Namenda response

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FatherOf2
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Re: Namenda response

Postby FatherOf2 » Thu Apr 17, 2014 4:35 pm

Thanks, Irinka.

There is Strattera used for ADHD, which has a similar antagonistic action on NMDA receptors as Namenda. Some adults who used Namenda also reported good improvements on Strattera. But they also said that the effect from Strattera was temporary. Has anybody here used Strattera on kids?

Then there is Lamictal, which inhibits sodium channels. The effect from Lamictal ranges from great social improvements and focus to zombie-like. I guess it all depends on the dose. I want to try Lamictal next. Right now we reduced Namenda dose to see what it does.

Irinka
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Re: Namenda response

Postby Irinka » Thu Apr 17, 2014 9:49 pm

Thank you for your suggestion. I am going to look into it.
My son is 9 years old and was diagnosed with Autism at 3.
Since then we tried a lot of things including chelation, MB12 shots, various supplements, homeopathy etc. He did improve but there was always some regression with almost any trial.

FatherOf2
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Re: Namenda response

Postby FatherOf2 » Fri Apr 18, 2014 12:18 am

Strattera may cause irritability because its main action is norepinephrine reuptake inhibitor. So, cross it out. This document is agood summary of medications for a similar condition to ASD:
http://www.fragilex.org/wp-content/uploads/2012/08/Medications_for_Individuals_with_Fragile_X_Syndrome2012-Oct.pdf

A couple of things caught my attention: "Anticonvulsants used to target mood instability such as carbamazepine, lamotrigine and valproic acid can occasionally be effective for aggressive behavior/SIB, and thus should be considered as second‐line therapy."

And this one: "L‐acetylcarnitine (LAC), a nutritional supplement, was shown to have an apparent beneficial effect on hyperactive‐impulsive behavior in boys with FXS and ADHD without side effects in a placebo‐controlled trial. Specifically, a reduction of hyperactivity and improvement in social behavior were observed in patients with FXS treated with LAC, as determined by the Conners' Global Index Parents and the Vineland Adaptive Behavior Scale. Results from a single study suggest that LAC (20‐50 mg/kg/day) may represent a safe alternative to the use of stimulant drugs for the treatment of ADHD in some cases for boys with FXS (Torrioli 2008)."

For some reason I always thought that Acetyl L-Carnitine causes higher hyperactivity, not lower. We tried it, but never saw anything positive. It may be worth trying it again.

FatherOf2
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Re: Namenda response

Postby FatherOf2 » Sat May 03, 2014 11:08 am

A quick update. After improvements at 10mg/day seemed to disappear, we increased Namenda dose to 15mg/day. We saw a apike in improvements in the first 4 days and then a regression. At the same time we saw increased irritability and defiance. DS was saying "no" to almost anything we said. That continued for almost 2 weeks. Then we reduced the dose to 10mg, irritability and deiance reduced. Then we reduced the dose again to 5mg/day, and irritability and defiance were gone. One week ago we stopped Namenda completely, thinking that it wasn't doing anything, and saw reduced attention, eye contact, and response to his name. We are thinking of re-starting Namenda at the low dose of 5mg/day. It seems to be optimum for us. There are studies showing that autistic brains have more synapses than a normal brain, indicating over-active neurons (prevalance of excitatory action over inhibitory one). So, blocking excitatory receptors (specifically NMDA receptors) with Namenda seems to be the right direction for us. There are some new drugs for Fragile X under trials, which work similarly to Namenda (reducing the activity of glutamate receptors) and resulting specifically in better social behaviors. Here is an interesting presentation about one of such drugs, which explains many other things about autistic brains:

http://www.autismtreatmenttrust.org/wp-content/uploads/2013/06/Treating-Autism-Autism-Treatment-Trust-June-2013-Conference-NNZ-2566-in-Rett-Syndrome-and-Autism-Spectrum-Disorders-%E2%80%93-Role-and-Update-v2.pdf

FatherOf2
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Re: Namenda response

Postby FatherOf2 » Sun May 04, 2014 11:23 pm

This article http://www.alzheimerioliga.lt/axura/preclinical_data/role_of_glutamate/index.htm explains how NMDA receptors work and the role of glutamate. This article http://www.alzheimerioliga.lt/axura/preclinical_data/signal-to-noise_hypothesis/index.htm explains how Namenda works at a neuron level and how its action is different from Mg.

