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taking new med for shingles nerve pain, cognition improved
alz+
Posted: Thursday, February 2, 2017 2:23 PM
Joined: 9/12/2013
Posts: 3608


Gabapentin 100 mg (usual first dose 500 - 1000 mg)

went to walk in clinic, a young doctor from India examined me.

Maybe I already posted this? Have return breakout of shingles and had stopped urinating.

In 5 minutes his questions reminded me I had been spraying the heck out  of my back to stop itching. Spray contained Benadryl = low urine flow = everything that comes with  that.

He suggested this med at a very low dose for the nerve pain, it is an anti-seizure med. Put me to sleep last night, one pill, slept well, woke up thinking. I could not believe it!

had forgotten my oil last night. I did more today than in a year, sorted clothes for trip to my Mom's funeral, did 2 loads of wash, remade bed in guest room for my daughter, cleaned upstairs bathroom, packed a suitcase (2 weeks ago it took me 3 days to pack for a short trip).

I was able to answer emails, paid bills online - and the kicker is the low dose has eliminated most of the nerve pain.

Anyone else take this? Anyone see any reason for this to act like Aricept?

would like a post of accidentally beneficial things people have come across. 

The doctor listened and wanted to know if anything else was off besides the shingles and urination stuff. His questions made me look at some things differently. and when he suggested this drug, which I never heard of, I said "That's good for ALZ."

He said he had never heard that before and I said I "hadn't either" and we laughed.

I hate going to doctors and meds - what the heck? I will take second pill tonight.

Was dreading the drive and the funeral and the lunch commotion traffic staying new place etc. now I am looking forward to it.

got my spelling mojo back for today too. weird!!! lucky I got shingles!

 also:

shingles vaccinations: he said "No one should get a shingles vaccination if they have had it in 5 years time," and that "having shingles is the best protection for further outbreaks," and that likely I had beaten the recent outbreak but the stress of mother dying had lowered my immune system.

so do NOT get vaccinated if you have had shingles in last 5 years



julielarson
Posted: Thursday, February 2, 2017 2:57 PM
Joined: 9/30/2015
Posts: 1155


Alz, I am on gabapentin but I have not noticed any changes in cognition or other areas of function. I did post a link to a study about the effects of it on one of the dementias but I can n ot remember for the life of me which one. Oh yes I remember it was for behavior problems with dementia.
Iris L.
Posted: Thursday, February 2, 2017 3:59 PM
Joined: 12/15/2011
Posts: 18520


I'm glad it is working for you, Alz+. 


I was on gabapentin for fibromyalgia-like pain all over my body, but it interfered with my vision so much that I could not see well enough to drive safely.  So I stopped the gabapentin.  It was great for the pain while I was on it.

I have had spurts when I seemed suddenly normal.  First was on thyroid med, then on CPAP.  But it didn't last.

It's great that you're getting things done.  Hurray for you!

 

Iris L.

The_Sun_Still_Rises
Posted: Thursday, February 2, 2017 4:22 PM
Joined: 7/24/2015
Posts: 3020


I hesitate post on this as my views tend be VERY different from everyone elses....but I know you tend have bad reactions meds....so here what I know:

20 years ago Neurontin aka Gabapentin was marketed as a bipolar drug as a mood stabilizer....that is what it was FIRST marketed as.  It was considered in the new class drugs as Lithium was the old drug used.   Mood stablizers are the STRONGEST of those meds that there are

Later on, as the rise of the battle against opiates for pain killers....they began (around 10 years ago??) marketing Gabapentin as a pain killer, yet mechanically it have no thing do with pain.  However, it became the medical industry "belief" that chronic pain...is not true pain, but rather a faulty re-looping of a nerve.  Like, you stub you toe, and the nerve tell you brain ouch....they think the nerve get stuck on "on" so that you keep feeling pain when there no reason feel pain (psychiatric)...rather than check if you broke toe.

They also widely rx this in Fibromyalgia which a pain syndrome...and the common complaint from people with that dx, is that their doctors keep treat them like a mental health patient. 

