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7,8 dihydroxyflavone (group buy)

neurogenesis antidepressant

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#301 world33

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Posted 16 June 2014 - 11:12 PM

7,8 dhf is meant to increase adult hippocampal neurogenesis which takes several weeks. You still might feel short-term positive effects but it is not meant to be a as an aspirin for headache. I would also take 50mg in the morning and 50mg at night (recommended dosage 5mg per Kg of your weight; for example if you weight 75kg the recommended daily dosage is 375mg). If still you do not experience any benefit you might consider to switch to NSI-189 which is similar in the adult hippocampal neurogenesis goal.

 
Source? Afaik, 7,8 have not been tested in humans and have no recommended dose for humans. Is the 5 mg / kg from a rat/mouse study? Have you converted it?
 
When I converted the dose I got around 10 mg per 25 kg iirc.


Just followed PWAIN post at http://www.longecity...3-4-days-study/
and socialpiranha maximum dosage at http://www.longecity...hydroxyflavone/

They might be wrong and your conversion mouse->human more appropriate.

#302 Milkyway

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Posted 17 June 2014 - 01:42 AM

Has anyone been able to confirm or discredit the legitimacy of the 7,8 dihydroxyflavone from THT?  Was it ever tested or did anyone take it and also try some from another vendor and notice any difference.  I am trying to decide whether to try it again after going through a gram of THT'S.



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#303 Flex

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Posted 17 June 2014 - 01:54 AM

Aphex has have ordered it.

As far as I remeber, he talked about it in another dhf thread


Edited by Flex, 17 June 2014 - 01:55 AM.

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#304 Nattzor

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Posted 17 June 2014 - 10:25 AM

 

Just followed PWAIN post at http://www.longecity...3-4-days-study/
and socialpiranha maximum dosage at http://www.longecity...hydroxyflavone/

They might be wrong and your conversion mouse->human more appropriate.

 

 

PWAIN is incorrect (you need to convert the dosage), I sadly don't see where socialpiranha talks about dosages except for what doses he tried. (He is also wrong that it raises BDNF, it's "just" a TrkB agonist, although I just think he worded it poorly.)

 

From mouse to human dosage: 5mg/kg * (3/37) = 0.4054054054mg/kg

 

0.4054054054mg/kg * 75 kg= 30.4054054054 mg

 

So about 10 mg per 25 kg. This is just one study (and they used IP injections, gives a bit better bioavailability afaik), so check other studies for other dosages.

 

http://www.ergo-log....umandosage.html - How to calculate



#305 world33

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Posted 17 June 2014 - 10:53 AM

Thanks for that. So if it is 10mg per 25Kg with injections could we safely say that orally it should be higher?
Btw I tried 50mg in the morning and 50mg in the evening with no side effect, but considering your advice I will reduce to 50mg daily

Edited by world33, 17 June 2014 - 10:55 AM.


#306 blood

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Posted 17 June 2014 - 11:04 AM

5 mg/ kg was the dose for mice used in several papers (potent antidepressant effects, etc were seen at that dose).

Edited by blood, 17 June 2014 - 11:05 AM.


#307 Nattzor

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Posted 17 June 2014 - 11:41 AM

Thanks for that. So if it is 10mg per 25Kg with injections could we safely say that orally it should be higher?
Btw I tried 50mg in the morning and 50mg in the evening with no side effect, but considering your advice I will reduce to 50mg daily

 

IP injections = Intraperitoneal injection. So not IM, IV or SubQ, but rather between the organs if I understand it correctly.

 

5 mg/ kg was the dose for mice used in several papers (potent antidepressant effects, etc were seen at that dose).

 

Also oral doses?



#308 aphex

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Posted 17 June 2014 - 03:01 PM

I have been taking 30mg daily from tht.co for 9 days now.

The first few days I took it orally and the sublingually.

 

I have no other product to compare, but I consider buying from Indofine which also supplied a DHF studiy like I've read here.

 

I think that I notice some effects but I cannot be sure that they are not placebo.

