• Log in with Facebook Log in with Twitter Log In with Google      Sign In    
  • Create Account
  LongeCity
              Advocacy & Research for Unlimited Lifespans

Photo
* * * * * 2 votes

FGL - NCAM-derived FGF peptide sparks synaptic plasticity, promotes LTP, and improves memory in rodents

fgl ltp ncam synaptic plasticity peptide

  • Please log in to reply
76 replies to this topic

#61 Ceretropic

  • Guest
  • 86 posts
  • 55
  • Location:Phoenix AZ

Posted 10 April 2014 - 08:14 PM

Great one !

 

But are You certain that those peptides are responsible for the Cerebrolysin effect i.e. activating the Hedgehog pathway ?

And what about the remaining peptides, what are their effects ?

 

 

Well I am going off research from chrono from 2010. He found a lot of information by going through Ebewe's patents, which state that there are 3 main peptides that are leading to the effects. I am still researching deeper into it, but the evidence seems pretty good.

 

 

Great! Does this mean that you are planning to stock it? If so, I am excited. How long do you think it will take to have it synthesized and available for purchase?

 

That is the plan. If I can get enough people interested, I could probably have it within 3 weeks of giving the go ahead to my lab.


Edited by Ceretropic, 10 April 2014 - 08:15 PM.


#62 Megatrone

  • Guest
  • 606 posts
  • 79
  • Location:Norway
  • NO

Posted 10 April 2014 - 08:42 PM

Interested as well.



sponsored ad

  • Advert
Click HERE to rent this advertising spot for BRAIN HEALTH to support LongeCity (this will replace the google ad above).

#63 ceridwen

  • Guest
  • 1,285 posts
  • 95

Member Away
  • Location:UK

Posted 11 April 2014 - 03:35 AM

Interested

#64 Flex

  • Guest
  • 1,629 posts
  • 141
  • Location:EU

Posted 11 April 2014 - 06:29 AM

I might be interrested in the 3 Cerebrolysin peptides, If the quality is ensured enough. Since its supposed to be injected.

Perhaps some guys in the Cerebrolysin thread might be interrested as well.

 

In regards to FGL, I became a bit concerned when I read this:

http://www.ncbi.nlm....pubmed/24456603

 

Could somebody explain me whethever this is means either good or bad:

These data suggest that FGL administration might have an impact on disease-associated alterations in the hippocampal neuronal progenitor cell population.

 

Edit: Fuck it, I´m in for FGL

 

 


Edited by Flex, 11 April 2014 - 07:05 AM.


#65 Ceretropic

  • Guest
  • 86 posts
  • 55
  • Location:Phoenix AZ

Posted 11 April 2014 - 10:48 PM

That article is too new for me to get full access to yet. However, the abstract does state:

 

 

Whereas the low dose of FGL did not affect this kindling-associated alteration, 10 mg/kg FGL proved to attenuate the expansion of the doublecortin-positive cell population.

 

Since we are going to be using 250mcg, it would seem that might not be an issue. I'll see if I can get someone to get me the full paper so I can read more about it.



#66 malbecman

  • Guest
  • 729 posts
  • 152
  • Location:Sunny CA

Posted 11 April 2014 - 11:15 PM

 I can get you the article......I will be offline this weekend (like in 15 minutes!!) so I can prolly due it on Monday.  PM me.

 

 

That article is too new for me to get full access to yet. However, the abstract does state:

 

 

Whereas the low dose of FGL did not affect this kindling-associated alteration, 10 mg/kg FGL proved to attenuate the expansion of the doublecortin-positive cell population.

 

Since we are going to be using 250mcg, it would seem that might not be an issue. I'll see if I can get someone to get me the full paper so I can read more about it.

 



#67 Ceretropic

  • Guest
  • 86 posts
  • 55
  • Location:Phoenix AZ

Posted 11 April 2014 - 11:20 PM

Someone just got me the full study. I will read it over shortly.


Edited by Ceretropic, 11 April 2014 - 11:21 PM.


#68 telight

  • Guest
  • 173 posts
  • 47
  • Location:USA, VA

Posted 11 April 2014 - 11:22 PM

That article is too new for me to get full access to yet. However, the abstract does state:

 

 

Whereas the low dose of FGL did not affect this kindling-associated alteration, 10 mg/kg FGL proved to attenuate the expansion of the doublecortin-positive cell population.

 

Since we are going to be using 250mcg, it would seem that might not be an issue. I'll see if I can get someone to get me the full paper so I can read more about it.

 

I sent you a PM. Also:

 

. Furthermore, when the authors blocked NMDA receptors, which are crucial for LTP, FGL treatment no longer pumped up AMPA receptor delivery. Esteban notes that this activity dependence is critical for a cognitive enhancer. If the peptide indiscriminately increased synaptic transmission, it might overexcite neurons and lead to epilepsy, he said. But by heightening synaptic plasticity only in response to activity, the peptide helps the animal encode information more easily, leading to better memory.

→ source (external link)

 

This researcher doesn't seem to worried about the risk of epilepsy, but due diligence is always a good thing when it comes to these things.