I was given it years ago for panic attacks...I was on it 4 days, I don't think I slept and I swear you I lived 6 months in that 4 days...it was, in my experience, 100x stronger than LSD.  I was in California then, and they have you call the poison center (creepy) and they tell me no only do it seem like I having a "toxic" reaction...but....that I can no JUST stop it, but that you have taper off it.   Apparently, it take place of something you body makes...and so you body stop make it.  So the fact that it can no be just stopped is something consider. 

I am VERY concerned about the RE-MARKETING it under different classes...and that a huge red-flag me.  But....that just me. 

I always recommend read the INSERT...you may have ask dr for copy (but definitely ask pharmacy - not just the generic print out that they give you).  Also ask doctor (he HAVE tell you) whether he gets a kick back from the pharmaceutical for rx'ing it. 

Here the link:

https://www.drugs.com/drug-interactions/gabapentin.html

Please let us know how it goes and what you choose do.

<3

 


BlueSkies
Posted: Friday, February 3, 2017 12:54 AM
Joined: 2/24/2016
Posts: 1096


Wow Alz, how interesting.  I bet it feels good to have all those capabilities back.  The drug sounds scary to me, but I sure would enjoy being a little more like the old me again.  Let us know if it continues to help you like that.  So interesting....
llee08032
Posted: Friday, February 3, 2017 7:26 AM
Joined: 5/20/2014
Posts: 4408


Neurontin (to the best of my knowledge) was first used as an anticonvulsant/anti seizure medication then later prescribed for mood stabilization and then pain. It is unlike Lithium which is an alkali metal that conducts the flow of salt (sodium) in the body. Neurontin is an gamma-aminobutyric acid. 
llee08032
Posted: Saturday, February 4, 2017 9:04 AM
Joined: 5/20/2014
Posts: 4408


Alz+,

Forgot to thank you for sharing info about shingles vaccination. I have been trying to pay attention to stress levels and take antiviral so shingles is less severe. There is a correlation between my stress level and an outbreak. When I'm stressed I can feel the burn prior to the outbreak. Hate the antivirals and do not take opiates for pain because they are so addictive. Will pray that all goes well for you.


Lane Simonian
Posted: Saturday, February 4, 2017 2:07 PM
Joined: 12/12/2011
Posts: 5161


Gabapentin appears to be a NMDA receptor antagonists (Namenda is another NMDA receptor antagonist).  I am not sure how good a NMDA receptor antagonist is is though.

These findings suggest that the inhibitory effect of GBP on NMDA receptors may play an important role in the antinociceptive ("pain-killing") property of GBP...

Inhibiting the pathway that leads from NMDA receptor activation to nitro-oxidative stress, removing oxidants, and repairing part of the damage they do to the brain is likely the key to treating Alzheimer's disease.

We suggest that oxidative stress mediated through NMDAR and their interaction with other molecules might be a driving force for tau hyperphosphorylation and synapse dysfunction. Thus, understanding the oxidative stress mechanism and degenerating synapses is crucial for the development of therapeutic strategies designed to prevent AD pathogenesis.

Continue to improve alz+.


The_Sun_Still_Rises
Posted: Saturday, February 4, 2017 2:17 PM
Joined: 7/24/2015
Posts: 3020


Sorry Lane....I thought I had posted from the Wiki...but I must have imagined it....

"Gabapentin was initially synthesized to mimic the chemical structure of the neurotransmitter gamma-aminobutyric acid (GABA), but is believed to act on different brain receptors."

"Some of its activity may involve interaction with voltage-gated calcium channels. Gabapentin binds to the subunit (1 and 2) and has been found to reduce calcium currents after chronic but not acute application via an effect on trafficking of voltage-dependent calcium channels in the central nervous system.  Another possible mechanism of action is that gabapentin halts the formation of new synapses."

"Other neurophysiological findings indicate that gabapentin also interacts with NMDA receptors, protein kinase C, and inflammatory cytokines."

 

"The NMDA receptor is very important for controlling synaptic plasticity and memory function."

