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low dose Russian antihistamine and Alzheimer's
alz+
Posted: Thursday, September 3, 2015 10:13 AM
Joined: 9/12/2013
Posts: 3549


http://www.wikimedz.com/topic/c2fb1f9bddeef4941da3845fbba5da36

I have been trying to find a link to evidence that low dose Benadryl reverses some Alzheimer's symptoms, posted by "David" on yoad ? and since these drugs were tested in 1961 it seems hard tofind anything that is not also mentioned by a "David" as below:

Q: A potential treatment


I have an acquired mitochondrial dysfunction with some symptoms similar to Alzheimer's.
I was researching a question about the use of antihistamines if one has a mitochondrial disease and came across Phizer's look at "Dimebond", a Russian antihistamine, for it's reported benefits in Alzheimer's.
The resolution of that trial seemed "funny" to me and I received some anecdotal evidence so I started low doses of diphenhydramine (Benadryl) daily hoping for cognitive improvement.
It works! My cognitive and memory problems are mostly resolved as long as I avoid stress. Additionally many of my physical problems (mostly fatigue related) have improved dramatically.
What I found to explain what I was seeing is a study published in 1961 that shows that low concentrations of certain antihistamines INHIBIT CELL DEATH! And Benadryl was the only one to provide "almost complete protection".
The most likely form of cell death in ageing and disease is "apoptosis". Do a search for "Alzheimer's and apoptosis" and you will see the connection.
Low Dose Benadryl:
1 mg per 30 to 50 lbs of body weight at meal and bedtimes (4 times per day).
You can get these low doses several ways:
1/4 of the adult tablet is 6.25 mg
1/4 of the children's tablet is 3.125 mg
1 ml of the children's liquid is 2.5 mg
Of course check for any interactions with other drugs and if you have a sodium channelopathy do not use Benadryl as it is an intra-cellular sodium channel blocker.
David

*********

Reactions have been already along lines that Benadryl is dangerous to ALZ.

But dosage is not mentioned. Any Medicine can become toxic at higher dose and poison can become medicine at low dose.

Looking for more help with this. Found lots of parents giving kids awful drugs for ADHD and wanting to use cannabis but being shouted down about the danger, while the approved drugs are causing hell in these kids!

will look for something better but thought some one might understand this possibility better than me.


alz+
Posted: Thursday, September 3, 2015 10:20 AM
Joined: 9/12/2013
Posts: 3549


http://ltcadministrator.com/aging/antihistamine-can-reverse-mental-deterioration/

Antihistamine Can Reverse Mental Deterioration

~ Zev Driller

An old antihistamine drug may come back on the market one day – to treat Alzheimer’s disease. Dimebond, once sold in Russia to treat allergies, may have the happy side affect of reversing cognitive decline. Test subjects taking Dimebond actually improved their scores on cognition tests, compared to both the control group and their own baseline scores. Alistair Burns, M.D., of the University of Manchester in England, and Robin Jacoby, D.M., of the University of Oxford in England, believe it attacks several mechanisms of dementia that could make it affective in treating mild to moderate Alzheimer’s disease.

Dimebond was only on the market temporarily, and in Russia. It was pulled when better, targeted antihistamines were introduced, making it superfluous. For that reason, it was never approved for use in the United States, and has not received much notice elsewhere.


alz+
Posted: Thursday, September 3, 2015 10:51 AM
Joined: 9/12/2013
Posts: 3549


Found other articles claiming trials were a failure and then, not so fast.

It would not have been a money maker. Zurich Univ claims it does work.

Comments on this Paper

  1. With the twin papers (one on AD and the other on α-synucleinopathy) in Mol. Psychiatry, Sam Gandy's lab revive the importance of Dimebon in amyloid disorders. Both these papers suggest a role of Dimebon in inducing autophagy and thereby ameliorating disease pathology. Elegant work that has implications for therapy.


Lane Simonian
Posted: Friday, September 4, 2015 1:11 PM
Joined: 12/12/2011
Posts: 4599


I am at a lost on this one. Most of the articles on this are old and dimebon was deemed a failure, but neither means there might not be something there. Preventing the death of neurons is one of the keys to treating Alzheimer's disease. But the extent to which low dose benadryl or dimebon does this is unclear. And it is possible that one or both helps with various forms of amnesia but not with Alzheimer's disease. Usually, I can find answers relatively easily, but this time I am just not coming up with anything that leads me in one direction or another.
skericheri
Posted: Friday, September 18, 2015 10:46 PM
Joined: 12/10/2011
Posts: 287


My Charlie was in the Dimebon trial. I believe that one of the reasons for discontinuing the trial was that not enough people were helped. Charlie was Slavic and he basically seemed to be holding until the trial was discontinued and his supply ran out. I was sorely disappointed.

Lane Simonian
Posted: Saturday, September 19, 2015 7:16 PM
Joined: 12/12/2011
Posts: 4599


I am going to post these as an interesting juxtaposition and maybe giving additional credence to individual response.

