loads for periods comparable to other normal people. I'm interested in what specific effect of memantine would cause this. I offered a study towards an explanation showing that memantine rescues ATP levels in hypoglycaemic conditions which may be what happens to me when I enter this throbbing tunnel vision.

These three effects, muscle ability, stimuli gating and brain energy levels make physical activity very inviting and rewarding. The ability to move and the ability to track objects and react properly and to persist at it. Also to note, listening to loud dance music is very activating in the sense of making me dance when on memantine. This may be a result of a combo 1. + 2., increased audio sharpness and tracking paired with increased muscle readyness (disinhibition of movement).


All in all, it seems I'm mostly responding to D2 agonism effects? Which also explains why it craps out over time.

Memantines partial NMDA antagonism is most probably not something the body compensates, whatever effects it has, they should persist indefinitely.
Cholinergic antagonism may play a role and is something the body would compensate for. Having said that, I've not felt any substantial cognitive boost after a month or more of taking a steady dose, so I suspect I'm not reacting to cholinergic action that much. Brain energy levels might be a consequence of the ATP effects of mememantine mentioned in the study a few posts above. The only thing I'm not sure of, is if I lose the "brain energy levels" perk after a while... I have not tracked that...



Also to note, I don't think memantine NMDA antagonism can "hide" the pain of muscles being overexerted. I have not noticed any painkilling effects to note (other than the ability to endure exercise). Also a single pill of 10mg of memantine is hardly enough to produce substantial NMDA antagonism to provide pain relief IMO. Also, if I really did override any pain signals I should have at least felt the pain the next day or day after..
If without memantine I couldnt go uphill for more than 30 seconds and with memantine I was able to do it for 10-15 minutes (not without pain, in fact there was great pain but I was able to endure), I should have ripped my muscles to pieces, but they felt ok the other day, slightly soar. I've often overexerted myself to the point of having metabolic issues the other day, shivering and so on. This is not the case with memantine, it feels healthy, it doesnt feel like I hurt my muscles. I remember back when I was younger I could exert the same control over my muscles as I can with memantine today. I could push them until they swell up and become inflamed. I know how it looks and feels.

Edited by addx, 06 May 2015 - 08:25 AM.

[addx]

Memantine simply reduces the strength of incoming stimuli as an uncompetitive (this is vastly different from non-competitive) antagonist at the NMDA receptor. It can very well block the feeling of exhaustion in your muscles. What dose do you take (not how many pills)?

I take 35mg/day for neuropathy, as it blocks a lot of the stimuli that trigger it.

It doesn't really block pain for me, I feel the pain but I also feel enough control to make them move in spite of the pain, but most of all it allows me to keep my brain running during exercise.

I currently take 10mg just before an exercise usually every 2 days, but depends on weather, work ans such. That means my daily intake is 5mg on average.

[OneScrewLoose]

It's not it that blocks pain, it's that it's blocking so of signals in the first place by blocking glutamate signalling. Therefore, no pain to begin with.

I'm not sure how strong this mechanism is at only 10mg though.

[addx]

Ill try and explain what happens on memantine with my body.

Normally, I have issues across my entire back, I feel thoracic area bones are constantly misaligned, one shoulder different(lower or more protruding) than the other, one leg longer, hip rotation, ribs and vertebrae misaligned. I also constantly "crack" and "click" my entire back including neck more extensively than any chiropractor and have been doing it for 5 years. I have issues where shoveling snow for 30 minutes causes like new extra 5 degrees of rotation in my lower back/hips, causing my legs to be very much unequal length and inability to stand straight(ish).
Last time it happened my left leg was longer literally 5cms, I walked like quasimodo, left leg outward like 30cm(because its longer), back curved at almost 90 degrees, limping. I came home and rotated-cracked it back almost to normal and restored my ability to stand straight (i wonder how official medicine views this, as chiropractice is not medicine, but i cant see any alternative medical procedure for this, so, what would a doctor do for me if I didnt fix myself?). All my joints are like that, loose, and all my back muscles seem either athrophied or rigid/hypertonic/unable to release. I can't perform the same movements with both hands, or even legs. They all seem to be displaced and compensating for each others displacement in some way, rigid, clenched, painful. From anus to head, clenched muscles, from hemorhoids to thoracic and cervical muscles...

