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"Cure depression in 3-4 days." - Study

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#1 Reformed-Redan

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Posted 19 March 2012 - 06:27 PM


Was looking around for strong NGF enchancers. Cam across something very promising:

7,8-Dihydroxyflavone and its Derivatives Useful for Treatment of Neurodegenerative Diseases




Applications

A compound for the treatment of various neurological diseases such as Alzheimer's, Huntington's, ALS, Rett syndrome, epilepsy, Parkinson's, spinal cord injury, stroke, ischemia, brain injury, diabetic neuropathy, peripheral neuropathy, dementia, peripheral nerve injury, pain, depression and anxiety.
Highlights

  • Whereas current anti-depressant and anti-anxiety medications take 1-2 months to take effect, and frequently produce very harsh side effects, 7,8-dihydroxyflavone is a potent anti-depressant that demonstrates therapeutic efficacy within a few days.
  • A similar compound, 5,7-dihydroxyflavone, has been approved for bodybuilding use in humans.
Technical Summary

The invention comprises flavone derivatives for the treatment of neurological disorders. These compounds are TrkB agonists, and mimic the action of the natural ligand, brain-derived neurotrophic factor (BDNF). TrkB is a receptor tyrosine kinase (RTK) with high affinity for neurotrophins, polypeptide growth factors responsible for neuronal differentiation and survival via signal transduction cascades. Decreased levels of the neurotrophin BDNF has been implicated in a number of neurological disorders. Administration of exogenous neurotrophins can stimulate nerve growth and survival, but is hampered by the poor drug-like qualities of the compound including instability, poor bioavailability, and low levels of brain penetration. Synthetic peptides, which mimic TrkB binding domains of BDNF, stimulate neuronal survival in vitro, but have not been shown to operate in animal models. In addition, large polypeptides with high molecular weights (ca. 2000) traditionally have proved difficult to develop with clinical success. The inventor has shown various flavonoids, the most active being 7,8-dihydroxyflavone, inhibit apoptosis in a number of cellular assays via a TrkB-dependent mechanism in T48 cells and primary hippocampal neurons. Strikingly, this compound exhibits potent neuroprotective effect against neuroexcitotoxicity and stroke in mice. It also reveals robust antidepressant effect in mice.
Developmental Stage & Potential Market
  • 7,8-dihydroxyflavone has been shown to be a potent anti-depressant in vivo and human clinical trials are being planned.
  • The compound and its derivatives have the potential to displace or augment a majority of the drugs in the $40 billion anti-depression and anti-anxiety market.

Source: http://emoryott.tech...technology/1860

#2 Reformed-Redan

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Posted 19 March 2012 - 06:29 PM

Question is, will 5,7 isomer do the same job? Since 7,8 is expensive.

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#3 Googoltarian

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Posted 19 March 2012 - 06:43 PM

Question is, will 5,7 isomer do the same job?

While it sounds similar, these two are different compounds, and therefore probably they have different actions.

Since 7,8 is expensive.

Source? Link?

Edited by Googoltarian, 19 March 2012 - 06:44 PM.


#4 Reformed-Redan

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Posted 19 March 2012 - 11:57 PM

Source? Link?

Lowest I could find:
http://www.sigmaaldr...ng=en&region=US

#5 OpaqueMind

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Posted 22 March 2012 - 01:20 PM

That looks fucking awesome!

Any idea what the effective dosage range is?

#6 Googoltarian

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Posted 22 March 2012 - 02:57 PM

Any idea what the effective dosage range is?


7,8-dihydroxyflavone, a small-molecule TrkB agonist, reverses memory deficits and BACE1 elevation in a mouse model of Alzheimer's disease.

Devi L, Ohno M.

Source

Center for Dementia Research, Nathan Kline Institute, Orangeburg, NY 10962, USA.

Abstract

Increasing evidence suggests that reductions in brain-derived neurotrophic factor (BDNF) and its receptor tyrosine receptor kinase B (TrkB) may have a role in the pathogenesis of Alzheimer's disease (AD). However, the efficacy and safety profile of BDNF therapy (eg, gene delivery) remains to be established toward clinical trials. Here, we evaluated the effects of 7,8-dihydroxyflavone (7,8-DHF), a recently identified small-molecule TrkB agonist that can pass the blood-brain barrier, in the 5XFAD transgenic mouse model of AD. 5XFAD mice at 12-15 months of age and non-transgenic littermate controls received systemic administration of 7,8-DHF (5 mg/kg, i.p.) once daily for 10 consecutive days. We found that 7,8-DHF rescued memory deficits of 5XFAD mice in the spontaneous alternation Y-maze task. 5XFAD mice showed impairments in the hippocampal BDNF-TrkB pathway, as evidenced by significant reductions in BDNF, TrkB receptors, and phosphorylated TrkB. 7,8-DHF restored deficient TrkB signaling in 5XFAD mice without affecting endogenous BDNF levels. Meanwhile, 5XFAD mice exhibited elevations in the β-secretase enzyme (BACE1) that initiates amyloid-β (Aβ) generation, as observed in sporadic AD. Interestingly, 7,8-DHF blocked BACE1 elevations and lowered levels of the β-secretase-cleaved C-terminal fragment of amyloid precursor protein (C99), Aβ40, and Aβ42 in 5XFAD mouse brains. Furthermore, BACE1 expression was decreased by 7,8-DHF in wild-type mice, suggesting that BDNF-TrkB signaling is also important for downregulating baseline levels of BACE1. Together, our findings indicate that TrkB activation with systemic 7,8-DHF can ameliorate AD-associated memory deficits, which may be, at least in part, attributable to reductions in BACE1 expression and β-amyloidogenesis.



