25 replies to this topic

[world33]

I have watched a very interesting 2011 lecture on adult neurogenesis by Amelia Eisch, Associate Professor at UT Southwestern Medical Center
https://www.youtube....h?v=-jD5vl7xkuo

 

At 32:20 she mentions negative and positive factors in the adult neurogenesis equation:

 

Negative impact factors (less neurogenesis)

Stress
Age
Drug Abuse

 

Positive impact factors (more neurogenesis)

Enriched environment
Exercise
Hippocampal activity
Antidepressants

 

At 45:22 she also mentions Isoxazole-9 as a powerful compound that increases adult neurogenesis.

 

I searched this great forum for Isoxazole-9 and I was surprised to notice that there were just a few hits/comments about it and no specific dedicated thread.

 

My questions for the great longecity community are:

 

1) Why such a low interest in Isoxazole-9 considering this compound has been found out to be, for a few years now, as a powerful adult neurogenesis enhancer: http://www.ncbi.nlm....pubmed/22542682 ? Is it due to the fact that it is not easily available, expensive or because, as someone noticed, there are no official preliminary safety trials: https://clinicaltria...9&Search=Search
2) Can inflammation, alcohol or other factors be included in the Dr. Eisch's list of negative impact factors on neurogenesis?
3) What kind of Hippocampal activity exercises affect positively neurogenesis?
4) Would you consider a combo of NSI-189, Dihexa, 7,8 dihydroxyflavone, Isoxazole-9 and possibly cerebrolysin the holy grail of adult neurogenesis at this point in time?

 

Thanks for any feedback

Edited by world33, 01 June 2014 - 10:16 AM.

[Reformed-Redan]

Interesting, and more importantly seems feasible to make. Will see what THT has to say once they're up and running again at full capacity. Would absolutely love to try a combo of 7,8-DHF, NSI-189, and ISX-9, haha!

[ByAnyMeansNecessary]

Interesting, and more importantly seems feasible to make. Will see what THT has to say once they're up and running again at full capacity. Would absolutely love to try a combo of 7,8-DHF, NSI-189, and ISX-9, haha!

 

Indeed! THT.co, when they're back up WILL have NSI-189. It would be interesting to see if they'll carry ISX-9 (hopefully they will). 

 

Out of curiousity though, couldnt combining all three of them prove to be horrendously disastrous for the consumer? Or, would that risk be averted/not that high, given that they function on different mechanisms and portions of the brain? My concern is, it seems like a decent portion of adult neurogeneic drugs tend to have a cumulative effect. While initially they may not have that much of an impact, my concern is that down the road, the combination could end up being really terrible for you or possibly end up causing some sort of reversal of everything you've been trying to improve. 

 

 

My questions for the great longecity community are:

 

1) Why such a low interest in Isoxazole-9 considering this compound has been found out to be, for a few years now, as a powerful adult neurogenesis enhancer: http://www.ncbi.nlm....pubmed/22542682 ? Is it due to the fact that it is not easily available, expensive or because, as someone noticed, there are no official preliminary safety trials: https://clinicaltria...9&Search=Search
2) Can inflammation, alcohol or other factors be included in the Dr. Eisch's list of negative impact factors on neurogenesis?
3) What kind of Hippocampal activity exercises affect positively neurogenesis?
4) Would you consider a combo of NSI-189, Dihexa, 7,8 dihydroxyflavone, Isoxazole-9 and possibly cerebrolysin the holy grail of adult neurogenesis at this point in time?

 

 

In regards to question 2, I would say that yes, those factors are included in Dr. Eischs list of negative factors. Inflammation can be attributed to stress (as stress is both physical and psychological), and that alcohol is a drug (a lot of people seem to have a hard time accepting that it's a drug for some reason). 

 

As far as question 3, without really looking, I would imagine that working memory exercises would help increase this. The more you use a certain portion of the brain, the more its going to grow. 

Edited by ByAnyMeansNecessary, 01 June 2014 - 02:08 PM.

[Nattzor]

From what I know: 2 of them have been tested in humans (NSI and cere), two in animals (7,8 and dihexa) and one in nothing (not 100% sure though). This is risky as fuck.

