1569 replies to this topic

[Xenix]

does anyone have the peptide sequence ?

The structure is generally spoken of as 'hexanoic acid-Tyr-Ile-(6)amino-hexamide'. (Ref.) Whether or not the hype surrounding Dihexa is warranted remains to be seen.
GABA-Tyr-Ile was studied alongside Dihexa, and also had really interesting pro-cognitive effects. It, too, had a long half-life and decent serum stability. It might also be worth some effort to synthesize and experiment with.

Pretty sure Dihexa was chosen over all the other angiotensin analogues because it showed the highest oral bioavailability (hydrophobicity).

[Xenix]

edit: double post again (sorry)

Edited by Xenix, 28 March 2013 - 10:16 AM.

[nootlyinclinded]

Rofl,
It is interesting that others want to get this peptide synthesized as well. Anyways, I've been noticing this sort of manic personality going on. I am better able to perceive and interpret another person's body language; moreover, I am able to see and detect a person's microexpressions. I am more inclined now to hearing changes in a person's tone of voice and how that correlates to their internal emotional state. Simply, I am more aware of things now. I am constantly thinking and plotting now.

nootlyinclinded, thanks for sharing your experiences with dihexa here. Have you attempted reading and memorizing information while "on" dihexa? If so, was your memory capacity/learning speed improved as compared to when you're not taking anything?

I read everyday; however, I have not noticed if dihexa has improved my memory. Even so, I would like to note that I am making more connections to things. To clarify, when a person pictures an orange, they may associate the tree that it came from, the annoying seeds they have to spit out, and so on. When I picture an orange now, I make much more associations and that in itself, may help with memory although it is somewhat hard for the guinea pig to quantify his own subjective feelings. Things seems much easier now. Obstacles don't seem too daunting or impossible to over come. Despite the relative ease that things seem to be now, I have not noticed any change in motivation. Homework is still has hard to start.

[IA87]

I wonder if there is any test you can take that will show these changes you are going through without the practice effect interfering too much. What tests does the Dihexa paper employ?

[jabowery]

I wonder if there is any test you can take that will show these changes you are going through without the practice effect interfering too much. What tests does the Dihexa paper employ?

A control subject who takes the same tests is needed.

If nothing else the Word Sum Puzzle is easy to do repeatedly and what it tests is well characterized from its use in the GSS.

Edited by jabowery, 29 March 2013 - 01:58 AM.

[HenryHH]

Is there an online supplier that regularly sells dihexa? If so, where can I order it? Thanks...

[Olon]

I am better able to perceive and interpret another person's body language; moreover, I am able to see and detect a person's microexpressions. I am more inclined now to hearing changes in a person's tone of voice and how that correlates to their internal emotional state. Simply, I am more aware of things now. I am constantly thinking and plotting now.

If Dihexa should really have an acute anti-autistic effect the synapse formation would be a downside for this application because autistic persons have an excess of synapses anyway.

[Reformed-Redan]

This is a very interesting peptide. After the PRL-8-53 thread I hope to join any group buy possible with this peptide which is active at picomoles(!)

[Izan]

i have my eyes on this too. please start a group buy after the prl 8-53.

[Xenix]

Anyone want to speculate whether or not this should be taken on an empty or full stomach?
and
What time of day/night would be best to take a dose?

[Major Legend]

Rofl,
It is interesting that others want to get this peptide synthesized as well. Anyways, I've been noticing this sort of manic personality going on. I am better able to perceive and interpret another person's body language; moreover, I am able to see and detect a person's microexpressions. I am more inclined now to hearing changes in a person's tone of voice and how that correlates to their internal emotional state. Simply, I am more aware of things now. I am constantly thinking and plotting now.

nootlyinclinded, thanks for sharing your experiences with dihexa here. Have you attempted reading and memorizing information while "on" dihexa? If so, was your memory capacity/learning speed improved as compared to when you're not taking anything?