An immediate effect I get after 30mg sublingually in the evening (tired and stressed sometimes) is that I get a more relaxed and also more wakeful body feeling and mind. I meditated regularly for months until about these 9 days ago. The day I took 7,8-DHF and meditated it was easier for me to reach the relaxed meditation state I usually recognise by its closed-eye-visuals. I also think that it amplifies the antidepressive effect I get from prescribed venlafaxine.

I cannot measure my blood pressure but I think pulse and BP go down when I take it. After taking it I sometimes have the that my heart "stumbles".

 

Back to bioavailability:

This site states that 7,8-DHF among other dihydroxyflavones has very poor oral bioavailability due to glucoronidation in the liver (first-pass-effect):

http://www.researchg...hydroxyflavones

Another studiy that investigates a derivative compound state that it is orally bioavailable but does not say something about the extent:

http://www.ncbi.nlm....pubmed/21073191

Also keep in mind that it was only tested in animals (rats or mice) and was applied IP or IV but surely not orally in the other studies.

I would conclude that it is bioavailable but not very much. Same with Chrysin (5,7-DHF).

 

I cannot find something about it's sublingual bioavailability. Someone mentioned in a forum that it would be better to take Chrysin sublingually than orally.

 

If you take something sublingual it will bypass the first pass effect. I have read that it's especially useful for fast acting lipophilic substances.

 

I don't know something about the lipophilicity or other chemical properties of 7,8-DHF.

Is there someone - maybe with pharamcological or chemical background - that can elaborate that?

I just can find that it "Soluble in ethanol to 25 mM and in DMSO to 100 mM":

http://www.abcam.com...f-ab120996.html

I think it won't help to take it with methonal for example because methonal damages your buccal mucosa.

I won't consider to inject something and surely not this research chemical that isn't surely pure but I would smoke it with a vaporzing DMT/meth pipe. :D

It would also have to be lipophilic for that. The molecule size also matters then. The smaller the better I think.

 

I also noticed that the powder stays very long under my tongue, about 40 to 60 minutes. How long should I keep it there? Maybe only the byproducts stay there and the 7,8-DHF dissolves? I get the (placebo) effect before I cannot see the powder under my tongue anymore.

I can try to press my tongue between my teeth to 'seal' the region under my tongue. Otherwise I've read that the salivation could wash it away.

 

Any adwises on how to take it?


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#309 formergenius

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Posted 17 June 2014 - 04:10 PM

Hmm good points there.. I don't suppose anyone has tried it intranasally yet? I vaguely remember reading an account of such where 150mg was insufflated.

But if it is first-pass inhibiting bioavailability, then indeed sublingual administration should prevent that, depending on the sublingual absorption rate of course (Something I alas can't properly address. Indeed dissolving it might enhance solubility.. Why the comment on methanol when one can use ethanol?).

 

Considering that THT's 7,8-DHF's purity has been questioned, I wouldn't go about injecting it either. But if one was certain it was significantly pure, perhaps tyndallization to sterilize the material and dissolving it in an injectable medium would be an option to make it injectable, though you would have to know its thermolability I suppose. I'm no chemist.

I don't see why injecting such a research chemical would be any less advisable than other RoA's unless you're speaking of IV, in which case I would avoid that too. But other than that.. I'd rather have it end up in a muscle/fat than in my lungs, should it turn out to have ill effects.. Just saying.

Alternatively, and understandably unattractive, rectal? *shiver*


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#310 Flex

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Posted 18 June 2014 - 11:54 AM

Considering that THT's 7,8-DHF's purity has been questioned, I wouldn't go about injecting it either. But if one was certain it was significantly pure, perhaps tyndallization to sterilize the material and dissolving it in an injectable medium would be an option to make it injectable, though you would have to know its thermolability I suppose. I'm no chemist.

I don't see why injecting such a research chemical would be any less advisable than other RoA's unless you're speaking of IV, in which case I would avoid that too. But other than that.. I'd rather have it end up in a muscle/fat than in my lungs, should it turn out to have ill effects.. Just saying.

Alternatively, and understandably unattractive, rectal? *shiver*

 

- Hmm, Wouldnt there be some undissolved particles left ?

could they still clogging arteries etc even with IM injection?