 

As Jackass have told us a lot of times, do not try this at home.

[normalizing]

^ we need research chem jackasses series on youtube dosing on experimental stuff for us and broadcasting episodes on youtube. any takers?

[world33]

From what I know: 2 of them have been tested in humans (NSI and cere), two in animals (7,8 and dihexa) and one in nothing (not 100% sure though). This is risky as fuck.
 
As Jackass have told us a lot of times, do not try this at home.

Thanks for the info. Can this study on mice be considered like being tested on animals or there should be a proper specific safety trial?
http://www.ncbi.nlm....les/PMC3405259/

Do 7,8 and dihexa have safety trials on animals?

[Nattzor]

 

Thanks for the info. Can this study on mice be considered like being tested on animals or there should be a proper specific safety trial?
http://www.ncbi.nlm....les/PMC3405259/

Do 7,8 and dihexa have safety trials on animals?

 

 

Did not know that, sorry. So all tested in animals atleast.

 

7,8 does have safety trials afaik, can't link them at because I'm busy though. I might be wrong and it just has tons of studies, most showing protective effects (also protects from some forms of cancer).

[Milkyway]

If/when Isoxazole-9 does become available what does would we experiment with?

[world33]

If/when Isoxazole-9 does become available what does would we experiment with?

Adult neurogenesis as explained in this paper: http://www.ncbi.nlm....les/PMC3405259/

[drg]

isx-9 is being sold on teamtlr.com. Anyone try them out yet?

 

[medicineman]

isx-9 is being sold on teamtlr.com. Anyone try them out yet?
 

I made an order, isx-9 being one of the goodies I ordered. For personal reasons, I asked for my items to be held for me until I am able to collect them (logistics issue, which has nothing to do with teamtlr) but when I get it, I'll certainly give AbdulJabbar (my rat) a trial of it.

[Aurel]

 

 

4) Would you consider a combo of NSI-189, Dihexa, 7,8 dihydroxyflavone, Isoxazole-9 and possibly cerebrolysin the holy grail of adult neurogenesis at this point in time?

 

It would be great if someone with medical/biochemistry knowledge would have a look into this and explain to us on which pathways they work etc. Otherwise it could be very reduntant to take them all and so wasting some good money.

[Nattzor]

 

I made an order, isx-9 being one of the goodies I ordered. For personal reasons, I asked for my items to be held for me until I am able to collect them (logistics issue, which has nothing to do with teamtlr) but when I get it, I'll certainly give AbdulJabbar (my rat) a trial of it.

 

 

Even though I recommended against it (combining atleast), I've also fixed some.

 

 

 

It would be great if someone with medical/biochemistry knowledge would have a look into this and explain to us on which pathways they work etc. Otherwise it could be very reduntant to take them all and so wasting some good money.

 

 

NSI-189, mechanism unknown. It's neurogenic, synaptogenic (confirmed) and potentially it also does some stuff with neurotransmittors. Might only work in hippocampus, I doubt it a bit though.

Dihexa, based on Norleucine 1-angiotensin IV (which is related to vassopresin), highly synaptogenic, seems to work through the angiotensin AT4-receptor (because it's a stabilised, BBB-penetrating, orally active version of Norleucine 1-angiotensin IV). Probably more MoA I do not know off, every drug has. I'd guess dihexa might be insanly good for memory.

7,8-Dihydroxyflavone, TrkB agonist (same receptor BDNF, N-Acetylserotonin, NT-4, NT-3, and more activate). Synaptogenic, promotes plasticity, neurogenesis (maybe) seem to be the effects, also anti-cancer and some other).

Isoxazole-9, signals for stem cells to become neurons, not sure if only in the hippocampus. Mef2 seems invloved, changes gene expression a bit.

Cerebrolysin, neurotrophic (works as some endogenous neurotophic factors, afaik, it's not 100% known which peptides are involved).  Enhances neurogenesis, plasticity, decrease β-amyloid, reduce cell death, does tons of stuff. Read more here.