So now you get how I feel. In no condition to exercise.

When I'm on memantine - I still feel all of that, all of those aches and I also constantly align and chiro my joints (I have to, I often lose the ability to rotate my neck to the right and have to chiro it back to an acceptable position). But when I start to exercise I have power in my muscles, an increasing sense of power.

Last time I went on the bike uphill with memantine, after a 5 minutes of pedaling my body incresingly felt like a well oiled machine. My Alordosis (lower back curve pathologically straightening) simply "let go" and my lower back suddenly curved in regular lordosis fashion. The new position of the lower back caused my hips to change posture(outwardly somehow) and this made my legs feel equal length. This causes the inequality in my legs to revert to normal and I pedaled each side the same (which I normally can't). The pedaling motion finally became free and fluid, equal on both sides and using only the appropriate muscles with no compensation. This allowed even more power to flow as the motion was correct now.
At that point I felt like exercise is really doing me good (while still feeling regular exertion/lactic acid pain in muscles that does make me stop from time to time), releasing clenched back and hip muscles, putting me in proper position.. I can't really say that this happened because of inherent memantines pain killing ability but rather because it provided true power/control to ALL muscles which eventually triggered opioidergic action (exerted muscles call for mu-opiod agonism, mu-opioid marks them for growth/repair) which may have killed some pain but is also beneficial for muscles and it means they'll grow and repair - this is what you're after with exercise. I can't achieve this feeling without memantine (and I should, I was able to when I was younger).

I have a feeling if I resume my memantine-exercise therapy that I'll actually fix my joint/back/muscle issues. It feels as my posture is becoming better. I've just recently RTGed my entire back so I have the "before" shots, I wonder how things will go. This is the only thing so far that gives hope regarding my joint/back/muscle aches. My state has been deteriorating for 5 years or more. Currently RTG shows lumbal alordosis, slight spine rotation, L4-L5 degeneration just started. I used to have a lot of lower back pain and it seems my body responded with lumbal alordosis - since this started I never had any lumbal pain, but also since then my thoracic spine hurts every day of the year, every position, I just can't get comfortable.

Anyway, I thank the gods of pharmacology for memantine as it offered hope for my back and also made me love sports (at least biking). I can't wait for my next bike session and this is something I havent been able to say in quite a long time.

I'll report back here from time to time. Not sure much else can be said of this, I thank everyone for discussing.

I do urge people who feel like I do to give memantine a try.

[addx]

It's not it that blocks pain, it's that it's blocking so of signals in the first place by blocking glutamate signalling. Therefore, no pain to begin with.

Having said that up above, I'd like to offer my view of pain.

NMDA circuits govern CNS attention to stimuli (and so also pain).

For me, pain is a signal originating from the offending peripheral neurons. A pain signal has intensity.

This signal is preprocessed accordingly awarded attention - via NMDA modulation.

Pain that receives attention is consciously felt. The amount of conscious "feeling" depends on the original intensity and the awarded attention.

Pain that isn't awarded attention is not consciously felt.

Also, the body(nervous system) generally tries to react to change and so a constant signal (of pain) should increasingly become ignored by the nervous system. It doesn't change so it doesnt warrant attention, this way attention can be awarded to other happening stimuli(changes).
So, attention is increasingly reduced if the signal is constant. If you barely touch a wound or a sore spot it hurts a lot more than if you dont, that's because attention has been reduced, but your touch causes a slight change in pressue->pain signal, but this slight change causes NMDA to again divert attention to the entire pain signal from that area - which was until then mostly ignored. This is why a slight touch causes high pain.

Dynamic short term NMDA adaptation in attention to stimuli is eventually translated into a long term adaptation.