<3


The_Sun_Still_Rises
Posted: Saturday, February 4, 2017 2:30 PM
Joined: 7/24/2015
Posts: 3020


IF it acts as GABA....it important know that GABA and Glutamate play an important dance gether....GABA shuts "off" activity, whereas Glutamate turns it "on".....

<3


Lane Simonian
Posted: Saturday, February 4, 2017 2:52 PM
Joined: 12/12/2011
Posts: 5161


Thanks for the addition, Sun.  I was going to add that I too am uneasy about the off label use of medications.

I am not quite sure how similar the effects of gabapentin are to GABA.  One study suggested that it does not significantly reduce glutamate levels.  Its main action is likely through inhibiting NMDA receptor activation.

Protective effect of gabapentin on N-methyl-D-aspartate-induced excitotoxicity in rat hippocampal CA1 neurons.

Gabapentin was developed as an anticonvulsant, but has also been used to alleviate hyperalgesia in neuropathic pain. In this study, the protective effect of gabapentin against N-methyl-D-aspartate (NMDA)-induced excitotoxicity in rat hippocampal CA1 neurons was investigated. Pre-treatment with gabapentin reduced the degree of neuronal damage induced by NMDA exposure in cultured hippocampal slices. Patch-clamp studies revealed that gabapentin significantly inhibited the NMDA receptor-activated ion current in dissociated hippocampal CA1 neurons, resulting in suppression of glutamate-induced neuronal injury. These results show that gabapentin may exert protective effects against glutamate-induced neuronal injury at least in part by inhibiting the NMDA receptor-activated ion current.

 

Compare this to eugenol in various essential oils via aromatherapy (although these oils can be overstimulating for some people), ferulic acid (in panax ginseng and Feru-guard) and CBD oil--all of which can improve cognition in people with Alzheimer's disease. 

 

 1997 Apr 4;225(2):93-6.

Eugenol protects neuronal cells from excitotoxic and oxidative injury in primary cortical cultures.

Abstract

 

We examined the neuroprotective efficacy of eugenol against N-methyl-D-aspartate (NMDA)-, oxygen-glucose deprivation-, and xanthine/xanthine oxidase-induced neurotoxicity in primary murine cortical cultures. Eugenol (100-300 microM) attenuated NMDA (300 microM)-induced acute neurotoxicity by 20-60%. At the same concentration range, eugenol also inhibited NMDA (300 microM)-induced elevation in neuronal 45Ca2+ uptake by 10-30%. In the oxygen-glucose deprivation (50 min) neurotoxicity, eugenol (100-300 microM) prevented acute neuronal swelling and reduced neuronal death by 45-60% in a concentration-dependent fashion. Oxidative neuronal injury induced by xanthine/xanthine oxidase was also significantly reduced (75-90%) by eugenol (100- 300 microM) addition. These results suggest that eugenol may play a protective role against ischemic injury by modulating both NMDA receptor and superoxide radical.

 

Potent protection of ferulic acid against excitotoxic effects of maternal intragastric administration of monosodium glutamate at a late stage of pregnancy on developing mouse fetal brain.

 

Neuroprotective effect of (-)Delta9-tetrahydrocannabinol and cannabidiol in N-methyl-D-aspartate-induced retinal neurotoxicity: involvement of peroxynitrite.

The neuroprotection by THC and CBD was because of attenuation of peroxynitrite. 

 

This link is to a chart that has helped me picture the pathway toward Alzheimer's disease (ONOO- is peroxynitrite).

http://www.frontiersin.org/files/Articles/131867/fncel-09-00091-HTML/image_m/fncel-09-00091-g003.jpg




Lane Simonian
Posted: Saturday, February 4, 2017 8:19 PM
Joined: 12/12/2011
Posts: 5161


This is an interesting study on gabapentin for dementia:

Table 1 demonstrates a significant difference in MMSE scores before and after gabapentin treatment. These were all completed by an independent psychologist. All of the subjects demonstrated an improvement.