 

Honestly, just asking.

 

- LoL rectal. This reminds me of the bluelight forum and psychonaut forums.

This was relative common.

It is effective, but I´d rather avoid it as well

 

Doing a research chemical IV wasnt even for some a big problem O.O


Edited by Flex, 18 June 2014 - 11:54 AM.


#311 penisbreath

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Posted 18 June 2014 - 02:39 PM

It's kind of been hard to gauge if people are seeing much effect from the 7,8-dihydrox at all .. socialpiranha described it as an SSRI-minus-the-sfx, which sounds promising, but then others are making more vague/uncertain references to being less overstimulated etc., without much mention of cognition

 

the thing that interested me most was a) its supposed ability to positively influence sensory-gating deficits, and b) related to (a).. its supposed influence on schizophrenic-like cognitive deficits.

 

is the problem that people are already taking it with ADs? or simply don't have rather profound cognitive issues? 



#312 aphex

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Posted 18 June 2014 - 04:56 PM

Depression and cognitive issues caused by depression go hand in hand I think. The most prominent effect for me was the antidepressive one, but that of course led to cognitive enhancement.

I can't say whether it also would help healthy individuals for cognitive enhancement.

This sum-up-article of wikipedia explains the importance of BDNF (agonizes TrkB receptor like 7,8-DHF) and neuroplasticity which is greatly modulated by BDNF or TrkB in the human brain:

https://en.wikipedia...roscience_basis

NGF e.g. binds to TrkA and is more resposible for sensory, motor and sympathic functions IIRC.

BDNF, hippocampus atrophy (hypotrophy) and neuroplasticity are keywords for depression and cognitive enhancement as well.

For example I've read somewhere that the hippocampus volume correlates with cognitive funtions, the IQ etc. You know that hippocampus hypotrophy is not only responsible for cognitive matters but also for depression, mood, stress response and so on.

The hippocampus is also the most important place where neurogenesis takes place while BDNF's action (neurogenesis but also neuroplasticity and neuroprotection) is distributed over the whole CNS.

 

I don't know whether it could help with schizophrenia or sensory gating deficits like HPPD. HPPD isn't well researched but research suggests a link between HPPD and PTSD. PTSD can also be treated with hippocampal neurogenesis (see NSI-189) and is linked to stress. Hippocampal neurogensis helps coping with stress while more stress on the other side ampflifies psychosis (schizophrenia) and HPPD like many people report.

Though I haven't googled a possible correlation of neurogenesis/hippocampus ans psychosis.

 

Sorry.. I'm constantly in a hurry since some days or weeks and don't have the time to proof what I write with e.g. PubMed but I'm sure the most isn't speculation it's actually based on the bunch of information I've read over the time like everyone else here I guess.

 

Very long story short: I also think that unfortunately mainly people with mood disorders (anxiety, depression...) tried DHF and reported here.

It seems that the quality of the DHF products around like from tht.co and the bioavailability matters more than the mechanism of action. One can compare the effects with NSI-189, Dihexa and other neurogenics that act via the neurotrophic pathways.

 

Btw, I just snorted my 30mg evening DHF dose. At least it doesn't reach my throat and doesn't hurt. It's annoying to keep it one hour under my tongue every evening...

I think that I feel the relaxing effect again. I believe that there is an acute onset/effect. Caffeine and aerobic exercise also have acute nootropic effects via BDNF...

Can someone compare the bioavailability of sublingual vs. intranasal administration?

I think the difference is just the absorption area but it should also be suited to bypass the liver and for lipophilic substances right? (Still don't know whether DHF is actually lipophilic.)

If there is the scientific basis and proof of safety/purity then I would try other routes of administration but at the moment I don't know enough about all that...

 

One should have the 7,8-DHF derivative:

http://www.ncbi.nlm....les/PMC3150605/

"4'-Dimethylamino-7,8-dihydroxyflavone displays more potent stimulatory effect on TrkB receptor than the lead"

Couldnt find something about bioavailability in there so far...