Dimebon

The antihistamine drug Dimebon was first used to treat allergies in Russia in the early 1980s. Recently, Dimebon has been proposed to be useful for treating neurodegenerative disorders [] (Fig. 2). Results of the first pivotal clinical trial of Dimebon in AD showed that this drug improved the clinical course of the disease []. In this randomized, double-blind, placebo-controlled trial of 183 patients with mild-to-moderate AD, patients treated with Dimebon experienced statistically significant improvements compared to placebo in all of the key aspects of the disease: memory and thinking, activities of daily living, behavior and overall function. After both 6 months and a full year of treatment, Dimebon-treated patients performed significantly better than placebo-treated patients in all key measures of the disease []. A phase III trial of Dimebon in AD treatment will soon be initiated. Dimebon also demonstrated efficacy in a phase II trial with HD patients conducted by Medivation and the Huntington Study Group (DIMOND). Despite extremely encouraging results in clinical trials, the mechanisms responsible for the beneficial actions of Dimebon remain poorly understood. Previous reports show that Dimebon is an inhibitor of NMDA receptors [] and voltage-gated Ca2+ channels [, ]. A previous study also showed that Dimebon blocks opening of the mitochondrial PTP induced by Aβ25–35 and MPP+ []. Together these studies suggest that the clinical benefits exerted by Dimebon may be due to its ability to stabilize neuronal Ca2+ homeostasis and mitochondrial function. Currently, the scientific community is actively investigating the mode of action of Dimebon in neurodegenerative diseases.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2790540/


Negative Phase III Trial Results for Dimebon (Latrepirdine)

The drug Dimebon (latrepirdine) was being used as an antihistamine in Europe when a researcher discovered that the treatment might be effective in treating Alzheimer’s disease. In the small trial that followed, the drug showed promise – and although the mechanism for the drug’s success was unknown, it stirred excitement and hope in the Alzheimer research community.

Unfortunately, in March of this year, the drug’s manufacturer Pfizer Inc., announced Dimebon did not meet either of its primary research targets in a late-stage clinical study, faring no better than a placebo at treating the disease. After six months of treatment, there was no significant difference between either drug group and the controls.


http://www.alz.org/norcal/in_my_community_19452.asp


The degree of NMDA receptor inhibition may determine whether a drug provides some limited improvement in activities of daily living, slows down the progression of Alzheimer's disease, or partially reverses it.


Eden Desjardins
Posted: Tuesday, September 22, 2015 10:58 AM
Joined: 5/25/2015
Posts: 48


Hi Lane,

From what I could find, the NMDA receptor is very important for controlling synaptic plasticity and memory function. Thus, the degree of its inhibition could result in either improved memory function or loss.

It's unfortunate that there were no differences between the control group and the drug group though.

Keep fighting,
Eden

Lane Simonian
Posted: Tuesday, September 22, 2015 11:41 AM
Joined: 12/12/2011
Posts: 4599


Yes, the NMDA receptor is involved in memory and synaptic plasticity and this appears to work through the neuroprotective phosphatidylinositol 3-kinase/Akt pathway.

http://www.ncbi.nlm.nih.gov/pubmed/12736339

Unfortunately this pathway is largely blocked in Alzheimer's disease. Instead, NMDA receptor activation leads to the activation of p38 MAPK and the formation of peroxynitrites. Thus, perhaps the reason behind studies which suggest that what increased intelligence in human beings made us one of the few animals susceptible to Alzheimer's disease.

Switching of N-methyl-D-aspartate (NMDA) receptor-favorite intracellular signal pathways from ERK1/2 protein to p38 mitogen-activated protein kinase leads to developmental changes in NMDA neurotoxicity.


http://www.ncbi.nlm.nih.gov/pubmed/21474451

2006 Sep;13(9):1506-14. Epub 2006 Jan 20.

Two distinct signaling pathways regulate peroxynitrite-induced apoptosis in PC12 cells.

Abstract

The mechanisms of peroxynitrite-induced apoptosis are not fully understood. We report here that peroxynitrite-induced apoptosis of PC12 cells requires the simultaneous activation of p38 and JNK MAP kinase, which in turn activates the intrinsic apoptotic pathway, as evidenced by Bax translocation to the mitochondria, cytochrome c release to the cytoplasm and activation of caspases, leading to cell death. Peroxynitrite induces inactivation of the Akt pathway. Furthermore, overexpression of constitutively active Akt inhibits both peroxynitrite-induced Bax translocation and cell death. Peroxynitrite-induced death was prevented by overexpression of Bcl-2 and by cyclosporin A, implicating the involvement of the intrinsic apoptotic pathway. Selective inhibition of mixed lineage kinase (MLK), p38 or JNK does not attenuate the decrease in Akt phosphorylation showing that inactivation of the Akt pathway occurs independently of the MLK/MAPK pathway. Together, these results reveal that peroxynitrite-induced activation of the intrinsic apoptotic pathway involves interactions with the MLK/MAPK and Akt signaling pathways.


Still, too much deactivation of NMDA receptors may be a problem in several forms of dementia, perhaps including some case of Alzheimer's disease.


I don't know how much any of this played in the failed phase three clinical trial for dimebon. My guess would be that it did not inhibit NMDA receptors enough rather than too much, but that is just a guess.


Thank you, Eden.