Table 2 demonstrates a positive difference between pre- and posttreatment scores for affective lability, behavioral dyscontrol, cognitive impairment, depression, and psychotic symptoms. These findings, though not placebo controlled, suggest that gabapentin at least temporarily improved cognitive, emotional, and behavioral functioning in patients with dementia.

http://primarypsychiatry.com/gabapentin-in-the-treatment-of-alzheimeras-disease-and-other-dementias/

A safe dose for dementia might be lower than for other conditions.

When gabapentin was slowly titrated to dosages lower than generally utilized for the treatment of chronic pain or bipolar illness, it appeared to be well tolerated with minimal transient side effects. 


The_Sun_Still_Rises
Posted: Sunday, February 5, 2017 7:23 AM
Joined: 7/24/2015
Posts: 3020


Interesting.  The drug scares me because I had such a bad reaction it.  And Canada111 I think just posted her bad reaction. 

I have a GABA/Glutamate imbalance as I overmake Glutamate....so I found it interesting that Gabapentin is a mimic of GABA (but despite being synthetic GABA, doesn't act like GABA).

However, bottom line for me....is rather than affect the GABA receptor, it affects the NMDA receptor (The receptor in ALZ)....and GABA's affect is an "off switch" whereas glutamate is an "on switch" 

This again proves my point that they giving it for pain NOT because it have ANY mecanichs in pain....but because they think a "pain syndrome" is a mental health issue. 

I would be scared as heck anything that mess with the NMDA receptor shut it off. 

Gabapentin has been used for literally EVERYTHING under the sun since it was made...and have failed in all its uses. 

That said....we will have wait for Alz+ say how it works for her. 

<3


Lane Simonian
Posted: Sunday, February 5, 2017 11:15 AM
Joined: 12/12/2011
Posts: 5161


This is a very careful and good assessment, Sun.  I think there are safer and more effective treatments that interfere with the NMDA receptor activation--oxidant pathway, but I will be curious too regarding further reports from alz+.
alz+
Posted: Wednesday, February 8, 2017 12:33 PM
Joined: 9/12/2013
Posts: 3608


Thank you all for such  detailed information.

Llee - I also can feel the heat  and burn when stressed and know here comes shingles.

The doctor at walk-in clinic thought I was having small contained blisters because previous attacks increase immunity - but maybe for us with dementia we are triggered by stress in particular.

****

The effects remain that I am physically up and about. It reduces the itching from shingles, and the dreaded anti-viral medication is done today. I also put some drawing salve on shingles, it dried them out in 24 hours.

The doctor said I must see my regular doctor to use the Gaba stuff after shingle pain/itch is gone. 

*****

my question or inquiry is about the assumption that Alzheimer's is a progressive unretrievable degeneration. If using CBD oil brings back my cognitive abilities within minutes (not pre illness levels but huge to me) and the FREEZE physical slowed physicality is overcome by a pill (I walked a mile in snow 2 days ago, attended my mother's funeral, attended a wake, cleaned up the house we used, etc etc) and will swim today - then is this helpful to someone figuring out a treatment if not a cure?

Are these not clues to a different concept of Alzheimer's?



alz+
Posted: Wednesday, February 8, 2017 12:46 PM
Joined: 9/12/2013
Posts: 3608


Julie - behavioral problems? I was much more cooperative and felt less threatened through this past week while taking Gaba.

My daughter came for my Mom's / her grandma's funeral. I had to clean the bedroom upstairs and bathroom and usually get really nervous about anyone coming to the house.

We had a 5 hours drive down there, and back usually hard on me. I did better. I let myself (or was somehow able to) relax around 40 people during the wake dinner. I was hugged my nephews and nieces I have not seen in 10 years. Everyone was talking around me with music and drinks being served.

I had excellent help from Keeper and my daughter - my behavior in this kind of setting is often tense enough for us to just avoid it.

Does this seem like how it helps you? Lowers the angry reaction bar, more patience, more cheerful?

*****

NOTE:  Thank you to all who helped me get myself motivated to visit my Mother before her death. It  was a visit that made everything possible. She died in her sleep. There was no tension between anyone during the funeral and after. I feel clean and whole.