I read everyday; however, I have not noticed if dihexa has improved my memory. Even so, I would like to note that I am making more connections to things. To clarify, when a person pictures an orange, they may associate the tree that it came from, the annoying seeds they have to spit out, and so on. When I picture an orange now, I make much more associations and that in itself, may help with memory although it is somewhat hard for the guinea pig to quantify his own subjective feelings. Things seems much easier now. Obstacles don't seem too daunting or impossible to over come. Despite the relative ease that things seem to be now, I have not noticed any change in motivation. Homework is still has hard to start.

If these effects are anything to go by, then Dihexa would make healthy individuals smarter and more like a genius, but not necessarily more successful and productive. Too many associations make higher level thinking easy, but concentration on easy things like simple conversation and eye contact exceedingly hard. I know this because I was like this prior to my cerebral accident, it was like ADHD but everything you ever think is very thoughtful, very relevant and useful. Still without some kind of determination and motivation, these thoughts are all they are, thoughts. Thoughts that gets hidden away and forgotten on some notepad.

Unless your intelligence is average or below average, i'm not really sure these effects would help studying for traditional exams either. Exams are more about repetition and memory, requiring some level of abstract/contextual understanding, but not excessive to the point of questioning material or creating new material, therefore I would say Dihexa would probably make studying harder rather than easier.

I wonder if these effects will stay permanent upon your cessation of Dihexa. That could be a good or bad thing.

[sparkk51]

Rofl,
It is interesting that others want to get this peptide synthesized as well. Anyways, I've been noticing this sort of manic personality going on. I am better able to perceive and interpret another person's body language; moreover, I am able to see and detect a person's microexpressions. I am more inclined now to hearing changes in a person's tone of voice and how that correlates to their internal emotional state. Simply, I am more aware of things now. I am constantly thinking and plotting now.

nootlyinclinded, thanks for sharing your experiences with dihexa here. Have you attempted reading and memorizing information while "on" dihexa? If so, was your memory capacity/learning speed improved as compared to when you're not taking anything?

I read everyday; however, I have not noticed if dihexa has improved my memory. Even so, I would like to note that I am making more connections to things. To clarify, when a person pictures an orange, they may associate the tree that it came from, the annoying seeds they have to spit out, and so on. When I picture an orange now, I make much more associations and that in itself, may help with memory although it is somewhat hard for the guinea pig to quantify his own subjective feelings. Things seems much easier now. Obstacles don't seem too daunting or impossible to over come. Despite the relative ease that things seem to be now, I have not noticed any change in motivation. Homework is still has hard to start.

If these effects are anything to go by, then Dihexa would make healthy individuals smarter and more like a genius, but not necessarily more successful and productive. Too many associations make higher level thinking easy, but concentration on easy things like simple conversation and eye contact exceedingly hard. I know this because I was like this prior to my cerebral accident, it was like ADHD but everything you ever think is very thoughtful, very relevant and useful. Still without some kind of determination and motivation, these thoughts are all they are, thoughts. Thoughts that gets hidden away and forgotten on some notepad.

Unless your intelligence is average or below average, i'm not really sure these effects would help studying for traditional exams either. Exams are more about repetition and memory, requiring some level of abstract/contextual understanding, but not excessive to the point of questioning material or creating new material, therefore I would say Dihexa would probably make studying harder rather than easier.

I wonder if these effects will stay permanent upon your cessation of Dihexa. That could be a good or bad thing.

Let's not get ahead ourselves here

[Xenix]

www.youtube.com/watch?v=U4cF_ND4Ld4

Watch from 10:10-11:30; they put hippocampal cells and Fibroblast Growth Factor (FGF) together in an in-vitro dish, did a dose-response curve, and found that beyond a certain concentration, the FGF switched from an 'axon growing mechanism' and into proliferation (carcinogenic?) qualities.

I'm wondering if Dihexa could have the same kind of sensitivity to the dose-response curve as FGF does... The *possibility* of Dihexa causing cancer has already been discussed fairly in-depth in pages 1-2 of this thread, but the other possibility of a highly sensitive dose-response curve is pretty concerning, too.

Check this out for a closer look at what the C-Met receptor is and does: www.youtube.com/watch?v=bvMYz_Oq_vg

[sunshinefrost]

Hi nootlyinclined,

You've taken cerebrolysin, how would you compare it to it ? I feel supercharged (but calm) and extremely clear on cere, are you seing the same on this new noot ? How is your working memory compared to the pre-dihexa ?