To simply put it, in a normal brain, Mg blocks NMDA receptors in the resting state, preventing Ca ions from entering the neuron and changing its state. When a neuron is supposed to fire, enough glutamate is released from a presynaptic neuron to release Mg and open NMDA channels for calcium ions to enter the postsynaptic neuron. In Alzheimer’s patients, the background glutamate levels are elevated such that Mg is displaced and no longer blocks NMDA receptors even under resting conditions, leaving the calcium channels open and allowing influx of calcium ions into the neuron during its resting state. This creates electrical noise, which masks the desired signal created by a presynaptic release of extra glutamate during an impulse transmission. Namenda is "a stronger Mg". It blocks NMDA receptors more efficiently during the neuron's resting state and unblocks it during an impulse transmission. I have a question: what happens to Mg during Namenda treatment. Does it continue its role as an NMDA blocker, working together with Namenda, or does it get replaced with Namenda? In the latter case, the body may get used to work without Mg such that you will need to supplement it heavily after Namenda termination (which is what I am finding now).

Another interesting question is why autistic neurons have over-sensitive/over-active NMDA receptors. It turns out that this happens during neuroinflammation (inflammatory mediators increase glutamate release http://www.cnsspectrums.com/aspx/articledetail.aspx?articleid=1590). So, drugs that reduce neuroinflammation are supposed to have the same effect as drugs blocking NMDA receptors. The next question is why is there neuroinflammation in the first place?

FatherOf2
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Re: Namenda response

Postby FatherOf2 » Mon May 05, 2014 4:48 pm

Here is another drug similar to their Namenda: Acamprosate or Campral (n-acetyl-homo-taurine), a sythetic analogue of Taurine. Besides blocking NMDARs, Acamprosate also blocks mGluR5, whose increased activity is the main reason for autistic behaviors in FragX patients, and activates GABA receptors.

http://www.ncbi.nlm.nih.gov/pubmed/20213249
"Glutamatergic dysfunction is implicated in the pathophysiology of fragile X syndrome (FXS). We report on the first trial of acamprosate, a drug with putative mGluR5 antagonism, in three adults with FXS and autism. Medical records describing open-label treatment with acamprosate in 3 patients with FXS and a comorbid diagnosis of autistic disorder were reviewed. In all three patients, acamprosate was associated with improved linguistic communication. Three patients received acamprosate over a mean 21.3 weeks of treatment. All patients showed global clinical benefit as rated with the Clinical Global Impressions-Improvement scale. Marked communication improvement was unexpected and has potential implications for the treatment of FXS, as well as idiopathic autism."

This is interesting "Protein blotting demonstrated an up-regulation of NMDA-receptor subunits after acamprosate as well as after memantine or MK-801, in comparison to controls" (http://www.ncbi.nlm.nih.gov/pubmed/11369029). While blocking NMDA receptors, long-term consumption of these compounds (including alcohol) leads to the overproduction (upregulation) of NMDA receptors and tolerance to these compounds, which is what we observed on Namenda. It is well known that a sudden alcohol abstinence causes "the excessive numbers of NMDA receptos to be more active than normal and to contribute to the symptoms of delirium tremens and excitotoxic neuronal death. Withdrawal from alcohol induces a surge in release of excitatory neurotransmitters like glutamate, which activates NMDA receptors" (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2268999/).

alexsdad
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Re: Namenda response