#7 PWAIN

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Posted 23 March 2012 - 03:38 AM

So a 75Kg person would be:

5mg x 75Kg = 375mg x 10 days = 3750mg

So at $363.30 per 50mg Would cost 3750/50 x 363.30 = $27 247.50

Depressing.... :-D

Of course we are talking mice so that will mess things up even further.

#8 Reformed-Redan

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Posted 23 March 2012 - 10:54 PM

So a 75Kg person would be:

5mg x 75Kg = 375mg x 10 days = 3750mg

So at $363.30 per 50mg Would cost 3750/50 x 363.30 = $27 247.50

Depressing.... :-D

Of course we are talking mice so that will mess things up even further.

Anything new like this initially costs a lot.

#9 PWAIN

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Posted 26 March 2012 - 02:23 AM

Anything new like this initially costs a lot.


Yeah, research lab type stuff like this is always way up in price. Wonder what a Chinese lab would charge to make up a few grams. Anyone here keen enough to try?

#10 Reformed-Redan

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Posted 26 March 2012 - 03:59 AM

Yeah, you can count me in...

Though, I wounden't be too quick. Check here: http://www.scienceda...00125173459.htm

"It is likely that many people take in small amounts of 7,8-dihydroxyflavone in their diets," Ye says. "But drinking green tea or eating apples doesn't give you enough for a sustained effect."

In the initial screening process, several flavonoid compounds had similar properties to 7,8-dihydroxyflavone. Ye says his laboratory has already identified compounds that are several times more active.


In the meantime you can stock up on some resveratrol.

Edited by redan, 26 March 2012 - 04:08 AM.


#11 elovefire

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Posted 26 March 2012 - 10:57 PM

The Crysin ( 5,7-dihydroxyflavone) seems to be an anti estrogen for body builders, mostly steroid users.

So it doesn't seem good to take it for the effects of 7, 8-dihydroxyflavone.

Anyone know if I can get a prescription for 7, 8-dihydroxyflavone?? For department n anx ...

#12 Reformed-Redan

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Posted 27 March 2012 - 02:51 AM

It's not on the market yet. I read it may be of great use for those with PTSD.


http://www.scienceda...10112105149.htm

Living a traumatic experience favors the persistence of fear associated with an aversive stimulus, known as fear conditioning. Scientists in the US and Spain have now found that such effect, in mice, can be suppressed with a single dose of 7,8-Dihydroxyflavone, a type of flavonoid which boosts the ability to acquire new emotional behaviors...



#13 hullcrush

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Posted 27 March 2012 - 03:08 AM

It likely has a reduced oral bio-availability, and would be in dire need of a dosing study. It was injected in the rats.
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#14 Reformed-Redan

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Posted 27 March 2012 - 07:53 PM

Anyone know what this graph represents?
http://www.wipo.int/...44D390DE2.wapp1

#15 Reformed-Redan

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Posted 02 April 2012 - 05:17 AM

From:
http://www.neuro.cjb...22/8/3251.short

Previous studies demonstrated that antidepressant treatment increases the expression of brain-derived neurotrophic factor (BDNF) in rat hippocampus. The present study was conducted to test the hypothesis that BDNF in the hippocampus produces an antidepressant effect in behavioral models of depression, the learned helplessness (LH) and forced swim test (FST) paradigms. A single bilateral infusion of BDNF into the dentate gyrus of hippocampus produced an antidepressant effect in both the LH and FST that was comparable in magnitude with repeated systemic administration of a chemical antidepressant. These effects were observed as early as 3 d after a single infusion of BDNF and lasted for at least 10 d. Similar effects were observed with neurotrophin-3 (NT-3) but not nerve growth factor. Infusions of BDNF and NT-3 did not influence locomotor activity or passive avoidance. The results provide further support for the hypothesis that BDNF contributes to the therapeutic action of antidepressant treatment.

Christ.
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#16 Reformed-Redan

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Posted 05 April 2012 - 03:26 PM

To whom it may concern:
Oroxylin A has similar effects on the TrkB receptor as does 7 8-dihydroxyflavone. It can be found in the baicalensis group of skullcap. That's all folks. :)

Edited by redan, 05 April 2012 - 03:27 PM.


#17 Verne

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Posted 12 April 2012 - 06:45 AM

human clinical trials are being planned.


