LONGECITY

Hi, many studies claim an increased cognition after administration of pde4 inhibitors. It was already "discussed" here about rolipram, the most know compound of this classes; but his positive effect on cognition and anixity were opposed by his gastrointestinal side effects.

But there are other similar substances which gave even better results without side effects in levels able to be effective:

http://journals.plos...ne.0102449.s002

http://jpet.aspetjou...ntent/350/1/153

Look at the improvement on Object Retrieval task, from the first study; in the image you can see the improvement: easy (open bars) versus difficult tasks (black bars)

Id like to try D159797 used in the first study, but i dont know where to get it, is there someone can manage a group buy or can buy it somewhere at low cost it would be nice.

Thanks, have a nice day

https://www.prnewswi...-300550511.html

 

this (BPN14770) is another pde4d inhibitors which has been already tested in clinical 1 phase with fine results on memory and cognition even in both healthy young and elderly volunteers, and the clinical phase 2 had been aproved by fda.

 

 

in this pdf from tetra: http://tetradiscover...CTAD-102517.pdf

 

they claim even improved working memory performace after administration of BPN14770, which is really increbible since as for now there is really nothing able to improve it in healthy and young subject (expect for direct injection of something that i dont remeber in the prefrontal cortex, there was a study about it in mouse if i remeber well), and really strange since enahncing cAMP should be detrimental for WM: http://learnmem.cshl...8/554.full.html and instead lowring cAMP level in the brain enhanced WM performance in aged mouse.

 

I have just sent an email to tetradiscovery asking for more info about the result of the clinical trail, since there is very little info about it on that pdf, and some if they can explain me how did cAMP rising enhanced WM. i hope to get an answer.

 

if that should be confirmed i think ill try harder to find some other guys interested in BPN14770 even in other forum, if ill find no one ill make it synthesize just for just myself since VM is highly correlated with "smarteness", and im sure my exams would be easier with such help

if that should be confirmed i think ill try harder to find some other guys interested in BPN14770 even in other forum

 

Where would that be? LongeCity has to be your best bet for something like this.

Where would that be? LongeCity has to be your best bet for something like this.

You are right, but i think there would be other people interested in a tested nootropic with good result (if tetra can confirm with more info) even in non-nootropic related forum. I think a subreddit would be better to manage a group buy

Edit: seems that BPN14770 and D159797 are the same suabstances (https://www.medkoo.com/products/17481)
Edited by Painkillerrr, 22 April 2018 - 04:16 PM.

Im still wating for tetra email, and ill even ask about dosage they used, 10mg which is pretty high compered to the dosage used in mouse: and im just try understanding if GSK256066 could be has a good alternative to BPN14770; since it has same affinity for pde4 b/d it could have both posivite effect from:

Pde4b inhibitions have antidepressant effect, while pde4d should be a cognitive enhancer.

https://www.ncbi.nlm...les/PMC5215650/

GEBR-7b Is instead a inhibitors of pde4d unlike BPN14770 which is a nagative allosteric regulator of pde4d therefore could be easily lead to emetic side effect before achieving any postive effects.
Edited by Painkillerrr, 24 April 2018 - 10:09 AM.

Have you tried ibudilast?

Have you tried ibudilast?

Hi, thanks for the replay.

No, i have not; it seems very interesting; but since its a pan-inhibitors of pde (a peper say pde3,4,10,11 another only 4,10) it shows gastrointestinal side effects in 32% of the patient; since it resulted in some gastrointestinal side effects im pretty sure it has some effect on pd4d, which the main related to memory and cognition improvements but also to emesis. Anyway 84% reported side effects, and seems to have similar profile of rolipram (good effects on cognition but bad side effects)


https://www.ncbi.nlm...one.0182019.pdf
https://addictions.p...atory-trial.pdf
Edited by Painkillerrr, 27 April 2018 - 09:14 AM.

Hello, i have been looking to get either D159797 (BNP) or D159687; i have found only one source for the first, but its at 1g/$5950 which is too much since tetra used 10mg/20mg orally a day in its trial.

the latter can be found in many chimical site, and one of them (chinese) seems to be selling it at 785 per gram, i have sent them an email, lets see.

 

800$ would be still to much, since the dose of D159687 would still be in the range of 10-20mg orally; BUT i have done some math, making comparisons between tetra dose and the monkey study to see how much D159687 we would need to inject to have about the same effect of D159687 and BNP used orally:

 

a)to same mg equal about the same improvement in BNP and D159687. 

 

1: lets make a comparison of the 10/20mg BNP used by tetra with the data from the monkey's study:

 

they used in the tests: 0.005, 0.5 mg/kg and 1 mg/kg; converting the dosa in the middle to human using (2): H = 1 mg/kg * (12/37) = 0.3 mg/kg for human [0.5 in moneky = 0.3 human]

Comparing it with tetra trials: In the clinical trial they used 10 and 20mg that is about the same dose used in monkey: 0.3 mg/kg *70kg = 20mg. So its confirmed that 0.5mg/kg monkey = 0.3mg/kg human. {B,C}

 

2: lets compare IV to oral

 

2a) BNP and D159687 in the same dosage gave the same results. Even if plasma exposure of BNP is about *10 of D159687. So we aim to have a IV dose for humans of D159687  with the same plasma exposure of D159687 ORAL at 0.5 mg/kg MONKEY. {A}

 

as for BNP monkey study claim IV (injection) should give about the same plasma exposure using 1/5 of the oral dose. [as you can see from the photo {A}: IV of 1mg/kg = plasma exp of about 1100 nM after 2 hours, while orally 5mg/kg is about 1000 nM after 2 hours]  {A}

 

2b) for D159687 instead 1mg/kg IV = 500 nM,  after 2 hours while oral administration of 5mg/kg = 100 nM; so to have the same plasma exposure (of 100 nM) we need 0.2mg/kg IV   *PS

 

0.2 mg/kg IV = 5mg/kg ORAL

 

but we wanted 0.5mg/kg ORAL to have about the same dose used by Tetra (0.3 mg/kg Human = 0.5 mg/kg orally for monkey):

 

proportion: 0.5 / 0.2 = 5 / x

 

so  x= 0.2 / 10 = 0.02mg/kg IV MONKEY

 

now need to convert it to human:

 

HUM = 0.02 * 12/37 = 0.0064 mg/kg IV        0.0064 mg/kg is the dose we would need to IV          {C}

 

so: 0.0064 mg/kg * 70kg = 0.44 mg IV

 

IN conclusion to have the same effect of 20 mg BNP (oral) we need to inject 0.44 (or 0.22 looking at *PS) mg of D159687.

 

even if the math is not for sure right, monkey did not have any side effect with 5mg/kg ORAL, our dose (0.44 or 0.22mg) that should be equal to 0.5mg/kg oral should be widely "safe"

 

 

*PS: But its written that oral bioavailability of D159687 is "only" of 6-13%, so the is the possibility that 5mg/kg oral = about 0.1mg/kg and not 0.2 like i thought (using the figure); this can be easly explained by the fact that i have used the plasma exposure of "2hours after administration", while the max exposure for IV is about * 10 the max exposure of ORAL

 

 

A: http://journals.plos...ne.0102449.s002

B: http://tetradiscover...CTAD-102517.pdf

C: https://www.longecit...nimal-to-human/

 

 

sorry english, hope you can understand

 

Edited by Painkillerrr, 28 April 2018 - 09:10 PM.