Postby alexsdad » Tue May 06, 2014 4:14 pm

FatherOf2 - Have you tested the glutamate level on your son? We did the neurotransmitters test (urine) from Pharmasan Labs ordered by our DAN but our neuro didn't want to give any credit to the test. He didn't want to do spinal tab either though. I wasn't sure if the Pharmasan Lab test result was accurate to be honest. Some say GABA level is not even measurable. Most of the neurotransmitters were high including GABA, Taurine, Glycine, Glutamate, Dopamine, DOPAC, and Norepinephrine in our test. You seem to have done a lot of research on this so let me ask you this - Should I worry about balancing with other neurotransmitters when glutamate inhibitors are used?

FatherOf2
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Re: Namenda response

Postby FatherOf2 » Tue May 06, 2014 5:44 pm

alexsdad wrote:Should I worry about balancing with other neurotransmitters when glutamate inhibitors are used?

I wouldn't worry about it. Inflammatory response of the immune system in our kids increases glutamate levels and excitotoxicity. So, lowering glutamate actually works towards more balanced neurotransmitters. Namenda doesn't reduce glutamate. It blocks NMDA receptors just like a bottle cork. But, my theory is that without reducing glutamate, blocking NMDA receptors by Namenda will only lead to the production of more NMDA receptors, which brings you back to too much excitotoxicity. That is why I think the addition of Lamictal to reduce glutamate might be a good idea.

alexsdad
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Re: Namenda response

Postby alexsdad » Tue May 06, 2014 6:11 pm

I was particularly worried about GABA-Glutamate balance. I've given GABA to my son and he did horribly on that so at least I know GABA is not something he needs more. If both are high like my son (assuming the urine test done for my son was accurate and reliable) wouldn't inhibiting NMDA receptors result in too much of GABA available for his brain? Namenda and Lamictal at the same time sounds scary.

FatherOf2
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Re: Namenda response

Postby FatherOf2 » Wed May 07, 2014 10:06 am

alexsdad wrote:Wouldn't inhibiting NMDA receptors result in too much of GABA available for his brain?

It is quite possible. How did your son react to GABA (fell asleep or became too hyperactive) and at what doses and in what form? For eaxmple, my son doesn't react to straight GABA, but L-theonine causes huge mood swings. Piracetam, which is a derivative of GABA, improved memory and reaction time without visible changes in behaviors. There are so many nootropics based on GABA, which instead of calming down increase hyperactivity. All kids are different.

alexsdad
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Re: Namenda response

Postby alexsdad » Wed May 07, 2014 11:58 am

He became very mellow, wept out of nothing on GABA. We tried twice and the results were the same. I'm thinking maybe high GABA and glutamate were balancing each other then Namenda broke the balance in his brain. The later effect of Namenda wasn't exactly the same as GABA but it was similar Lamictal - Initial good response followed by slowing him down. After all this, I am not sure if my son really suffers from too much glutamate regardless of what the urine test says.

FatherOf2
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Re: Namenda response

Postby FatherOf2 » Wed May 07, 2014 3:48 pm

alexsdad wrote:He became very mellow, wept out of nothing on GABA. We tried twice and the results were the same. I'm thinking maybe high GABA and glutamate were balancing each other then Namenda broke the balance in his brain. The later effect of Namenda wasn't exactly the same as GABA but it was similar Lamictal - Initial good response followed by slowing him down. After all this, I am not sure if my son really suffers from too much glutamate regardless of what the urine test says.