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#313 penisbreath

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Posted 19 June 2014 - 04:38 AM

Gotcha. When you wrote "I think that I notice some effects but I cannot be sure that they are not placebo," I assumed the benefits were very slight/non-apparent.

 

I'm not so much concerned with brain enhancement in "healthy individuals", since I'm far from healthy. I don't have HPPD or schizophrenia -- but OCD, ADD, PTSD .. tardive akathisia .. and schizophrenia-like deficits, i.e. loss of mental visualization, thought/idea poverty, difficulty filtering out noise, very easily overwhelmed by excessive visual information etc. My subjective state is one of intense inner disorganization.

 

Here's one study on schizophrenia:

 

"

Small-molecule TrkB agonist 7,8-dihydroxyflavone reverses cognitive and synaptic plasticity deficits in a rat model of schizophrenia."

 

and on sensory gating

 

Effects of TrkB agonist 7,8-dihydroxyflavone on sensory gating deficits in mice after administration of methamphetamine.

 

I'm very eager to try the tht.co stuff and am eagerly awaiting them opening their doors again. Of course, who knows what it might do... and like you say, purity is probably an issue. Since my issues are rather profound, and I don't take any other medication, I'm hoping there might be some benefits. I expect it probably wouldn't be very helpful for ADD/processing speed/sustained attention etc. though the dopamine regulation sounds like it might make other stimulants more tolerable. 

 

 



#314 Flex

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Posted 20 June 2014 - 01:10 AM

If someone is interrested:

 

Infralimbic BDNF/TrkB enhancement of GluN2B currents facilitates extinction of a cocaine-conditioned place preference.

....Our results show that this signaling cascade bidirectionally regulates extinction of a cocaine-induced conditioned place preference (CPP), a task that requires behavioral flexibility. Blockade of infralimbic TrkB receptors or GluN2B-containing NMDARs disrupted consolidation of extinction of the CPP. In contrast, extinction was strengthened by potentiation of TrkB receptor activity with infralimbic infusions of BDNF or systemic injections of 7,8 dihydroxyflavone (7,8DHF), the newly synthesized TrkB receptor agonist. The 7,8DHF-induced enhancement of extinction was prevented by infralimbic infusions of a GluN2B-specific receptor antagonist, demonstrating that TrkB receptor activation enhances extinction of cocaine-CPP via GluN2B-containing NMDARs. Together, infralimbic TrkB receptor activation strengthens GluN2B-containing NMDAR currents to support extinction learning....

http://www.ncbi.nlm....pubmed/24760865


Edited by Flex, 20 June 2014 - 01:11 AM.


#315 aphex

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Posted 21 June 2014 - 09:13 PM

I just have to report some changes again:

 

Since I have been snorting 30mg tht.co DHF in the evening for 4 days now I am experiencing HUGE overall improvements!

It's been two weeks now since I have taken it the very first time, first orally, then sublingually and now intranasally; always 30mg.

 

First I experienced subtle effects I couldn't surely distinguish from placebo like already posted before: relaxation, increased more stable mood. When I took it sublingually the onset of action was quicker.

After a few days of snorting it I experience these effects:

  • Drastically heightened and very stable mood. Almost no remaining signs of stress and aggression I lately had trouble with.
  • I'm much more self-confident and offensive. There is not much that frustrates me, I am constantly learning and working on everything. It's like a special form of motivation.
    That led to productivity I rarely experienced before in my life. I am using much more time of the day and got things done now I dreamed of years before.
  • I am much quicker in understanding and learning. It's very easy now to leave old habits (social anxiety, obsessions/compulsions) behind and replace them with much more efficient ones. I think I am even more eloquent. I am not a native english speaker but it gets easier to learn english in every day use (programming at work, writing here, researching there etc.).
  • I cannot say much about memory, at least not short-term-memory. I think it isn't changed. But my episodic memory of facts and experiences (long-term-memory) seems greatly improved looking days in the past.
  • The absolutely most obvious and prominent effect for me is the increase of visual acuity, especially in terms of spatial recognition and memory. It is very similar to the enhanced perception I experienced with lion's mane (TrkA (NGF) not TrkB (BDNF) enhancer) before. It is that strong that I can tell for sure that I experience concrete effects that aren't placebo.
  • I have no methylphenidate-induced rebound I had 3 times (due to 3 doses) before for nearly a year. My daily living evolved to continious flow of action and emotion. I am not in zombie mode like you may be on stimulants.