Development of this "attention ignoring" requires the NMDA circuits and is in fact the process of development of TOLERANCE (even to drugs). This is why NMDA antagonists reduce development of tolerance. NMDA antagonist do not remove tolerance, but they reduce the development of it. IMO the circuits which aprimarily modulate tolerance (to everything) are kappa opioidergic. I have some topics here about that and this is why we have people waiting in line for the next kappa opioid antagonist experimental drug.

Edited by addx, 07 May 2015 - 01:38 PM.

[addx]

I bought some agomelatine, going to start taking it. I took it 3 years ago also in combination with memantine and at that time I remember having the most back-pain free day in my life, I actually went for a run... going to see if I can repeat this... if nothing at least itll help my mood and insomnia 

 

Interistingly

 

http://www.ncbi.nlm....pubmed/24636462

 

Agomelatine but not melatonin improves fatigue perception: a longitudinal proof-of-concept study.

 

 

Edited by addx, 07 May 2015 - 06:44 PM.

[OneScrewLoose]

Let me reiterate what I am trying to say. I am taking 35mg of memantine to greatly compress NMDA signals. Note that Memantine is uncompetitive (this isn't non-competitive), and only begins to work when the receptor fires. This mean that I am compressing the NMDA signals, without removing them, like DXM would.

The effect of this is as such. Glutamate is the primary excitatory neurotransmitter. So when we receive signals, the glutaminergic system is activated. These signals are then passed to the thalamus for sensory gating, so that they don't overwhelm the individual (this is a simplistic, overarching view. There is definitely more going on, but it serves the purpose for this discussion. At my dose, what seems to be going on is that it removes the glutaminergic signals. The signals don't even make it to the thalamus to be processed. It's like they never existed in the first place. I can't guarantee that this is happening, as this is partially anecdotal. But memantine at that dose changed my neuropathy and my life more than anything else ever did. I must note that I took doses from 10-20mg before, and it didn't do this. Before I took it, I predicted that I would need a dose between 30-40mg for this to happen, as doses up to 20mg are used simply to compress the signal enough to prevent excitotoxicity in Alzheimer's patients. I knew that I would need to beyond that to remove pain signals. My hypothesis was right, at least in me, I slowly built up to 40mg and it did exactly that, changing my life drasticcally. It's the most important substance I take, 50mg was too much. I now take 35 as the reduced stimulation at 40mg lowers my ability to feel sexual pleasure and caused near complete anorgasmia.

I do need to reiterate that this isn't conclusive science, so take it with a grain of salt.

@addx, if you are having constant joint pains, please look into Cissus Quadrangularis. I recommend the Primaforce brand due to it's standardization. It runs about $25 a 120 count bottle. You usually need to only take one per day. It's pretty cheap and I've seen it have profound effects on people's joint pain. 

[Ark]

What you're describing is textbook exercise intolerance. It's really interesting that memantine is helping you exercise to your actual physical conditioning - sadly, I never noticed any such benefit when I tried memantine for 2 months.

Do you have any condition, like maybe dysautonomia, to explain a CNS malfunction in musculoskeletal control and/or any other signs of mitochondrial dysfunction?

Also, have you ever looked into baking soda, catalase, or creatine supps? These things had a subtle, but kind of unpredictable benefit for my exercise throughput (uphill trail running and weights), but don't really help with the abnormally protracted recovery time (3-7 days) and the physical malaise I suffer after every 30-45 minute session.

Thanks for reading..

Ive used baking soda in a few occasions succefully to rescue myself out of some weird metabolic states I would find myself in (unable to control body temperature, shivering, muscles clenching and aching and bowel cramps-diarhea). It would provide immediate relief, thank god. Ive not attempted to use it regularly as therapy though. Have not tried the other two. Ive used creatine maybe 10 years ago or so when I was going regularly to the gym at one period, I cant say I would expect much from it, but I can try it..