How much Namenda and Lamictal did you use? We are going back on Namenda this weekend, but on a tiny dose of either 2.5mg/day or 5mg/day. We saw reduction in eye contact and response to his name after we stopped Namenda. I was hoping that he would improve off Namenda if given enough time, but at almost 2 weeks, he is still the same. As far as Lamictal is concerned, we'll start it later in the summer. But I am not sure if I will go all the way to a normal dose of 7.5mg/kg. I will try to gauge an improvement after each dose increase, and if there is no improvement, I plan to back off to the last dose that gave improvements. Since ds doesn't have seizures, I feel comfortable giving the smallest dose possible. I'll use Kastania's 2.5mg increments.

alexsdad
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Re: Namenda response

Postby alexsdad » Wed May 07, 2014 7:23 pm

FatherOf2 wrote:
alexsdad wrote:He became very mellow, wept out of nothing on GABA. We tried twice and the results were the same. I'm thinking maybe high GABA and glutamate were balancing each other then Namenda broke the balance in his brain. The later effect of Namenda wasn't exactly the same as GABA but it was similar Lamictal - Initial good response followed by slowing him down. After all this, I am not sure if my son really suffers from too much glutamate regardless of what the urine test says.

How much Namenda and Lamictal did you use? We are going back on Namenda this weekend, but on a tiny dose of either 2.5mg/day or 5mg/day. We saw reduction in eye contact and response to his name after we stopped Namenda. I was hoping that he would improve off Namenda if given enough time, but at almost 2 weeks, he is still the same. As far as Lamictal is concerned, we'll start it later in the summer. But I am not sure if I will go all the way to a normal dose of 7.5mg/kg. I will try to gauge an improvement after each dose increase, and if there is no improvement, I plan to back off to the last dose that gave improvements. Since ds doesn't have seizures, I feel comfortable giving the smallest dose possible. I'll use Kastania's 2.5mg increments.


We tried various doses. DAN was going by Chez's protocol and was willing to use up to 15mg but my son wasn't able to tolerate anything beyond 5mg per day. Later I thought he was doing well around 1.5mg - 2mg per day but after we quit there was no difference so maybe it didn't do anything at that low dose. It really bothers me that often times I can't even tell if an intervention is helping or not.

Regarding Lamictal, I can't find the dosing sheet now but the target dose was 40mg and my boy was somewhere above 20kg at that time. We did it with his neurologist and it took 2 months to get to the target dose. When we weaned him off, it took another three weeks I think. You have to go up and down slowly with Lamictal. My son didn't do well on Lamitcal and I suspected it messed up with his glutamate level.

Some kids change on AED like day and night and I think it's it is because the seizure is directly interfering with their developments. So when the seizure is controlled and EEG is normalized they can clearly think and talk all of sudden. Other times, AED can normalize EEGs and control seizure (if there is any) but kids still don't make progress. It's because there is underlying problem that causes the seizure and developmental delay and AED only addresses the seizure. I think the latter is my son's case. He outgrew seizure and not on any AED now but he didn't outgrow the developmental problem.

alexsdad
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Re: Namenda response

Postby alexsdad » Thu May 08, 2014 1:46 pm

FatherOf2 or anyone who might know - If I want to explore the opposite direction of Namenda what would be a good candidate? (other than giving MSG :) ) Would Piracetam be a good one? I started to wonder if the urine neurotransmitters test is something I can trust.

alexsdad
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Re: Namenda response

Postby alexsdad » Thu Jun 12, 2014 10:31 am

FatherOf2 - Have you found anything new on this? You mentioned the calcium channel above but have you thought about using a calcium channel blocker instead of blocking the NMDA receptors? I haven't spoken to my DAN about it yet and I am not sure if that medically & scientifically makes sense but I'm interested in a trial. (i.e., Amlodipine)

FatherOf2
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Re: Namenda response

Postby FatherOf2 » Fri Jun 13, 2014 12:42 am

alexsdad wrote:FatherOf2 - Have you found anything new on this? You mentioned the calcium channel above but have you thought about using a calcium channel blocker instead of blocking the NMDA receptors? I haven't spoken to my DAN about it yet and I am not sure if that medically & scientifically makes sense but I'm interested in a trial. (i.e., Amlodipine)

Blocking sodium channels looks interesting. Many AED do that. Amlodipine also looks interesting. My son is currently taking Namenda, Galantamine and Tenex. Namenda and Tenex help with hyperactivity and impulsivity. Galantamine helps with focus and language. Every time we start Galantamine after 1 month of break, it has a wow effect: teachers and therapists give raving reviews of my son. Unfortunately, the effect lasts only 2 weeks.

