57 replies to this topic

[Flex]

I wanted to share with You this findings and at the same time ask about any thoughts

i.e. are there some reasons that this wont work & etc. ?

 

Here the findings:

 

Angiotensin II receptor blockers differentially affect CYP11B2 expression in human adrenal H295R cells.

Among transcription factors involved in the element, telmisartan significantly induced NGFIB/NURR1 expression.         [*]

KN-93, a CaMK inhibitor, abrogated the telmisartan-mediated increase of CYP11B2 transcription/mRNA expression and NURR1 mRNA expression, but not NGFIB mRNA expression.

http://www.ncbi.nlm....pubmed/24333837

 

Telmisartan attenuates MPTP induced dopaminergic degeneration and motor dysfunction through regulation of α-synuclein and neurotrophic factors (BDNF and GDNF) expression in C57BL/6J mice

 

Telmisartan (TEL), an angiotensin type 1 receptor (AT1R) antagonist, has been reported to exert neuroprotective effect in animal models of Parkinson's disease (PD). However, its effect on motor functions, mutant protein α-synuclein (SYN) and neurotrophic factors (BDNF and GDNF) expression and their interrelation in PD has not yet been elucidated. In the present study, the effect of TEL on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced motor dysfunctions and dopaminergic degeneration was ascertained through investigating the alterations in protein expression of dopamine transporter (DAT), tyrosine hydroxylase (TH) and SYN in C57BL/6J mouse. Further, the role of TEL on the gene expression of neurotrophic factors such as BDNF and GDNF and protein expression of vesicular monoamine transporter 2 (VMAT2) and Glial fibrillary acidic proteins (GFAP) were studied. In TEL treated mouse, strong negative correlation was observed between motor function and SYN, while a strong positive correlation was noted with BDNF and GDNF expression. TEL caused down-regulation of SYN, GFAP and up-regulation of DAT, TH, VAMT2, BDNF and GDNF expressions. Present data suggest that brain renin angiotensin system (RAS) plays a crucial role in motor function and in the regulation of key proteins such as SYN, BDNF and GDNF, DAT, TH, VMAT2 and GFAP in Parkinsonism. In conclusion, the present study shows that angiotensin type 1 receptor antagonists can ameliorate motor dysfunction and act as potential neuroprotective agent in the management of Parkinsonism.

http://www.pubfacts....hrough-regulati

 

[*]

Nurr1 regulates RET expression in dopamine neurons of adult rat midbrain

http://www.ncbi.nlm....pubmed/20533997

 

RET seems to be a target of GDNF

http://en.wikipedia...._proto-oncogene

 

Btw I´ve found that DJ-1 is also upregulating Vmat2

DJ-1 protects against dopamine toxicity: implications for Parkinson's disease and aging.

http://www.ncbi.nlm....pubmed/22887838

 

And Sodium- or Natrium Benzoate ( alias Food perservative E211) activates it:

Sodium benzoate, a metabolite of cinnamon and a food additive, upregulates neuroprotective Parkinson disease protein DJ-1 in astrocytes and neurons.

http://www.ncbi.nlm....pubmed/21701815

 

What are You thoughts on E211. Will it Work if ingested ?

 

Edit:

Valproic acid does also increase Nurr1 ( and CDNF ) mRNA

Induction of neurotrophic and differentiation factors in neural stem cells by valproic acid.

http://www.ncbi.nlm....pubmed/24460582

Edited by Flex, 30 August 2014 - 12:10 AM.

[maxwatt]

Thank you for sharing these studies.  Neuroprotection for Telmisartan (Micardis) looks probable, the rest is plausible; seems to work in rodent models.  One question is concentration needed, and any adverse effects at higher doses than say the .1% by weight the FDA allows for sodium benzoate in foods.  Cats respond differently than rodents, and show adverse effects at doses rodents can handle.  Humans?  Caution is warranted. 

 

I've known for some time that Telmisartan is a selective PPAR-delta agonist, which improves mitochondrial function and glucose control; sort of like exercise in a pill.  That it potentially protects against neurodegeneration should be good news for those using it.

[Flex]

This is the problem.

I´m not able to read the study, since it has to be paid.