No one in my family has ever said anything sympathetic or supportive about my having Alzheimer's, my Mother never mentioned it. I finally understand they don't owe me anything emotionally, I feel stronger letting go of all that pain.

love and courage



alz+
Posted: Wednesday, February 8, 2017 12:56 PM
Joined: 9/12/2013
Posts: 3608


Sun -i had checked drugs.com but used your link to check for side effects and found this:

*Feeling extra happy

*Increased physical activity

among many others. My dose is 100MG because the doctor understood and believed me on the micro doses that work in my body.

Now do I care if I am having the side effect of being unusually UP and able to walk the dog and clean up alittle?  !!!

For first time am I taking a med FOR the side effects?! Ha!

love and courage to challenge the idea of dementia



julielarson
Posted: Wednesday, February 8, 2017 1:17 PM
Joined: 9/30/2015
Posts: 1155


Alz, I really do not know how it affects me other than it takes away a pain I had in my left leg. That is what it was prescribed for..
jfkoc
Posted: Wednesday, February 8, 2017 1:39 PM
Joined: 12/4/2011
Posts: 21250


Alz+...how wonderful it all went well.

My husband was on Gabapentin. I looked back at the information I had re this drug and found this discussion on alzconnected.

I post only as additional information....I had not read it recently.

 https://www.alzconnected.org/archive.aspx?g=posts&t=26658


Jo C.
Posted: Wednesday, February 8, 2017 3:16 PM
Joined: 12/9/2011
Posts: 13612


Dear alz+, I am so delighted for you in that your experience with your mother's funeral and the dinner went so well . . . . that is truly awesome.  I kept reading to see how things went and this is really good news.  Hurray for Mr. Keeper and your daughter too.

I am also very happy for the positives you are receiving from your med.   It seems like an unexpected gift.   What a difference it must be to feel the shiny changes on the postive side of the ledger.

Big hug coming to you,

J.


The_Sun_Still_Rises
Posted: Wednesday, February 8, 2017 4:28 PM
Joined: 7/24/2015
Posts: 3020


I am sooo glad for you that you got some much needed boost of happiness in a dark time.   Thanks for sharing you experience it.   And you had yet another nice visit you daughter, and that everyone relatively good.   

I am, however, very sorry that you family did no embrace you and surround you in love when you dx'd. 

<3


Marta
Posted: Wednesday, February 8, 2017 5:28 PM
Joined: 6/3/2013
Posts: 1250


Lane:  who is "we" as in "we suggest?"
BlueSkies
Posted: Wednesday, February 8, 2017 5:46 PM
Joined: 2/24/2016
Posts: 1096


Alz, so glad to hear you are still reaping benefits from drug side effects.  Who would have thought.  Go figure!  
Lane Simonian
Posted: Wednesday, February 8, 2017 11:28 PM
Joined: 12/12/2011
Posts: 5161


Marta, here is the article title and the name of the researchers.

Mechanism of Oxidative Stress and Synapse Dysfunction in the Pathogenesis of Alzheimer’s Disease: Understanding the Therapeutics Strategies

 

One question to begin with is whether gabapentin is a better NMDA receptor antagonist than Namenda.  

Here is the chart again that links NMDA receptor activation with peroxynitrite (ONOO-). Intervention anywhere along that pathway may help in the treatment of Alzheimer's disease.

http://www.frontiersin.org/files/Articles/131867/fncel-09-00091-HTML/image_m/fncel-09-00091-g003.jpg

The answers are there; most people just are not looking in the right places.  Keep looking for answers, alz+.


llee08032
Posted: Thursday, February 9, 2017 5:36 AM
Joined: 5/20/2014
Posts: 4408


"Feeling extra happy and increased physical activity!" Well I just love these side effects for you Alz+. I'm glad all went well with the funeral and the trip. Love you!
alz+
Posted: Thursday, February 9, 2017 8:51 AM
Joined: 9/12/2013
Posts: 3608


thank you all for you endless support and information.

what would we be doing if we did not have eachother here to figure stuff out?

One thing on CBD oil - I think the syringe type tube it comes in cost $500.  That was for either thc or not thc. It felt awfully expensive but I am on month 6 of it taking it twice a day. So worth it!