I am currently looking at dopamine pathways. It is interesting that people with social anxiety or ADHD have imbalanced neurotransmitters: low dopamine (results in poor focus and lack of motivation) and high norepinephrine (causes hyperactivity and impulsivity). There is a blood test to check these neurotransmitters, called plasma catecholamines. We haven't done it, but it is worth doing. One theory, which I like, explains this imbalance of dopamine and norepinephrine by poor function of the adrenal cortex. The adrenal cortex can be fatigued by a constant demand for cortisol production due to physical and emotional stress or due to a chronic inflammation. Release of cortisol is a healthy response of the body to a stress or inflammation. Cortisol increases glucose production and energy. But, if the adrenal cortex is fatigued or malfunctioning for some other reason, the adrenal medulla produces the excess of epinephrine (adrenaline) and norepinephrine (noradrenaline). Epinephrine increases the heart rate, and norepinephrine causes vasoconstriction (the narrowing of blood vessels), which results in high blood pressure. Both norepinephrine is synthesized from dopamine, which in turn is synthesized from tyrosine. So, the excess production of NE depletes dopamine and, thus, lowers motivation. Tenex (guanfacine) reduces NE, which takes care of the hyperactivity, impulsivity and insomnia. Dopamine is supposed to increase, but I don't see it in my son. So, I am looking at Focalin, which is a norepinephrine-dopamine reuptake inhibitor (NDRI), but I don't like its side effects. Another, more suitable approach, is to treat the chronic inflammation to reduce the demand for cortisol so that the body can properly sythesize it when it is needed in response to stress. This is what we are all trying to do here by treating possible causes of the chronic inflammation like bacterial infection (strep, PANDAS), food allergies, metal toxins, etc.

PS. I just learned that low cortisol levels correlate to low potassium levels. So, proper supplementation with potassium is good idea.

majadj
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Re: Namenda response

Postby majadj » Sat Aug 09, 2014 4:17 am

alexsdad wrote:FatherOf2 - Have you found anything new on this? You mentioned the calcium channel above but have you thought about using a calcium channel blocker instead of blocking the NMDA receptors? I haven't spoken to my DAN about it yet and I am not sure if that medically & scientifically makes sense but I'm interested in a trial. (i.e., Amlodipine)


Have you seen this?
http://epiphanyasd.blogspot.com/search/label/calcium

FatherOf2
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Re: Namenda response

Postby FatherOf2 » Fri Mar 06, 2015 10:14 am

I have been considering trying Namenda again to reduce stimming and hyperactivity, but then came across this site http://www.rxlist.com/namenda-drug/clinical-pharmacology.htm

"Memantine induced neuronal lesions (vacuolation and necrosis) in the multipolar and pyramidal cells in cortical layers III and IV of the posterior cingulate and retrosplenial neocortices in rats, similar to those which are known to occur in rodents administered other NMDA receptor antagonists. Lesions were seen after a single dose of memantine. In a study in which rats were given daily oral doses of memantine for 14 days, the no-effect dose for neuronal necrosis was 6 times the maximum recommended human dose of 20 mg/day on a mg/m² basis

In acute and repeat-dose neurotoxicity studies in female rats, oral administration of memantine and donepezil in combination resulted in increased incidence, severity, and distribution of neurodegeneration compared with memantine alone. The no-effect levels of the combination were associated with clinically relevant plasma memantine and donepezil exposures.

The relevance of these findings to humans is unknown."