The only thing what pops in my mind is to use a other study, where they researched for a "relative" similair effect.

This is not really the best solution but I have no other ideas..

 

So, regarding to this study below, they had experienced effects with 5mg/Kg in rats.[*]

Using the Human equvalent calculation:

5mg/kg x (6/37) = 0,810810 mg/kg x 80Kg = 64,864 mg

This is regarding to Wiki, within the torerable dose. Which states 80mg to be the Maximum dosage

 

One important question remains:

Why didnt this Research result appear as a Groundbreaking News elsewhere (e.g. Parkinson news, MJ fox) ?

A researcher or other related Academics could be helpful to answer that

 

http://en.wikipedia....iki/Telmisartan

Calculation refference

http://www.longecity...ns/#entry677822

[*]

Non-hypotensive dose of telmisartan and nimodipine produced synergistic neuroprotective effect in cerebral ischemic model by attenuating brain cytokine levels

http://www.sciencedi...091305714000793

---------------------------------

Regarding NaBe:

 

Sodiumbenzoate is used as an Emergency-antidote for Hyperammonemia and is called Ucephan in the US.

http://www.klinikum....ent.9477.0.html

http://www.spitalpha...benzoat_inf.pdf

 

The first is from a German University hospital and the second is a Swiss hospital.

 

The German states:

Natriumbenzoat 250 mg/kg über 1-2 Std. i.v., dann 250-400 mg/kg 24 Std.

 

= Natriumbenzoate 250 mg/kg over 1-2 Hours i.v., then 250-400 mg/kg 24 Hours

 

Side-effects in English (presumably for the Dosage above):

http://www.drugs.com/cons/ucephan.html

http://www.drugs.com...de-effects.html

 

Edited by Flex, 30 August 2014 - 03:33 PM.

[crazepharmacist]

Interesting. Mine just arrived recently in the mail, for endurance purposes. Had no idea it's potential for cognitive enhancement. 

[Flex]

I suffer from Depressions caused by Ethylphenidate. Possible explanation: [*].

Dont ask me why does it only affects me, but I know that this was the cause and I´ve tried a lot of stuff for this depression.

Only mao-b inhibitors and a very few others do help.

 

So I´m searching Day and Night to repair and increase Dopamine transmission e.g. via Vmat2, Dat and the others posted above.....

 

[*]

Methylphenidate Exposure Induces Dopamine Neuron Loss and Activation of Microglia in the Basal Ganglia of Mice

...Unbiased gene screening employing Affymetrix GeneChip® HT MG-430 PM revealed changes in 115 and 54 genes in the substantia nigra (SN) of mice exposed to 1 mg/kg and 10 mg/kg MPH doses, respectively. Decreases in the mRNA levels of gdnf, dat1, vmat2, and th in the substantia nigra (SN) were observed with both acute and chronic dosing of 10 mg/kg MPH. We also found an increase in mRNA levels of the pro-inflammatory genes il-6 and tnf-α in the striatum, although these were seen only at an acute dose of 10 mg/kg and not following chronic dosing..

 

Therefore, my hope relies on something like this, Gastrodia elata or on Edaravone...

 

Edaravone guards dopamine neurons in a rotenone model for Parkinson's disease.

This abolishment was attributable at least partly to edaravone's inhibition of rotenone-induced reactive oxygen species production or apoptotic promoter Bax expression and its up-regulation of the vesicular monoamine transporter 2 (VMAT2) expression. Collectively, edaravone may provide novel clinical therapeutics for PD.

http://www.ncbi.nlm....pubmed/21677777

Edited by Flex, 30 August 2014 - 04:44 PM.

[Flex]

wow my first well researched

 

Interesting. Mine just arrived recently in the mail, for endurance purposes. Had no idea it's potential for cognitive enhancement. 

 

Anyway, I guess You could make a great contribution, if You post Your experiences.

Since it affects (only?) the mRNA I guess it "shouldnt" be noticed after a few hours, moreover in the next days or 1-2 weeks.. Dunno

 

So it could also turn out that it doesnt change anyhing, but You never know.

 

I have an Idea whom to ask about this abstract and therefore its effectiveness. I dont want to write it for now in the public,

but after the response. I expect the response in the next time or even in few days.

