1569 replies to this topic

[Strangelove]

Nice, always impressed on what is going on, in longecity!

[sk_scientific]

doesn't Dihexa need to be IVed? or I'm I thinking of GLYX 13

Not surprisingly because of its stability, hydrophobic character, and small size, dihexa was predicted to be orally bioavailable. The predicted effective human jejunal permeability (Peff) value represents the predicted effective human jejunal permeability of the molecule (Table 4). The predicted Peff value for dihexa (1.78) is intermediate between the predicted Peff values for enalapril (1.25) and piroxicam (2.14), two orally bioavailable drugs. Dihexa was also predicted to be 22.59% unbound to plasma proteins in circulation, thus making it available for distribution into the tissues.

http://www.ncbi.nlm....les/PMC3533412/

I would really appreciate some group effort in evaluating this article.

I will say that I contacted an individual involved in CURRENT Dihexa research who stated, "We are preparing a rather complete paper on Dihexa that will appear in the Journal of Pharmacological and Experimental Therapeutics in a few months. Until then I am not free to discuss Dihexa with the many people who have contacted me."

Some other individuals have been more helpful, though I can not particularly fault the person mentioned above; Perhaps he's protecting his brand?

Edited by sk_scientific, 19 February 2014 - 11:51 PM.

[sk_scientific]

Uninteresting, the lack of movement on this topic.

[xks201]

Uninteresting, the lack of movement on this topic.

What exactly are you referring to? I want to get a dose agreed upon so I can get a quote.

As of today 4 members here not including me emailed me to be in the group buy.

Remember we need enough people to even consider getting this produced...I am going to start a new thread in this subform just announcing the group buy is underway.

Edited by xks201, 20 February 2014 - 02:12 AM.

[sk_scientific]

Uninteresting, the lack of movement on this topic.

What exactly are you referring to? I want to get a dose agreed upon so I can get a quote.

As of today 4 members here not including me emailed me to be in the group buy.

Remember we need enough people to even consider getting this produced...I am going to start a new thread in this subform just announcing the group buy is underway.

I have a lot that I would like to say to you at the present, but before I "jump the gun" I would request that you respond to my email with the information that I have requested as I have made good there, with you, already.

In addition, I believe that a quick, informal, preliminary fact-finding on prices in terms of grams, hectograms and kilograms would look good on you.

I'm biting my tongue, please understand.However, I would also like to mention that that you assumed a position of leadership on your own accord. As such you have agreed to holding yourself to a slightly higher standard of integrity than the typical citizen.

Get your ass in order, please, sir.

[socialpiranha]

What is the current research status of dihexa, is it in clinical trials now? When was the phase 1 study done?

[sk_scientific]

It looks like the rats in the study I linked to earlier:

http://www.ncbi.nlm....les/PMC3533412/

Were fed 1.2 to 2 mg/kg of Dihexa orally per day.

I still haven't figured out the HED based on BSA conversion yet.

I'm reaching out to ScienceGuy to see if I can get his assistance.

Edited by sk_scientific, 20 February 2014 - 10:31 PM.

[sk_scientific]

Thanks very much to ScienceGuy for pointing me in the right direction. Here it is, prospective therapeutic dose based on animal to HED.

HED (mg/kg) = Animal Dose (mg/kg) x [Animal Km / Human Km]

Human Km = 37

Mouse Km = 3

Rat Km = 6
=============


2mg x [6/37] = 0.324 mg/kg

150 lb male = 68.03 kg

22.05mg, QD for a 150 lb male

Edited by sk_scientific, 21 February 2014 - 07:23 AM.

[jabowery]

Please cross check that with Xenix's HED calculation:

http://www.longecity...a/page__st__360

Thanks very much to ScienceGuy for pointing me in the right direction. Here it is, prospective therapeutic dose based on animal to HED.

HED (mg/kg) = Animal Dose (mg/kg) x [Animal Km / Human Km]

Human Km = 37

Mouse Km = 3

Rat Km = 6
=============


2mg x [6/37] = 0.324 mg/kg

150 lb male = 68.03 kg

22.05mg, QD for a 150 lb male

[celebes]

Please cross check that with Xenix's HED calculation:

http://www.longecity...a/page__st__360

Xenix arrived at the MG per KG dose, which would have to be multiplied by bodyweight.

[sk_scientific]

Xenix made a mistake. He made some weird calculations and then he second guessed himself regarding multiplying to come to determination of HED based on his own weight. The formula clearly calls for:

HED (mg/kg) = Animal Dose (mg/kg) x [Animal Km / Human Km]


This really is quite a simple formula. You can do the math that I provided.
HED in milligram per kilogram equals = animal dose in milligram to kilogram times [Animal KM divided by Human KM]

So you do the part in brackets first, then you multiply the animal dose and arrive at HED in milligram dose to kilogram weight.