The gaba med - will ask my doctor this month what she thinks and if I can continue the 100 mg dose. The usual dose is 300mg - 1000+ mg!

I wonder how many "bad reactions" to drugs are because the dose is too high? remember a report that found elderly (over 60), people with chronic illness, and women esp past menopause benefit from 50% or more lower dose than usual.

*******

the larger point in all my experimenting is : 

If symptoms can be virtually reversed in minutes, then the problem is not plaques and tangles but some kind of missing fuel or connection enhancer.

My belief is that we do not lose our memory but our ability to recall things fast enough to speak them. I suspect the current 7 stage view of Alz in particular makes people live like they are trying to find when they moved permanently down another notch.

I did also start a supplement at same time called NATTOKINASE which is from an enzyme in Japanese natto for "thick blood". Lack of physical activity caused my blood to thicken (dimer blood test) and this is usually taken by people with circulation problems. Normal dose is 2 capsules 3 times a day. I take 1 a day.

question authority! we will likely find treatment protocols that work before researchers and drug companies.


Iris L.
Posted: Thursday, February 9, 2017 11:08 AM
Joined: 12/15/2011
Posts: 18520


Alz+, that's why I call us Dementia Pioneers.  We are pioneers in finding out what helps us.  You are a great Dementia Pioneer!


Iris L.


alz+
Posted: Friday, February 10, 2017 9:14 AM
Joined: 9/12/2013
Posts: 3608


making appointment with regular doctor to see if I can continue with gaba pill at low dose.

Is this the same as Namenda? I had nightmares and shocks in my body from Namenda and quit right away - years ago.

I slept 9 hours last night after taking the pill and woke up almost pain free. what the heck?

The Apathy thing - Inertia - this plus the cbd oil = me moving more than before I was diagnosed.

If this is same as Namenda - and comes in such a low dose maybe it is safe to try for that "inability to begin" what I experience as a physical symptom of ALZ.

I think there is a physical experience, not just memory loss, which I also doubt is permanent.

It is a tension which is expressed in tight muscles, as if my body is holding me back from getting up and moving.

In Best practices we are advised to let our bodies move through exercise. Movement = health to a large degree no matter what age we are or what illness we have.

My trick is to make my body move AS IF it were relaxed, to change my shuffle into a normal walking gait. Also doing cross-crawl movements help a lot. I am taking an easy water exercise class and when we do opposite arm leg movements I would be all jumbled up. In my training as massage therapist in past life we were taught that when someone begins rehab and has difficulty doing a movement to be joyful about that difficulty because that is physical experience of brain relearning how to move naturally again.

****

yes I was hippie and at my mother's funeral my nephews celebrated the family's Only Flower Child! I did not know they appreciated the one lefty in the bunch so much!



julielarson
Posted: Friday, February 10, 2017 9:51 AM
Joined: 9/30/2015
Posts: 1155


Big smile!  I love you Alz!
Lane Simonian
Posted: Friday, February 10, 2017 9:58 AM
Joined: 12/12/2011
Posts: 5161


Gabapentin is not the same as Namenda, but they inhibit the same receptor (the NMDA receptor).  

Here are the side effects of each:

Gabapentin:

Commonly reported side effects of gabapentin include: ataxia, dizziness, drowsiness, fatigue, fever, nystagmus, sedation, and viral infection. 

Namenda:

Common side effects of Namenda

 

  • Fatigue, sleepiness, dizziness, confusion, insomnia
  • Headache, hallucinations, anxiety, depression, aggression
  • Digestive distress, diarrhea, constipation, stomach pain, nausea, vomiting
  • Cough, shortness of breath, bronchitis, flu-like symptoms, pneumonia
  • Weight gain
  • Back pain, body pain, arthritis-like symptoms
  • Urinary incontinence, urinary tract infection, frequent urination
  • Skin rash (this requires immediate medical attention as it could be life-threatening!)
  • Heart failure, chest pain, slow pulse, irregular heart rhythms
  • Anemia
  • There is some but not a complete overlap of symptoms and of course not everyone experiences theses symptoms.