 

Btw, If someone is interrested: 9-Methyl-beta-carboline could (but I´m not sure) also increase those targets:

9-Methyl-beta-carboline up-regulates the appearance of differentiated dopaminergic neurones in primary mesencephalic culture.

http://www.ncbi.nlm....pubmed/17913302

 

...The number of differentiated dopaminergic neurones was significantly increased and a wide array of neurotrophic/transcription factors (Shh, Wnt1, Wnt5a, En1, En2, Nurr1, Pitx3) and marker genes (Th, Dat, Aldh1a1) decisive for dopaminergic differentiation was stimulated....

 

Wnt = increases the profilation of stemcells and/or Oligodendrocytes, but is also implicated in cancer. Also increased by Lithium

Shh = Sonic hedge hog is increased by Cerebrolysin and EGCG (?). It increases Angiogenesis and plays a role in synaptic functioning

 

Thread:

http://www.longecity...nergic-neurons/

Edited by Flex, 30 August 2014 - 08:12 PM.

[Area-1255]

Why not just take a natural ACE inhibitor stack; Rhodiola Rosea, Hawthorne and Ginger.

Plus Rhodiola is an adaptogen with MAO/COMT inhibiting activity....

 

RR Extract and effects on health Parameters.

 

http://www.ncbi.nlm....pubmed/19168123

http://www.ncbi.nlm....pubmed/16837437

http://www.ncbi.nlm....pubmed/16837438

 

 

Hawthorne

----------------------------

http://www.ncbi.nlm....les/PMC2754502/

http://www.sciencedi...304387809001151

http://www.aafp.org/.../0215/p465.html

Edited by Area-1255, 30 August 2014 - 08:01 PM.

[PhaQ]

I've experimented with Telmisartan a little bit for its PPAR effects. All the warnings say not to combine it with potassium for fear of hyperkalemia. When I took it, I stopped my potassium supplementation. It may have delayed deficiency by a day or two, but within about four days I was low on potassium. My palpitations came back and I was getting the occasional twitch of atrial fibrillation. I started taking my normal dose of potassium and everything went back to normal.

 

YMMV, but if you supplement potassium, its something to keep in mind.

[Flex]

If You are reffering to me: Nice, Thank You.

But I would have to take mao inhibitors for the rest of my life.

This is what I´m trying to prevent and not the root cause of the problem.

 

 

[Haray]

If You are reffering to me: Nice, Thank You.

But I would have to take mao inhibitors for the rest of my life.

This is what I´m trying to prevent and not the root cause of the problem.

 

what is the root cause?

[Flex]

 

If You are reffering to me: Nice, Thank You.

But I would have to take mao inhibitors for the rest of my life.

This is what I´m trying to prevent and not the root cause of the problem.

 

what is the root cause?

 

 

Loss of Dopamine.

Look above for my assumption:

Methylphenidate Exposure Induces Dopamine Neuron Loss and Activation of Microglia in the Basal Ganglia of Mice
 

[Flex]

Update:

 I dont got any response for my request about whether it would work in humans.

I will report whether it works, if I get it.

[Shorty]

I eagerly await your impressions on Telmisartan Flex. I'm especially interested in its effects on physical endurance.

 

Just stay away from valproic acid. Ingestion of it has been shown to correlate with a lower verbal IQ in the children of pregnant mothers.

http://www.ncbi.nlm....pubmed/16454531

[Metagene]

Unless Flex is pregnant I don't think he has that to worry about.

[Flex]

Come on, I guess Shorty just wanted to point out that Valproic acid isnt that healthy.

Papers are nice, but using the stuff is something different.

 

I will keep You updated when I get it.

[Metagene]

I completely agree with that its just valproic acid would be on a long list of drugs to avoid If I (err) were having a baby. No offense to Shorty.

[Shorty]

None taken. I don't know Flex's gender but I suppose there is a reasonable albeit low chance that Flex is female and currently pregnant  

[APBT]

This is the problem.

I´m not able to read the study, since it has to be paid.

 

Here’s the FULL TEXT of Angiotensin II receptor blockers differentially affect CYP11B2 expression in human adrenal H295R cells

 

If you need other studies, post your request and I'll see if I can access them.  