It's going to fail miserably. This always happens: Scientists/Chemists release promising results from early animal trials, media hype-storm ensues, lab gets funding approved, phase one human trials show promise, phase two humans trials draw some scepticism but don't rule out all hope, phase three trials fail miserably <insert disease> not cured. It wont work. I know it wont work. This sort of news crops up too often that false hope doesn't even start upon reading the headline anymore.
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#18 Reformed-Redan

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Posted 12 April 2012 - 01:57 PM

Hey it may be some dopamine rush that gives the illusionary effect that, "my life has taken a u turn... just let me redose". This stuff is really promising and deserves the optimism.

#19 Reformed-Redan

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Posted 17 April 2012 - 07:13 PM

Another way to help alleviate depression in a short amount of time:

http://www.sciencedi...361923009002020

Really helps. Feeling the effects.

Anybody who is in a major hole might want to consider cycling some nights off of sleep with intense exercise.

Edited by redan, 17 April 2012 - 07:15 PM.


#20 Junk Master

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Posted 18 April 2012 - 11:16 PM

Ever wonder if insomnia evolved to stimulate BDNF and alleviate minor depression?

#21 nupi

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Posted 21 April 2012 - 11:23 AM

Another way to help alleviate depression in a short amount of time:

http://www.sciencedi...361923009002020

Really helps. Feeling the effects.

Anybody who is in a major hole might want to consider cycling some nights off of sleep with intense exercise.


If lack of sleep was going against depression I would be one of the happier people around...
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#22 noos

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Posted 01 May 2012 - 05:24 AM

Pwain To calculate the dose you have To adjust for different metabolism so it is much lower.

#23 blighted

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Posted 26 May 2012 - 10:28 PM

There is a mention of human clinical trials being planned, but I can not find any information of safety, efficacy, or dosage in humans. Does anyone have references?

Seems like a BDNF mimetic that can be taken orally and cross the bbb is an holy grail in some respects.

I've ordered 1g and may try it out. As it's a flavone, it seems like it should be safe to ingest in reasonable quantities. However I would appreciate input from anyone who knows more.

#24 blighted

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Posted 26 May 2012 - 10:34 PM

I wish all scientific presentations were so well digestible. This to me indicates a major impact on plasticity:

http://psylab.idv.tw...al Learning.pdf

#25 blighted

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Posted 26 May 2012 - 10:41 PM

Question is, will 5,7 isomer do the same job? Since 7,8 is expensive.


"Compared with 7,8-dihydroxyflavone, 5,7-dihydroxyflavone (chrysin) had no prosurvival activity"

From:

http://www.pnas.org/...200913572SI.pdf


So the answer appears to be "no".

#26 nowayout

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Posted 27 May 2012 - 05:06 PM

Was looking around for strong NGF enchancers. Cam across something very promising:

Source: http://emoryott.tech...technology/1860


It looks like the text of a patent. Ignore it.

Patent applications are often hugely speculative, more often than not turning out to contain objectively false claims. There is no scientific standard of evidence for the truth of patent applications. They are just there to stake a claim of primacy, mostly before an actual serious scientific study is done, if it ever is.

Edited by viveutvivas, 27 May 2012 - 05:06 PM.


#27 golden1

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Posted 20 July 2012 - 08:34 PM

There are also studies, with the full texts on some of them available.. I wouldn't say ignore it at all..I'm not going to ignore piracetam because there was also a patent on it :P

Anyway I'm sure there is a chinese labout there who would make this for a FRACTION of the price of SIGMA, TORCRIS, and other professional US labs. I only know of a few.. and they specialize in RCs, but that might be a good thing since they may be more welcoming to a custom synth. However there is no way I could pay for a bulk amount of a custom synth alone... but I will ask some places.

#28 Reformed-Redan

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Posted 21 July 2012 - 05:37 AM

There are also studies, with the full texts on some of them available.. I wouldn't say ignore it at all..I'm not going to ignore piracetam because there was also a patent on it :P

Anyway I'm sure there is a chinese labout there who would make this for a FRACTION of the price of SIGMA, TORCRIS, and other professional US labs. I only know of a few.. and they specialize in RCs, but that might be a good thing since they may be more welcoming to a custom synth. However there is no way I could pay for a bulk amount of a custom synth alone... but I will ask some places.



Let me know on the minimum order size and cost. I'll also look at some prices.

#29 mycotheologist

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Posted 21 July 2012 - 04:39 PM

Mother of God, this is some find. Thanks a lot. Chemical suppliers in my country are pretty strict about not shipping to residential addresses, anyone have alternative routes for obtaining this?

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#30 Reformed-Redan

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Posted 21 July 2012 - 05:19 PM

I'm located in the US and am assuming that golden1 is. We would probably have some Chineese supplier on tradekey or alibaba synth it. Not sure if the supplier could send it to you or if we would have to from the group buy. I think 98% purity would be acceptable and not to hard on the wallet. The doses are very low, like 25mg?
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