Thanks and good luck

[nootlyinclinded]

Hi nootlyinclined,

You've taken cerebrolysin, how would you compare it to it ? I feel supercharged (but calm) and extremely clear on cere, are you seing the same on this new noot ? How is your working memory compared to the pre-dihexa ?

Thanks and good luck

I'd have to say that Dihexa is way better than cerebrolysin. With cerebrolysin, I did not feel much at all. The effects were very very subtle to the point that it did not produce much at all. I'd have to say that cerebrolysin is not worth the amount of money one has to spend. Although I have to say that cerebrolysin is very effective in increasing your social abilities and so forth. However, I would have been perfectly fine with my noopept, oxiracetam, piracetam, alpha-GPC, and ALCAR.

[HenryHH]

nootlyinclinded, have you attempted to read something (e.g., educational material, homework, whatever) and then test your recall ability? Has it turned you into one of those guys who can read something once and then remember it forever?

[hadora]

nootlyinclinded, have you attempted to read something (e.g., educational material, homework, whatever) and then test your recall ability? Has it turned you into one of those guys who can read something once and then remember it forever?

I don't think Dihexa can give you the "perfect memory",but it is highly probable that it will increase it like it was seen on poisoned and old rats
the difference between Dihexa and other nootropics is that any gain on it is probably permanent so you don't have to take it indefinitely like other compounds

Edited by hadora, 31 March 2013 - 08:21 AM.

[hadora]

Figure 3: Dihexa reverses scopolamine-dependent spatial learning deficits.

Group latencies to find the submerged platform in the Morris water maze task of spatial memory are shown.
20 minutes before beginning testing 3 month old male Sprague Dawley rats were given scopolamine directly into the brain (icv) and 15 minutes later dihexa was given either icv, intraperitoneally (ip), or orally.
There were 5 trials per day for 8 days.
The latency to find the pedestal was considered a measure of learning and memory.

A.Rats were pretreated with icv scopolamine (70 nmol in 2 μl aCSF) 20 min prior to
training followed by the icv infusion of dihexa (0.1 or 1 nmol in 2 μl aCSF) 5 min prior to daily training.

A two-way ANOVA with repeated measures indicated that all time points for the 1nmol dihexa group
were different from the scopolamine group, which received vehicle (aCSF) instead of dihexa (***p<.001).

The lower, 0.1nmol, dose of dihexa was also significantly improved performance when compared to the scopolamine
group on days 5-8 of testing (*p<.05).

B. Rats were pretreated with icv scopolamine (70 nmol in 2 μl aCSF) 20 min prior to training
followed 15 minutes later by an ip injection of dihexa in DMSO (<1%) at .05mg/kg, .25mg/kg, or .50mg/kg.
A two-way ANOVA with repeated measures indicated that the latency curves for dihexa at .25mg/kg and
.50mg/kg were different than the scopolamine&#9658;aCSF group’s learning curve
(***p<.001). The .50mg/kg group was not different than the vehicle control group
(p>.05) while the .05mg/kg dihexa group was not different than the scopolamine group (p>.05).

C. Rats were pretreated with icv scopolamine (70 nmol in 2 μl aCSF) 20 min
prior to training followed by oral delivery (gavage) of dihexa at 1.25/kg and 2.0mg/kg .25mg/kg (suspension in isotonic NaCl), 5 min prior to daily training.
The high oral (2 mg/kg) dose of dihexa completely reversed the scopolamine-dependent learning deficit
(***p<.001) while the effect of scopolamine was partially reversed at the 1.25 kg/mg dose on days 3-8 (p<.01). aCSF= artificial cerebrospinal fluid. Mean +/-SEM; n=8-10

Edited by hadora, 31 March 2013 - 08:56 AM.

[hadora]

Figure 5: Dihexa improves spatial learning in aged rats.

Group latencies to find the submerged platform in the Morris water maze task of spatial memory are shown.
Five minutes before beginning testing 24 month old mixed sex (3 male and 3 female/group)
Sprague Dawley rats were administered dihexa (2 mg/kg) orally by gavage (suspension in isotonic NaCl), on a daily basis.
There were 5 trials per day for 8 days.
The latency to find the pedestal was considered a measure of learning and memory.