Edited by telight, 11 April 2014 - 11:23 PM.


#69 Overman

  • Guest
  • 31 posts
  • 5
  • Location:Dallas, Texas

Posted 13 April 2014 - 02:23 AM

Very interested as well. 



#70 Ceretropic

  • Guest
  • 86 posts
  • 55
  • Location:Phoenix AZ

Posted 13 April 2014 - 09:41 AM

After reading through the study, I am not too worried about it either

 

I am very close to pulling the trigger on the FGL order. I just don't want to be stuck with a bunch of vials of peptides that require a higher dosage than economically feasible, because I went off two anecdotes from people I do not know.

 

I have dug into studies a little deeper. In one study, they injected 5mcg into rats and found statistical improvements. The rats weighed 165g grams. So we can calculate their dosage as 30mcg/kg. If we correct that for allometric scaling, that leaves us with a human dosage of 4.8mcg/kg. That would be just under 400mcg for my body weight per day. Now those dosages were intracerebroventricularly injected, so I am not sure how much loss in efficiency we are going to see through the blood brain barrier. However, at least we are now in the ballpark with dosages. One other tasty tidbit of information was that the FGL source they used was 85% pure. Ours is going to be 99% pure, so that should make it more potent.

 

Digging a little further into it, I found another study that used subcutaneous injections on rats weighing 250g. They used .9mg/kg, 2.7mg/kg, and 8mg/kg dosages. Both the 8mg/kg and 2.7mg/kg dosages showed statistical improvements in memory, while there was no effect at the .9mg/kg. Those dosages correspond to .14mg/kg, .43mg/kg, and 1.3mg/kg in humans. So the equivalent dosage of 11mg for my body weight showed no effects in rats, while 35mg and 105mg did. Now that is in rats, so it might not correspond perfectly. However, 250mcg is looking a little low by my calculations.

 

That same study did look at the effect of intranasal and sub-Q administration on plasma concentration, and found that FGL rapidly passes the blood brain barrier, and is extremely stable, being found in plasma for up to 5 hours after injection. Furthermore, improvements in social memory lasted for 73 hours after administration! So this seems like a very effective and long lasting peptide if we can get the dosages correct.

 

Then there was a human study that used intranasal administration of 25mg, 50mg, and 100mg. The issue is that they only detected FGL in plasma for the 50mg and 100mg dosages. The 25mg dosage was undetectable. They did reference another study that showed intranasal administration in dogs did not lead to measurable increases in plasma concentration, but that subcutaneous administration did. So perhaps the lower dosages will work sub-Q, while not intranasal. But 250mcg? I don't know...

 

They also state this:

 

 

This dose range was selected for investigation as it approximates to the expected minimal effective dose and the highest well tolerated or feasible dose in humans, based on projections of data collected in pharmacological experiments in rodents.

 

Since I am coming up with very similar numbers to they are on my own research, I would imagine that the estimations are fairly accurate. If that is the case, the 250mcg dosage is looking unlikely. The one weird thing is that human intranasal dosages did not reach peak plasma levels until 1 hour after administration. This is in contrast to the 10 minutes we saw with subcutaneous in rats. Perhaps the subcutaneous is a lot more efficient than intranasal in humans. But is it orders of magnitude more efficient?

 

I don't know guys, two anecdotes are not much for me to go on here; especially when they are contradicting the numbers I am coming up with. I don't want to be rude, but are PAM2 and Xenix trusted people around here? I really want to believe, but my logic is sounding off alarms in my head.

 

Thoughts?


  • like x 2

#71 Flex

  • Guest
  • 1,629 posts
  • 141
  • Location:EU

Posted 13 April 2014 - 12:30 PM

If its about something important like now, I would take everthing with a grain of salt.

I´ve tried allready to contact Xernix, but He didnt respond, which seems strange to me...

 

So if You ask me, math is math and subjective reports are subjective reports.

( no offence or something to the prevorious users !)

 

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

 

Correct me if I´m wrong. But that are seemingly bad News, when the dose has to be 400mg

and in the very best case (regarding to Veritas incoruptus) 1 shot would be about 200 $.  Since 2$=1mg

 

----------

 

Btw, here is an interresting compound what I´ve found

Thymosin Beta 4

http://www.longecity...knownunderated/


Edited by Flex, 13 April 2014 - 12:52 PM.

  • like x 1

#72 VERITAS INCORRUPTUS

  • Guest
  • 257 posts
  • 30
  • Location:Omnipresent-Antipresent

Posted 13 April 2014 - 03:49 PM

Thoughts?
 
^^ The studies very much denote a very! high dosing requirement...pure and simple...


#73 Ceretropic

  • Guest
  • 86 posts
  • 55
  • Location:Phoenix AZ

Posted 13 April 2014 - 11:23 PM

Yeah, sorry to be the bearer of bad news. I just do not want to bring out a product that is wildly under-dosed. It seems that by my calculations, active human dosages start around 35mg, with 100-200mg being the strongest.