All that went to the extent that I questioned whether I am maniac now, e.g. like I was about a year before due to excessive modafinil usage. I am sure that I am not because my drive, mood etc. is not by far that effusive.

I still wonder how far that can go, a few months ago I was depressive and now I am in constant transhumanist cheater godmode tackling everything around me. It is by far the most solid effect I get from any drug or nootropic and I've done many and different ones for a long time before!

The effects are very similar to what you can read in the NSI-189 thread. It is pretty much what I expected with my research on neurogenesis, neuroplasticity and hippocampal volume and what I would expect from NSI.

 

Something about my regimen and condition if that matters:

I also meditate some days in a week and do intense aerobic exercise every 2 - 3 time a week (60 min. running or 45 min. swimming).

My current daily regimen without the DHF is:

  • 3 g fish oil (alternative ADHD treatment, focus, depression)
  • 2 g gotu kola (overall mental health, focus, memory, stress)
  • 2,400 mg N-acetylcysteine (OCD, impulsivity)
  • 5mg melatonin (delayed-sleep-phase-syndrome probably due to ADHD/OCD)
  • 60mg methylphenidate (ADHD, prescribed)
  • 75mg venlafaxine (social phobia, occasional depression, OCD, prescribed)
  • curcuma (curcumin) w/ black pepper (piperidin) (few powdered grams from the supermarket each) (stress, depression, neurogenesis, allergic rhinitis)
  • B-complex (prophylactic)
  • Magnesium citrate (prophylactic for aerobic exercise & ADHD, reduces MPH tolerance via NMDA, stress)
  • (55 mcg fluticason fuorat (glucocorticoid, allergic rhinitis, prescribed))

I have been taking these drug for a pretty while now (several weeks to months to nearly a year) and it's just the DHF I added lately so I think I can relate effects I notice.

You may think that these drugs are quite a lot but I have selected them very carefully with much scientific research (PubMed) and even my doctor approves their usefullness. It's not that (for some useless) eclectic collection of racetams, choline sources and vitamin C you can read about here often...

 

 

Though I still would prefer NSI-189 because is it much better researched. The nootropic effect of DHF even makes me more careful I think.

There still could be some bad adverse effects and I've read on PubMed that NGF and BDNF can support the growth of tumors. Does somebody has data or theory on neurogenesis-induced (brain?) tumors?

--> The whole thing is too good to be true :D :/ ...


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#316 Jbac

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Posted 22 June 2014 - 12:03 AM

So intranasal works better than sublingual?

#317 aphex

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Posted 22 June 2014 - 08:48 AM

So intranasal works better than sublingual?

I'm sure it works better, but I have no data for that, it's just my subjective experience.
I've found it annoying to keep it so long under my tongue. Absorption seems better intranasally.
Maybe a nasal spray would be good :D

#318 Amorphous

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Posted 24 June 2014 - 07:33 PM

Is there any good source to get 7.8 DHF other than tht.co and indofine?

#319 Nattzor

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Posted 24 June 2014 - 08:53 PM

Is there any good source to get 7.8 DHF other than tht.co and indofine?

 

There's a new player in town, http://teamtlr.com/n...flavone-99.html

They got some deal where you get 20% more than you ordered and some free HCBT-OX (herbal extract that is suppose to be neurogenic). You'll get 1g of herbal if you order 2g 7,8-DHF and 2 g if you order 5g.


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#320 Ezeon

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Posted 24 June 2014 - 09:46 PM

I'm considering purchasing 7,8-DHF and NSI-189 from 'mentioned vendor'. Anyone has any experience with this vendor and the quality of their products?


Edited by Ezeon, 24 June 2014 - 10:00 PM.


#321 Nattzor

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Posted 24 June 2014 - 10:01 PM

They just started, so no one has experience with them afaik. The 7,8-DHF is for pre-order, so they don't have it yet.