The learning curve for the treated rats was significantly different than that of the non-treated rats (Mann-
Whitney U, *p<.03). Mean+/-S.E.M.; n=6.

[hadora]

Figure 6: Nle1-AngIV and Dihexa increase the number of dendritic spines.
Time dependent effects of Nle1-AngIV and dihexa treated neurons on spinogenesis.

Hippocampal neurons transfected with mRFP-β-actin were treated with 10-12 M dihexa or
10-12 M Nle1-Ang IV for 5 days or 30 minutes in culture prior to fixation on day in vitro
12 (DIV12) .

A) Representative image of the dendritic arbor of a 5 day vehicle treated hippocampal neuron.

B) Representative image of a dendritic arbor from a neuron stimulated for 5 days with 10-12 M dihexa.

C) Representative image of the dendritic arbor of a neuron stimulated with 10-12 M Nle1-Ang IV for 5 days.

D) Bar graph representing the number of spines per 50 μm dendrite length per treatment condition following a 5 day in vitro treatment. ***p < 0.001; n = 200 dendritic segments.

E) Bar graph representing the number of spines per 50 μm dendrite length per treatment condition following an acute 30 minute treatment. ***p < 0.001; n = 60 dendritic segments. Mean ± S.E.M. Analysis by one-way ANOVA and Tukey post hoc test.

[hadora]

Facilitation of hippocampal synaptogenesis and spatial memory by C-terminal truncated Nle1-angiotensin IV analogs.

Benoist CC, Wright JW, Zhu M, Appleyard SM, Wayman GA, Harding JW.

Source

Department of Veterinary and Comparative, Washington State University, Pullman, Washington 99164-6520, USA.

Abstract


Angiotensin IV (AngIV; Val(1)-Tyr(2)-Ile(3)-His(4)-Pro(5)-Phe(6))-related peptides have emerged as potential antidementia agents. However, their development as practical therapeutic agents has been impeded by a combination of metabolic instability, poor blood-brain barrier permeability, and an incomplete understanding of their mechanism of action. This study establishes the core structure contained within norleucine(1)-angiotensin IV (Nle(1)-AngIV) that is required for its procognitive activity. Results indicated that Nle(1)-AngIV-derived peptides as small as tetra- and tripeptides are capable of reversing scopolamine-induced deficits in Morris water maze performance. This identification of the active core structure contained within Nle(1)-AngIV represents an initial step in the development of AngIV-based procognitive drugs. The second objective of the study was to clarify the general mechanism of action of these peptides by assessing their ability to affect changes in dendritic spines. A correlation was observed between a peptide's procognitive activity and its capacity to increase spine numbers and enlarge spine head size. These data suggest that the procognitive activity of these molecules is attributable to their ability to augment synaptic connectivity.

http://www.ncbi.nlm....pubmed/21719467

[hadora]

A role for the angiotensin AT4 receptor subtype in overcoming scopolamine-induced spatial memory deficits.

Pederson ES, Krishnan R, Harding JW, Wright JW.

Source

Program in Neuroscience, Washington State University, Pullman, WA 99164-6520, USA.

Abstract


There is increasing interest in the role of the brain angiotensin AT4 receptor subtype in cognitive processing. This receptor subtype is activated by angiotensin IV (AngIV), is heavily distributed in the mammalian hippocampus, neocortex, and cerebellum, and has been linked with a learning andmemory function. The present investigation utilized intracerebroventricular (i.c.v.)-infused scopolamine hydrobromide (scop), a muscarinic receptor antagonist, to disrupt acquisition of the circular water maze task of spatial memory. All animals received 2 days of training trials (five trials/day) using a visible platform in an effort to preclude subsequent confounding by scopolamine-induced sensory and/or motor impairments. In the first experiment, i.c.v.-infused scopolamine (70 nmol) was followed by 0, 10, 100, or 1000 pmol i.c.v. doses of Nle(1)-AngIV in separate groups of rats. Results indicated that each dose of Nle(1)-AngIV improved the poor acquisition of this task induced by scopolamine treatment. However, the 100- and 1000-pmol doses were most effective with respect to latency and distance to find the submerged pedestal. A second experiment demonstrated that treatment with a specific AT4 receptor antagonist, Nle(1), Leual(3)-AngIV (1000 pmol), blocked the ability of Nle(1)-AngIV (100 pmol) to improve the performance of scopolamine-compromised rats. These results support the notion that hippocampal AT4 receptors are involved in spatial memoryprocessing, and that activation of these binding sites can overcome the disruption of spatial memory accompanying treatment with a muscarinic receptor antagonist.