HED = 2mg x [6 / 37]

HED = 2mg x .162162162

HED = .324324324 mg/kg

Finally you take that HED value and multiply it by your weight in kilograms.

150lb = 68kg

68 x .324324324 = 22.054054054 mg for 150 lb male

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

So in the end, and I don't want to confuse anyone. HED is in milligram dose to kilogram weight. Dose must be calculated based upon your weight once you have determined the HED.

Edited by sk_scientific, 21 February 2014 - 06:00 PM.

[sk_scientific]

One more thing that I should mention is that the expression 2mg/kg isn't a mathematical expression like: 2[y/5].

2mg/kg means 2 milligrams of dose per kilogram of body weight.

Edited by sk_scientific, 21 February 2014 - 06:11 PM.

[Jeoshua]

Did you really need to explain that part? I think we all know mg/kg measures, even if some of us don't know our weight in kilograms.

And as long as we're being uber technical, the dosage you arrived at is 324 mcg/kg

[sk_scientific]

I mentioned this mg/kg because it appears that Xenix had some confusion on the matter, which is what Jabowery was referencing. .324 mg is the same thing as 324 mcg. I felt it was better to leave it in mg to alleviate any confusion in the math for folks who might be grappling with it.

Additionally, I followed up with a professional Toxicologist on my estimate and this is what they had to say:

Hi Sk_Scientific,

I agree with your math. Keep in mind, though, this is really an over-simplified way of just finding a dose to start with. Also you would normally have data in multiple species to get an idea about inter-species differences and you would base your human dose on your most sensitive species. Additionally, you would probably add at least a 10x safety factor for your starting dose. Then, depending on pharmacokinetic and pharmacodynamic differences between humans and the other species, your ‘true’ human dose could ultimately end up quite different.

[sk_scientific]

Sigh. Come on guys. A little less social loafing and a little more group effort would go a long way to success.

[xks201]

I will be sending out for quotes Monday. Thank you to SK_Scientific for verifying the chemical structure. Last week SK_Scientific did most of the work. Next week my work/school schedule is less and Monday I am planning on devoting several hours or more to obtaining quotes to see realistically what the buy in prices would be. Thank you to everyone for your patience and please thank SK_Scientific for his work here thus far. I hope none of you confuse his enthusiasm for impatience...as well all know impatience is often a good thing.

As of right now I expect the group to do nothing unless they are in contact with Xenix or other users that claimed to have purchased Dihexa. In that event I would be curious who they received it from and for how much (it may have been bad dihexa if it was based on a chemical structure found online). If you would like to recommend a supplier you can also do that via the yahoo forum or here.

Edited by xks201, 23 February 2014 - 12:55 AM.

[sk_scientific]

I really, very much do appreciate the post, xks201 and you are correct in your assessment of my enthusiasm -- I am hopeful for this substance, and am looking forward to our successful procurement. Where you and I are assuming certain roles in this adventure, I recognize that a diversity of talent will contribute to the best possible outcome given a veritable lack of concrete information on Dihexa. To put it another way, there are a number of brilliant minds around this site, and I feel that if I could manage to somehow motivate their contribution, I believe that we all potentially stand to profit (not monetarily, but intellectually, experientially, or cognitively). I accept that members of the traditional academic institution will discourage some actions and methods present in our endeavor but that, whatever the outcome, society is likely to gain something from what we're up to, be the outcome positive or negative respective of our decisions.

Where I have my own very selfish reasons to be present in this arrangement, I strongly believe that if our risks bear a positive outcome, we may do humanity a brave service to have taken these risks. The collaborative effort on this substance is distinguishable from a number of other activities of far less noble intent, and in my opinion, this is a good cause for health and humanity; Mine, yours and everybody's.

So, I'll assist further where I can and I am thankful for your commitment in the coming weeks.

Edited by sk_scientific, 23 February 2014 - 07:37 AM.

[xks201]

I just want to say guys - I think SK and I have discovered why the last 2 users of Dihexa (and only 2 users known to us) did not see results. We believe they may have been using a chemical structure which was inaccurate and posted by some academic online.

We may need more users to get this buy going. We are still getting quotes. This BDNF ligand is potentially the greatest nootropic in existence. It appears that not only is it upregulating nerve growth factors but it is acting as a ligand to the receptors if I am interpreting the studies correctly. I personally know that many diseases begin in the nervous system. We see antidepressants working not primarily for their serotonin increasing potential but for their upregulation of nerve growth factors.

We do not want anyone to get discouraged over the last 2 users who received this compound because we believe it was probably the wrong chemical structure. I am not tooting my own horn, but simply saying that DIHEXA could be the holy grail of anti depressants and neurosteroids. I have not stumbled upon anything this promising since my interest began in nootropics 6 years ago. I have searched hundreds of research articles and never seen such promising mode of action.