 

It seems like an awesome peptide, and remains active for 3 days. So I am going to keep trying to figure out a way to make it work. My lab did not give me much discount for larger dosages. I had them go all the way up to 100mg/vial in case we found out dosages were much higher. I would have to charge a ton at the price they are giving me. Nobody would pay over $400 for 3 light doses or one normal dose. But I am not going to give up just yet.

 

During my marathon research session, I did find some more promising peptides that stemmed from research around FGL and Cerebrolysin. So I am going to look more into those as well. For now our subcutaneously injected SEMAX is going to have to do. It's one of the most potent nootropics I have tried, and is what really got me looking into peptides more. I even have a nasal spray version that I created as a proof of concept right next to me. So far so good. It should be released soon.

 

So I am going to say no to the 5mg vial order. I don't want to waste people's money and time.


  • like x 3

#74 Flex

  • Guest
  • 1,629 posts
  • 141
  • Location:EU

Posted 14 April 2014 - 01:03 AM

Yeah, sorry to be the bearer of bad news. I just do not want to bring out a product that is wildly under-dosed. It seems that by my calculations, active human dosages start around 35mg, with 100-200mg being the strongest.

 

It seems like an awesome peptide, and remains active for 3 days. So I am going to keep trying to figure out a way to make it work. My lab did not give me much discount for larger dosages. I had them go all the way up to 100mg/vial in case we found out dosages were much higher. I would have to charge a ton at the price they are giving me. Nobody would pay over $400 for 3 light doses or one normal dose. But I am not going to give up just yet.

 

During my marathon research session, I did find some more promising peptides that stemmed from research around FGL and Cerebrolysin. So I am going to look more into those as well. For now our subcutaneously injected SEMAX is going to have to do. It's one of the most potent nootropics I have tried, and is what really got me looking into peptides more. I even have a nasal spray version that I created as a proof of concept right next to me. So far so good. It should be released soon.

 

So I am going to say no to the 5mg vial order. I don't want to waste people's money and time.

 

Aynway, Thank You for the effort Ceretopic.

 

Could You please tell me some interresting peptides which You did find.

Its not easy for me to find some, and Dihexa seems not to be a option for me since e.g. its pathway is somehow implicated in cancer growth etc.
 


Edited by Flex, 14 April 2014 - 01:49 AM.


#75 Ceretropic

  • Guest
  • 86 posts
  • 55
  • Location:Phoenix AZ

Posted 14 April 2014 - 02:37 AM

The most promising one that I found is actually a derivative of one of the main peptides in Cerebrolysin. They found that Cerebrolysin reacts with neutralizing antibodies to human CNTF, GDNF, IGF-1 and IGF-2. However, they found that specifically neutralizing CNTF inhibited the neurogenic properties of cerebrolysin. So that led them to target CNTF itself.

 

They used epitope mapping of the antibodies that neutralized CNTF, and found that peptide (Ac-VGDGGLFEKKL-NH2) enhanced hippocampus-dependent learning, memory, neurogenesis, and increased neuronal plasticity in normal adult mice. However, that peptide had difficulty crossing the BBB in meaningful amounts, and was broken apart quickly by enzymes, so they decided to alter the structure by adding adamantane building blocks to make it more lipophyilic, and to shield it from enzyme degradation. Rather than modifying the complete structure, they took the most active sub-sequence of it (Ac-DGGL-NH2), then added the adamantane structures off the C-terminus, or both the C and N termini. This created two peptides that are active when administered peripherally.

 

The two peptides are Ac-DGGLAG-NH2 and 1-AdCO-DGGLAG-NH2 . The more active version of the two is (Ac-DGGLAG-NH2), also known as P21. They think the extra adamantane moeity instead of the smaller N-acetyl group at the N-terminus, probably prevented a proper interaction of the active DGGL subsequence with its receptors. So it looks as though P21 is superior to P22. All the dosages are in nM, though. So I have to research more on converting it to mcg, then scaling it to humans.

 

I also found a cool modification to SEMAX that will double its plasma half life, and increase its affinity for its receptors in the brain! Still working on that one too.


Edited by Ceretropic, 14 April 2014 - 02:47 AM.

  • like x 1

#76 Flex

  • Guest
  • 1,629 posts
  • 141
  • Location:EU

Posted 14 April 2014 - 03:09 AM

Thanks.

 

Did You find some apart from the Cerebrolysin peptides, like Thymosin Beta 4 ?

 

I might of course be interrested in the Cerebrolysine peptides as well, if they aren´t too expensive.



sponsored ad

  • Advert
Click HERE to rent this advertising spot for BRAIN HEALTH to support LongeCity (this will replace the google ad above).

#77 Ceretropic

  • Guest
  • 86 posts
  • 55
  • Location:Phoenix AZ

Posted 14 April 2014 - 03:33 AM

I have not looked into Thymosin Beta 4 too much yet. My brain has been consumed with the others. I'll see what I can find on it when I have some time, though.


  • like x 1





Also tagged with one or more of these keywords: fgl, ltp, ncam, synaptic, plasticity, peptide

0 user(s) are reading this topic

0 members, 0 guests, 0 anonymous users