Edited by APBT, 04 September 2014 - 03:34 AM.

[Flex]

wow thanks APBT

I know that You cant buy anything from a simple thank You.

But, at least, I want to let You know that this helps much and I really appreciate this. 

 

It made me wonder when I´ve read that the increase of Nurr1 lasted only ~1 hour

But the explanation seems to solve this in a (supposedly) good way:

However, the increase of NURR1 (an arrow in the upper panel of Fig. 6D) was not prominent most likely due to its original abundance in H295R cells.

 

Nevetheless this is one of the things were an academic could be helpful.

I´m playing with the thought to post something like this on reddit, but I´m affraid whether this would be even noticed by experts or properly answered.

 

Thanks to APBT it is possible to tell that, Telmisartan can increase Nurr1 up to 6 fold within chronic dosage (10mu mol/L)

 

See: figure 6

and:

 

When 80 mg of telmisartan was orally administrated to
Japanese hypertensive patients, its maximum serum concentration
increased approximately to 1 lmol/L (Ogihara et al., 2002). Since
telmisartan is known to be highly lipophilic and is easily to penetrate
into tissues and organs (Takai et al., 2005), it is possible that
local concentration of telmisartan may increase approximately to
10 lmol/L due to its accumulation.

 

@ APBT

Could You, if possible, post or PM this one too:

http://www.ncbi.nlm....pubmed/23747572

 

Edited by Flex, 04 September 2014 - 09:57 PM.

[APBT]

@ APBT

Could You, if possible, post or PM this one too:

http://www.ncbi.nlm....pubmed/23747572

 

Here’s the FULL TEXT link for Telmisartan attenuates MPTP induced dopaminergic degeneration and motor dysfunction through regulation of α-synuclein and neurotrophic factors (BDNF and GDNF) expression in C57BL/6J mice

[medievil]

Its the solution for anything related to brain inflammation, obsesity, aging, mental health and alot more.

[Flex]

From my humble knowledge, seemingly to sustain and perhaps increase mental claritiy.

Also for post-inflammation/damage, recover and aging.

 

Other way arround: If You use something against aging & etc. it would´nt increase automatically those targets. So maybe yes or maybe not

Therefore, You would´nt reach the same effect.

[medievil]

It does do everyhing you want for everyone mate, its a fucking miracle med

[Area-1255]

It does do everyhing you want for everyone mate, its a fucking miracle med

What about NSI-89? 

Edited by Area-1255, 19 September 2014 - 03:01 PM.

[medievil]

havent researched that one dont have a clue.

telmisartan also makes it impossible to get overweight no matter what you eat, its a mirac;e med

[elemerendero1]

as well as medievil says this is a great drug ... rather it is a miracle drug class. There are many researches done on angiotensin antagonists, both humans and his mice. try searching for "angiotensin antagonist" and memory, cognition, lifespan, anxiety, depression, stress, cortisol, ACTH, igf-i ... you'll find beautiful things. some drugs in this class, however, have reported negative effects on mood right (from memory ... I read a study a few years ago), but in any case it seems to me that telmisartan, losartan and candesartan (the latter as I recall is that most studied for nootropic effect and increased muscle mass) are ok.

if you search there should also be some post of medievil several years ago in this forum and on others (I think it was called at the time crazymeds)

[normalizing]

how do you get this med anyway, its not a popular one and its RX.

[Flex]

It does do everyhing you want for everyone mate, its a fucking miracle med

 

Have You taken Your "Alpha" meds ?

Are they working ?

 

Edit:

What a great "Thank You" for the posts and suggestions that I´ve written to You.

 

 

 

 

Edited by Flex, 19 September 2014 - 10:04 PM.

[Area-1255]

 

It does do everyhing you want for everyone mate, its a fucking miracle med

 

Have You taken Your "Alpha" meds ?

Are they working ?

 

Masteron bro. lmao

[medievil]

 

It does do everyhing you want for everyone mate, its a fucking miracle med

 

Have You taken Your "Alpha" meds ?

Are they working ?

 

Edit:

What a great "Thank You" for the posts and suggestions that I´ve written to You.

 

Is that sarcasm? as i do really apreciate mate thats why i send you a pm in the first place.