http://www.ncbi.nlm....pubmed/11730987

Hepatocyte growth factor overexpression in the nervous system enhances learning and memory performance in mice.

Kato T, Funakoshi H, Kadoyama K, Noma S, Kanai M, Ohya-Shimada W, Mizuno S, Doe N, Taniguchi T, Nakamura T.

Source

Kringle Pharma Joint Research Division for Regenerative Drug Discovery, Center for Advanced Science and Innovation, Osaka University, Osaka, Japan.

Abstract


Hepatocyte growth factor (HGF) and its receptor, c-Met, play pivotal roles in the nervous system during development and in disease states. However, the physiological roles of HGF in the adult brain are not well understood. In the present study, to assess its role in learning and memory function, we used transgenic mice that overexpress HGF in a neuron-specific manner (HGF-Tg) to deliver HGF into the brain without injury. HGF-Tg mice displayed increased alternation rates in the Y-maze test compared with age-matched wild-type (WT) controls. In the Morris water maze (MWM) test, HGF-Tg mice took less time to find the platform on the first day, whereas the latency to escape to the hidden platform was decreased over training days compared with WT mice. A transfer test revealed that the incidence of arrival at the exact location of the platform was higher for HGF-Tg mice compared with WT mice. These results demonstrate that overexpression of HGF leads to an enhancement of both short- and long-term memory. Western blot analyses revealed that the levels of N-methyl-D-aspartate (NMDA) receptor subunits NR2A and NR2B, but not NR1, were increased in the hippocampus of HGF-Tg mice compared with WT controls, suggesting that an upregulation of NR2A and NR2B could represent one mechanism by which HGF enhances learning and memory performance. These results demonstrate that modulation of learning and memory performance is an important physiological function of HGF that contributes to normal CNS plasticity, and we propose HGF as a novel regulator of higher brain functions.
Copyright © 2012 Wiley Periodicals, Inc.

http://www.ncbi.nlm....pubmed/22535512

[hadora]

Anyone want to speculate whether or not this should be taken on an empty or full stomach?

in the study they used a suspension of dihexa in isotonic NaCl, probably on empty stomach

What time of day/night would be best to take a dose?

Doesn't matter

[megatron]

Wow hadora, after those results Dihexa looks even more promising!

[hadora]

Wow hadora, after those results Dihexa looks even more promising!

yeah it look very promising of course and easy to synth

[Major Legend]

Wow hadora, after those results Dihexa looks even more promising!

Yeah this looks beyond anything out there at the moment, in terms of synaptic generation.

[Reformed-Redan]

Wow hadora, after those results Dihexa looks even more promising!

yeah it look very promising of course and easy to synth

Are we organizing a groupbuy for this? As far as I'm concerned the PRL-8-53 groupbuy is over, :D This stuff should be cheaper, anyways. :DD

[hadora]

Wow hadora, after those results Dihexa looks even more promising!

yeah it look very promising of course and easy to synth

Are we organizing a groupbuy for this? As far as I'm concerned the PRL-8-53 groupbuy is over, :D This stuff should be cheaper, anyways. :DD

yeah it will be a good idea but we should wait until people finish their experimentation with PRL 8 53

[sunshinefrost]

How does a group buy work. I would like in if possible.

[Hebbeh]

I'm highly interested and would be in for a group buy. I've already contributed to the PRL-8-53 group buy but it seems to be falling apart due to suddenly too many getting cold feet? As interesting as PRL-8-53 seems, I would be more interested in the long term effects of Dihexa.