Yes, it reads like textbook exercise intolerance, but I cant get rid of it through "exposure". It also seems I shouldnt be able to starve my brain of energy to the point of almost knocking myself unconscious simply by exercising no matter how hard.
Also, a week of skiing (snowboarding) would normally restore my exercise ability years ago but not in the last 5-6 years. After my last skiing week last year it took me a month to recover from all the aches it caused, I could barely sit straight (I have back issues that also seem related)... there was no improvement.. but I felt worse, a lot worse.

There was a series of events 5-6 years ago that caused some change in me. I do think I have some predispotions to these kind of issues but the situation I put myself through 5-6 ago was completely abnormal. It started with some sever emotional events after which I ate perhaps 500 calories a day for a month or longer, lost 20kgs, consumed various drugs daily (cocaine and weed) for months and have not been the same since. Im not really overweight, 99kgs was lifetime max, 79kgs was my adult lifetime min achieved right at the end of that fast, Im usually somewhere in between like 85kgs, which is relatively ok for 188cm.

The first symptom I noticed, after I started to eat relatively normally again was metabolic chaos after eating a meal. Id have severe hypoglycemic bursts after meals, I would sweat profusely only from armpits (armpits sweat glands are differently connected than all other), get confused, irritated and all that. Also issues with body temperature, unable to get warm, aching muscles especially calf for days and various other metabolic symptoms. Id also often feel as if adrenaline was draining from my adrenals, you know the gut feeling as if you dropped 5 feet without warning. I noticed that meals caused most of the difficult (hypoglycaemic) issues and after some research opted for a zero-carb diet. The zero-carb diet sure did solve the issues immediately but also launched me into a hypomania (my first and only, but definitely a hypomania, Ive read extensive literature neurologic, pharmacologic and psychologic) that persisted for around a month. The hypomania was great for me, I did good on the job, ensured the next 5 years of work, I got so much mental relief from it, I felt great, no issues whatsoever....Anyway as time went on I was feeling better than ever (hypomanic) I slowly introduced carbs back into the diet. At that point, immediately after a meal with some carbs I dropped out of the hypomania. I collapsed on the sofa and spent the next 2 days basicly not moving from it, lucky it was a weekend. My body temperature was 2 degrees below normal the entire weekend no matter what I did and I felt really weak. It started getting back to normal for weeks after that. Again I did research, low temperature a general malaise pointed to thyroid, went and had it checked, my levels were just on the edge, low. Went to a doctor and had him check it out an he had some thyroid hormones perscribed. I noticed very little or no effect from hormones. I went and bought T3T4 mix of thyroid hormones for more immediate effects, upped my dosage relatively gradually 4, 5 times from perscribed, I noticed no effects (no sideeffects either). I took it for maybe 2 months ending with the maximum dose Ive seen persribed for people that have had their thyroid removed. I gave up on that then.
Anyway, most of the symptoms started subsiding or changing into other symptoms. Ive had cognitive issues for periods, maybe even emotional can be related to it. The ones that remain a constant are IBS crampy painful diarrheas, the ones in the middle of the night are my favorite. Also sometimes very acidic stool that burns like hell and seems and most probably is basicaly pure bile. I cant really say Im sensitive to any foods, I have not noticed anything like that during my life. Ive rathre been known to eat any combo and get away with it. But Ive also been known not be able to drink a glass of water for a day or two without it immediatlely turning into water-stool and exiting. I cant really relate these periods of IBS to what I eat, I can relate them to other things though... Interestingly these bouts of painful diarrhea did not start 5-6 years ago, they just became a lot more chronic then. But I remember as a kid, if I drank cold juice immediately after waking up (which is something I loved to do) I would get a painful diarhea in the next 5 minutes 50% of the times. It seemed to be a reaction to cold beverage or cold sweet beverage, not sure, I never drank water, heh but I feel water could do it as well. Anyway I would be done with them in 5 minutes, but I would almost die in the process, losing vision, blurring, everything becoming yelowish, the pain was exruciating, but after it came out all was completely normal as if nothing happened I went normally to school, ate whatever I want and have a normal stool from it. I stopped doing that (drinking cold juice) when I figured it out, only had it happen to me a few times by accident and most often at night (i think if my back gets uncovered in the cold it causes it), but since 5-6 years ago the diarheas accompany me very often for periods of time and constant bloatyness and discomfort, slight pain etc.. also nonsmelly gas, kinda points to a small intenstine bacterial overgrowth... but 5 years of it? I took various antibiotics over the years.. I feel its just another dead end..