Even better, this drug will most likely be extremely synergystic with other nootropics. Because it has a mode of action that is unlikely to negatively interact with anything (no MAO or reuptake acitivity) - it could potentiate other nootropics such as moodafinil greatly if it is acting basically like BDNF times ten million. Think about that guys. We are in direct contact with Dihexa researchres that due to their academic and employment status really cannot take this compound home and study it on themselves. It is very clear to SK and I that without public demand such as resulting from a successful informal trial via the group buy - this compound may be buried alive and never see light. It is up to you all to decide you want to be apart of this. I am giving everyone in the buy my own personal information. There is no funny business here. Only one person will be holding this money - and a deposit will be made for synthesis but not the whole amount. RISK will be mitigated as much as possible and you all will have complete control over this - at least as much as I have. This is a group effort - please tell your friends about this who are interested in nootropics so we can make sure we get this off the ground with the cheapest $ per gram while maintaining quality. We are initially only dealing with US chem companies because we want to eliminate risk as much as possible.

If I had the extra money (I am a chemistry student at the moment and have my housing and food and all paid for by student loans) I would do this myself and take the risk. SK and I are looking at this compound to enhance cognition and possibly treat various nervous system disorders and cognitive disorders like ADHD.

If this is a success, depending on patent status a company could possibly be formed with all of the group buyers as shareholders and the product could be sold. This is not our original intention because we do not know the patent status but I have business experience to make this happen. So the help we can receive from our members here is basically to gather more interest in the product.

Edited by xks201, 23 February 2014 - 09:34 PM.

[firefly]

Im interested, Jst watching to see how things pan out.

[socialpiranha]

i just wanna know why dihexa isn't being pursued by the founders of it if it really does what they say it does? if someone can answer that i'm down

[jabowery]

Here is a 15 minute cognitive test used to detect early signs of Alzheimers that some of you might want to take prior to treatment:

http://cft.foodforthebrain.org

I can't vouch for this test but merely provide it as an example of cognitive testing. You should do some kind of cognitive testing _before_ treatment with anything you think is going to enhance cognition.

[sk_scientific]

i just wanna know why dihexa isn't being pursued by the founders of it if it really does what they say it does? if someone can answer that i'm down

The principal researchers are continuing to pursue it at Washington State University. I think I mentioned earlier that Dr. Harding and Dr. Wright both stated that they're currently finishing up new publications on the molecule which will be in journals later this year.

The work that has brought the molecule into existence has been apparently ongoing since the 1990's. It's my undestanding that until recently it's been a matter of funding that's prevented it from going to human trials, but it's possible (as I do not know the specifics of the forthcoming publications) that they've begun the process there as well (that is beyond animal testing).

[sparkk51]

Sorry for my lack of contributions to, not only this group buy, but all buys in general. I am too intimidated and incompetent when it comes to endeavors such as these. Yet, even with that said, I agree with xks that finding a good lab should be most important (try to make the cost reasonable, not as cheap as possible). I also think 3rd party lab testing should be an absolute must.

[sk_scientific]

I just want to say guys - I think SK and I have discovered why the last 2 users of Dihexa (and only 2 users known to us) did not see results. We believe they may have been using a chemical structure which was inaccurate and posted by some academic online.

Yes, it seems fairly clear that they had a botched synthesis in spite of their confidence that they had the real deal in their possession.

[sk_scientific]

Sorry for my lack of contributions to, not only this group buy, but all buys in general. I am too intimidated and incompetent when it comes to endeavors such as these. Yet, even with that said, I agree with xks that finding a good lab should be most important (try to make the cost reasonable, not as cheap as possible). I also think 3rd party lab testing should be an absolute must.

Agreed. Plus one. And it doesn't matter if you didn't contribute before. You just did.

[xks201]

Just waiting to hear back from several individuals on chem lab recommendations...will contact several now.

[xks201]

So guys basically our quotes are coming back very high $14k+ from foreign labs, $20k+ from local labs. I have been trying to contact HappyPhysicist via skype and Xenix via PM (Xenix was active yesterday on the forum but I have not heard a response) on how they obtained their dihexa. If we can get their lab info we can synthesize the product (with possible structure corrections) for cheaper most likely. I am also in touch with another person who has synthesized it before in attempts to obtain it for cheaper. As I see it now given the dosing requirements I do not see how it can be economically synthesized so if these avenues do not pan out I am going to have to hand over the torch to whoever wants it. Hopefully one of of these three people can direct us to cheap Dihexa.

[Azz19]

How many grams are these quotes for?

[xks201]

100g - 30mg/day is what we estimated as a daily dose.

Edited by xks201, 27 February 2014 - 05:11 PM.

[megatron]

You can just give up contacting Xenix, he isn't going to respond anyway. He completely stopped posting and answering PM's after he got his FGL. Maybe the latter could be a hint as to why? According to he's profile though, he is active almost every day.