 

You should be able to get CoA on the NSI-189 they currently got if you send them a mail. Might give some trust.



#322 PWAIN

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Posted 24 June 2014 - 10:17 PM

Nattzor and others. When someone sends a private message with a vendor that obviously wants to keep a low profile, please don't post the name or details in the forums.
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#323 Ezeon

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Posted 24 June 2014 - 10:19 PM

I agree. Some trust is needed based on the few suppliers available for some compounds. The price seems reasonable, so I might give it a try.


Edited by Ezeon, 24 June 2014 - 10:19 PM.

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#324 Nattzor

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Posted 24 June 2014 - 10:21 PM

Nattzor and others. When someone sends a private message with a vendor that obviously wants to keep a low profile, please don't post the name or details in the forums.

 

Or they've talked to me and said I could post.


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#325 Amorphous

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Posted 24 June 2014 - 11:29 PM


Is there any good source to get 7.8 DHF other than tht.co and indofine?

 
There's a new player in town, http://teamtlr.com/n...flavone-99.html
They got some deal where you get 20% more than you ordered and some free HCBT-OX (herbal extract that is suppose to be neurogenic). You'll get 1g of herbal if you order 2g 7,8-DHF and 2 g if you order 5g.

Thanks. I visit the site before but had'nt noticed it has 7,8 DHA
I guess there will be only 1 g extra if I order the 5g package because of the 20% overfill for pre-order. Did I overlook some where for the 2 g extra for the 5 g order?

#326 Nattzor

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Posted 25 June 2014 - 07:28 AM

 

 

Is there any good source to get 7.8 DHF other than tht.co and indofine?

 
There's a new player in town, http://teamtlr.com/n...flavone-99.html
They got some deal where you get 20% more than you ordered and some free HCBT-OX (herbal extract that is suppose to be neurogenic). You'll get 1g of herbal if you order 2g 7,8-DHF and 2 g if you order 5g.

Thanks. I visit the site before but had'nt noticed it has 7,8 DHA
I guess there will be only 1 g extra if I order the 5g package because of the 20% overfill for pre-order. Did I overlook some where for the 2 g extra for the 5 g order?

 

 

Sorry for not being clear, but I was talking about the HCBT-OX. So if you order 5g, you'll get 6 g of 7,8-DHF and 2 g of HCBT-OX.



#327 Al Capacino

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Posted 25 June 2014 - 05:20 PM

Nsi189 phosphate and base.
Can anyone tell me the difference in these 2 products they have?

#328 Al Capacino

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Posted 25 June 2014 - 07:23 PM

actually ignore my last question I have found out on another thread.



#329 lourdaud

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Posted 26 June 2014 - 10:07 AM

sample arrived today just trying to find a good cheap place to have it tested last place fell through.

 

Any news?



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#330 penisbreath

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Posted 30 June 2014 - 02:58 PM

This is interesting:

 


TrkB partial agonists: potential treatment strategy for epilepsy, mania, and autism.
Abstract

Brain-derived neurotrophic factor (BDNF) is a member of a family of neurotrophins that, by activating a tyrosine kinase B receptor (TrkB), regulates a wide variety of processes in the nervous system, including neural development, function and survival. Evidence suggests that excess BDNF is involved in the pathogenesis of epilepsy, mania and autism. Thus, agents that can decrease BDNF-TrkB pathway signaling may be therapeutic for these diseases. However, blocking BDNF-TrkB pathways with TrkB antagonists may be harmful, as BDNF-TrkB deficiency has been related to major depression and Alzheimer's disease. A partial agonist is an agent that elicits a maximum response that is less than that of an agonist (e.g., the physiological ligand), so, in the presence of excess full agonist, a partial agonist would act as an antagonist. Interestingly, a dopaminergic partial agonist, aripiprazole, has been successfully developed for the treatment of psychotic disorders. Recently specific TrkB partial agonists have been synthesized by O'Leary and Hughes; it is proposed that these partial TrkB agonists may provide a novel strategy for the treatment of epilepsy, mania or autism, which may be associated with BDNF-TrkB hyperfunction.

 


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