Lane Simonian
Posted: Friday, February 10, 2017 10:11 AM
Joined: 12/12/2011
Posts: 5161


A low dose of gabapentin appears to produce few side effects in most people.

The larger issue is finding compounds that inhibit NMDA receptors or which scavenge peroxynitrite or which do both.

In conclusion, through this review, we have tried to give our perspective on the wide variety of interaction between NMDAR-mediated oxidative stresses with the etiology of Alzheimer’s disease. NMDAR-mediated oxidative stress mechanisms are likely to play an important role in the synapse dysfunction in the pathogenesis of AD. Moreover, mitochondrial-mediated oxidative stress and apoptosis are also suggested to be contributing factors in AD pathogenesis. Furthermore, oxidative stress-mediated kinase and tau phosphorylation provides a connection of synapse dysfunction in AD. As we are not getting complete remedies from antioxidant therapy or known NMDAR antagonist drug used for AD pathology, should we go for combinational therapy? Or are there so many intermediate molecules between NMDAR to neurodegeneration? Should we go for target intermediate molecules? Therefore, understanding the role of oxidative stress-associated molecule and kinases in synapse dysfunction during AD pathogenesis may also lead to the development of mechanism-based therapeutics and better constructive strategies.

The person who developed Namenda for Alzheimer's disease (Stuart Lipton) acknowledges that it does not work as well as it should (he is working on a new combination called nitro-memantine but no news on it yet).

Lipton's lab had previously discovered how a drug called memantine can be targeted to eNMDA (extrasynaptic) receptors to slow the hyperactivity seen in Alzheimer's. This patented work contributed to the FDA approval of memantine in 2003 for the treatment of moderate to severe Alzheimer's disease. However, memantine's effectiveness has been limited. The reason, the researchers found, was that memantine -- a positively charged molecule -- is repelled by a similar charge inside diseased neurons; therefore, memantine gets repelled from its intended eNMDA receptor target on the neuronal surface.

And for gabapentin:

These findings suggest that the inhibitory effect of GBP [gabapentin] on NMDA receptors may play an important role in the antinociceptive ["pain-killing"] property of GBP; however, it does not appear that GABA(A) and glycine receptors or GIRK channels contribute to the pharmacological properties of GBP.

Maybe this is enough for one post, I am going to add one more.


Lane Simonian
Posted: Friday, February 10, 2017 10:26 AM
Joined: 12/12/2011
Posts: 5161


Overactivation of the NMDA receptor leads to the activation of caspase 3.  Caspase 3 is a key enzyme in the initial formation of amyloid which latter aggregates into plaques and in the production of tau fragment which later form tangles.  Perhaps, more importantly the enzyme kills neurons.

http://www.frontiersin.org/files/Articles/131867/fncel-09-00091-HTML/image_m/fncel-09-00091-g003.jpg (ONOO- is peroxynitrite).

Various forms of amyloid contribute to NMDA receptor overactivation during the early stages of Alzheimer's disease but so do many other factors (air pollution, psychological stress, mercury, a diet high in sugar, carbohydrates, and salt, etc.).  And as the disease continues, amyloid no longer activates NMDA receptors.

A loop develops where NMDA receptor activation leads to peroxynitrite formation and caspase 3 activation and peroxynitrite formation inhibits the transport of glutamate which leads to more NMDA receptor activation.  If you inhibit NMDA receptor activation and remove peroxynitrite, you stop the loop which causes the disease and you begin to reverse the disease.  If beneficial treatments are stopped, the loop begins again.

These findings suggest that the inhibitory effect of GBP on NMDA receptors may play an important role in the antinociceptive property of GBP; however, it does not appear that GABA(A) and glycine receptors or GIRK channels contribute to the pharmacological properties of GBP.

The neuroprotection by THC and CBD was because of attenuation of peroxynitrite.


Lane Simonian
Posted: Friday, February 10, 2017 10:30 AM
Joined: 12/12/2011
Posts: 5161


Here is to all the good "old" lefties.