Also more details here http://www.drugs.com/pro/namenda-xr.html

"In a juvenile animal study, male and female juvenile rats were administered memantine (15, 30, and 45 mg/kg/day) starting on postnatal day (PND) 14 through PND 70. Body weights were reduced at 45 mg/kg/day. Delays in sexual maturation were noted in male and female rats at doses ≥ 30 mg/kg/day. Memantine induced neuronal lesions in several areas of the brain on PND 15 and 17 at doses ≥ 30 mg/kg/day. Behavioral toxicity (decrease percent of auditory startle habituation) was noted for animals in the 45 mg/kg/day dose group. The 15 mg/kg/day dose was considered the No-Observed-Adverse-Effect-Level (NOAEL) for this study.

In a second juvenile rat toxicity study, male and female juvenile rats were administered memantine (1, 3, 8, 15, 30, and 45 mg/kg/day) starting on postnatal day (PND) 7 through PND 70. Due to early memantine-related mortality, the 30 and 45 mg/kg/day dose groups were terminated without further evaluation. Memantine induced apoptosis or neuronal degeneration in several areas of the brain on PND 8, 10, and 17 at a dose of 15 mg/kg/day. The NOAEL for apoptosis and neuronal degeneration was 8 mg/kg/day. Behavioral toxicity (effects on motor activity, auditory startle habituation, and learning and memory) was noted at doses ≥ 3 mg/kg/day during treatment, but was not seen after drug discontinuation. Therefore, the 1 mg/kg/day dose was considered the NOAEL for the neurobehavioral effect in this study."

luis
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Re: Namenda response

Postby luis » Wed May 24, 2017 5:03 pm

Bump.
Fo2, is your son still on Namenda ? My son is almost 17 and for the last 2 years we have been struggling against violent behaviors, coinciding with adolescence.
I suspected and confirmed that testosterone increases glutamate excitotoxicity (I can find the link if it interests anyone).
From one side there is that Theory of autistics being the super-male, excessive testosterone etc.
From other side, there is the 2012 Bumetanide study, that is still increasing in importance, with double blind/placebo tests being done all over the world, including China, very recently. Excess intracellular chlorine inverting GABA's funtion, from inhibitory to excitatory.
My son is on Bumetanide, and I was thinking if now would it be a good time to try Namenda again.
Only brainstorming: maybe Namenda's effect didn't fix because of excessive chlorine in neurons ? Maybe combining Namenda with Bumetanide could be good ? Maybe trying to reduce testosterone (with inositol and flaxseed powder) could help even more ?
Maybe avoiding supplements that increase glutamate, like B12, and taking others that help to reduce it, like lithium, could help even more ?

I would appreciate others thinking about this (not only Fo2), please.
Maybe we can help each other here exchanging our thoughts.

Thank you.

Nikkie111
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Re: Namenda response

Postby Nikkie111 » Thu May 25, 2017 8:50 am

luis wrote:Bump.
Fo2, is your son still on Namenda ? My son is almost 17 and for the last 2 years we have been struggling against violent behaviors, coinciding with adolescence.
I suspected and confirmed that testosterone increases glutamate excitotoxicity (I can find the link if it interests anyone).
From one side there is that Theory of autistics being the super-male, excessive testosterone etc.
From other side, there is the 2012 Bumetanide study, that is still increasing in importance, with double blind/placebo tests being done all over the world, including China, very recently. Excess intracellular chlorine inverting GABA's funtion, from inhibitory to excitatory.
My son is on Bumetanide, and I was thinking if now would it be a good time to try Namenda again.
Only brainstorming: maybe Namenda's effect didn't fix because of excessive chlorine in neurons ? Maybe combining Namenda with Bumetanide could be good ? Maybe trying to reduce testosterone (with inositol and flaxseed powder) could help even more ?
Maybe avoiding supplements that increase glutamate, like B12, and taking others that help to reduce it, like lithium, could help even more ?

I would appreciate others thinking about this (not only Fo2), please.
Maybe we can help each other here exchanging our thoughts.

Thank you.

But how do you know the behaviour is from high glutamate and not something else?

Didn't know about the b12 link I thought only excess folate does this ...


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