Anyway, thats that, the first clear benefit I ever got from anything I tried was memantine.

I noticed from day one, immediately, I can lift myself up 2-3 times on it and I like doing it, I "feel the power". I couldnt lift myself even once without it. And that has nothing to do with exercise intolerance or anything exercise causes in my brain, but purely available muscle power. Memantine not only enables me to keep my brain operating normally during straining exercise but it litterally allows me to use all the power in my muscles that normally seems denied (centrally I imagine) - regardless if I just started pulling-lifting-running or am I running out of breath.
My muscles without memantine feel weak similarly to how they feel when you sometimes get up in the morning and cant twist open a bottle from the fridge. The muscle weakness is not really noticeable in normal activites, walking around, moving around. There is no clumsyness or anything like that, Im very precise in almost all circumstances. Also, as said, before a few years my muscles would often ache as if Id been overexercising while in fact I would barely move around all day. I relate these aches to the feeling of muscle weakness, they seem to be the same emotion on a scale - inflammation.

Throughout all this time I took blood tests on at least 15 occasions, especially during my selfimposed thyroid hormone dose escalation. Other than the mentioned low T3T4 (which went away) theres nothing off in my bloodwork. I checked all hormones, various markers and the usual.. glucose levels, cholesterol, liver function and hemo. My fasting and long term glucose was always perfect... cholesterol good, testosterone high, ... oh yea, I admit liver function would sometimes be raised as if i was losing muscle (ALT and one other i think), doc said to think nothing of it though... nothing on ultrasound.. on any organs. Cortisol would often be high, but not over the limit... not sure that could be a cause, and after 5 years I should be cushinglike and Im not.

This is a seriously long post....

If your looking for options to add try NSI-189,stablon, semax and pilicome, Stacked preworkout. I think memantine will benefit from the additions above, but caution you to try anything new without further research.

I hope this information puts you on happy trails.

Edited by Ark, 08 May 2015 - 07:48 PM.

[sthira]

@addx

The alignment issues you're describing: misaligned thoracic bones, the lordosis, your shoulder unevenness, differences in leg length, hip rotation problems, misaligned torso, imbalanced ribcage, the cracking of your joints, overly-loose joints, clenched muscles... These are all issues very commonly dealt with in Iyengar yoga. Get thee to a Iyengar-based studio near you, and sign up for some classes. The practice will change your life. I'm a ballet dancer, always in various states of misignment, and this type of yoga is truly transformative. And, you'll learn to control some of the stress caused by your suffering through targeted breathing techniques. By all means continue taking memantine if it's working for you. But do consider some alignment-based yoga. People like you and me are who this specific system of yoga was designed to help with alignment issues.

[Snozzberry Scientist]

I used to mess around with dissociatives daily (NMDA antagonizers/agonizers) for years they gave me super human strength and endurance plus took away all muscle pain way beyond amphetamines (was prescribed) haven't thought about taking anything of that class now that I live a healthier lifestyle... (except magnesium Taurate) but will have to consider using memantine... How has memantine + exercise effected cognition OP?

[Snozzberry Scientist]

Also wanted to note.... in very high doses all NMDA Drugs block pain and invoke anasthesia beyond opiates (400mg of oxy included) or any other drug I have consumed... Low doses you can feel pain but it is not alarming or a big deal you are just aware of it... It is hard to explain.... Even 10 mg of memantine or 30 mg DXM/ equivalent doses of any other NMDA drug change your view of pain temporarily....