[Aurel]

Thank you Natt

[world33]

Can you guys provide this forum community with a bit of short and long term feedback when you receive and test Isoxazole-9 on yourself or your NBA mice?
medicineman I would be particularly interested in knowing whether Isoxazole-9 will give your AbdulJabbar mouse wings to an extent you would consider renaming it MichaelJordan. Thanks!

Edited by world33, 30 June 2014 - 03:37 AM.

[mamborambo]

GCaMP3 activation by Isoxazole-9

 

Organotypic hippocampus slice culture from a mouse with a floxed GCaMP allele with Cre expressed under a Nestin promoter. Isx-9 (20uM) was applied at the beginning of the video and the calcium fluorescent reporter was recorded for 10 minutes. This video plays at 40x original speed.

[Aurel]

Could you explain what happens in the video? It seems that the neurons beginn to fire. But would this be a good thing? I guess I dont want random neurons fire for no reason.

[jerey34]

yes i would consider that a bad thing also

[mamborambo]

GCaMP3 activation by Isoxazole-9

 

Organotypic hippocampus slice culture from a mouse with a floxed GCaMP allele with Cre expressed under a Nestin promoter. Isx-9 (20uM) was applied at the beginning of the video and the calcium fluorescent reporter was recorded for 10 minutes. This video plays at 40x original speed.

 

I found this video on youtube. I have to admit that I dont understand it. Hoped that the smarter people here on this forum could enlighten us.

[mamborambo]

does anybody know if there are plans for human trials with this?

[HappyShoe]

Anyone know the dosages in humans for this? Looking to order from teamtlr, and wish to know how much was used in animal studies and how to convert to human dosage.

[mamborambo]

Anyone know the dosages in humans for this? Looking to order from teamtlr, and wish to know how much was used in animal studies and how to convert to human dosage.

on their website it says this:

"ISX-9 dosing estimates as relates to any potential future human clinical trials, based off the animal data available, correlate to be anticipated at 75-150mg q.d. or b.i.d. for such focused toward neurogenic-dependent/neuroregenerative/anti-neurodegenerative (Alzheimer's Disease, et. al.) and antidepressant,/mood stabilizing treatments."

 

http://teamtlr.com/n...h/53-isx-9.html

Edited by mamborambo, 20 July 2014 - 04:51 PM.

[Amorphous]

Anyone receive and try it yet?

[telight]

Anyone receive and try it yet?

 

I received mine and took 15mg subliminally 10 minutes ago. So far no effects positive or negative. The powder has a high density and is light brown in color and coarse in texture. I will update my experience in the ISX-9 feedback thread as more time passes. http://www.longecity...-user-feedback/

Edited by telight, 25 July 2014 - 04:38 PM.

[sk_scientific]

I have received ISX-9 and will not begin dosing until the middle of next week.  In the interim, I am researching what little information there is on the compound and its peripheral actions, such as the induction of NeuroD1 expression.  I'm not disposed to the notion that enhanced NeuroD1 expression in the pacreas is necessarily desireable.  Be informed that ISX-9 purportedly manipulates an allele in your DNA.

 

We haven't established what a safe amount, and perhaps more especially, what a safe duration of doseage is for this substance.  Until I know more, I am inclined to tread very lightly.  I will appreciate any user experiences in the feedback thread.  It would be very beneficial for us to have an individual who is not needle adverse to monitor their blood sugar.  I'm extremely needle adverse so in this go-round I'm going to have to hand that torch to another (unless of course we do find that this substance does dramatically effect insulin levels and in such case it would become a necessity that anyone ingesting it monitor their blood sugar levels).

 

Please update in the  ISX-9 feedback thread.

Edited by sk_scientific, 06 August 2014 - 02:12 PM.

[sk_scientific]

 

Anyone receive and try it yet?

 

I received mine and took 15mg subliminally 10 minutes ago. So far no effects positive or negative. The powder has a high density and is light brown in color and coarse in texture. I will update my experience in the ISX-9 feedback thread as more time passes. http://www.longecity...-user-feedback/

 

 

After subliminally receiving it, do try it under your tongue. ;-)