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FASORACETAM

fasoracetam adhd racetam ns-105 lam-105 nsn

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#1 UltraCitron

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Posted 28 March 2014 - 12:32 AM


FASORACETAM (aka NS-105 or LAM-105) is "a high-potency nootropic drug of the racetam family."

 

 

There is not much in the literature about this racetam, but I will share what little I can find.

 

Any speculation about structural activity relationship is very welcome!!

 

First thing I feel a compulsion to do would be to switch out that cyclohexane with a phenyl group ;)

 

There is not much info under "Fasoracetam" all I could find was:

 

 

Dr. Hakonarson’s talk highlighted his work with a fasoracetam, adrug that was originally developed by the Japanese pharmaceuticalcompany Nippon Shinyaku to treat Alzheimer’s disease but, afterbeing put through clinical trials, was shelved for efficacy reasons.Dr. Hakonarson and his team are currently investigating whether fasoracetam could be used to treat ADHD, a project he called a“representation of what genomics is offering."

 

until I realized its other name is NS-105... see below

 

RESOURCES

STUDIES

  • Pharmacokinetics of NS-105 (1999)
     
  • Role of metabotropic glutamate receptor subclasses in modulation of adenylyl cyclase activity by a nootropic NS-105.
    • "In rat cerebrocortical membranes, the inhibitory action of NS-105 (0.1 microM) on forskolin-stimulated cAMP formation was blocked by a group II mGlu receptor antagonist, (+/-)-alpha-ethylglutamic acid, and by a group III antagonist, (+)-2-amino-2-methyl-4-phosphonobutanoic acid (MAP-4), but not by a group I antagonist, (+/-)-1-aminoindan-1,5-dicarboxylic acid (AIDA), whereas the facilitation of cAMP formation by NS-105 (1 microM"

      -This study suggests Fasoracetam is possibly an mGluR 2/3 agonist or PAM?
  • Clarification for previous study.! A novel cognition enhancer NS-105 modulates adenylate cyclase activity through metabotropic glutamate receptors in primary neuronal culture.
    • Conversely, in pertussis toxin-pretreated neurons, NS-105 (10(-7)-10(-5) M) significantly enhanced the forskolin-stimulated cyclic AMP formation, and this action was completely reversed by cholera toxin.
       
    • These findings suggest that NS-105 stimulates metabotropic glutamate receptor subclasses that are coupled both negatively and positively to adenylate cyclase, but it acts as an antagonist at the receptor subclasses that are linked to phosphoinositides hydrolysis.

    • It Modulates cAMP
  • Involvement of cholinergic and GABAergic systems in the reversal of memory disruption by NS-105, a cognition enhancer.
    • "NS-105 showed antiamnestic actions in a variety of animal models of cholinergic dysfunction employed in this study.
    • NS-105 (10 mg/kg) showed the increase of ACh release from the cerebral cortex and the enhancement of HACU (so coluracetam is NOT the only HACU enhancer) both in the cerebral cortex and hippocampus
    • NS-105 also reversed memory disruption induced by baclofen, a potent GABA(B) receptor agonist, but all of reference drugs did not. These results suggest that antiamnestic action of NS-105 is due to the facilitation of cholinergic neuronal activity and the suppression of GABA(B) receptor-mediated responses."
       
  • Effect of a novel cognition enhancer NS-105 on learned helplessness in rats: possible involvement of GABA(B) receptor up-regulation after repeated treatment.
    • "Biochemical data showed that repeated administration of NS-105 increased the number of GABA(B) receptors in rat cerebral cortex without affecting the binding properties of beta-adrenoceptors and 5-HT2 receptors. In contrast to other antidepressants, NS-105 did not inhibit monoamine uptake in vitro, nor did it change monoamine concentrations in brain tissues or extracellular fluids. These findings suggest that NS-105, which lacks an effect on monoaminergic systems, has potent antidepressant activity, which may involve up-regulation of GABA(B) receptors after repeated administration."

       
    • **In theory... Fasoracetam may reverse phenibut/baclofen/GHB/GBL tolerance, and its withdrawal could be the opposite of the aforementioned chemicals. This means fasoracetam will not be acutely anxiolytic but will likely induce anxiolysis with long-term administration. Awesome! I have been looking for a compound like this for years!
  • It also seems to have a ridiculously short half life. Perhaps it has active metabolites, though.

 

It is frequently mentioned in studies alongside Piracetam, Phenylpiracetam, Nebracetam, Rolziracetam, Nefiracetam, Levetiracetam, Etiracetam, Pramiracetam, Oxiracetam, Luracetam, Aniracetam, Coluracetam, Brivaracetam, Seletracetam, and Rolipram. (There are some leads in this list :laugh: )

 

In summary, this guy looks highly promising for specific purposes. However, more studies are really needed, and the toxicity information I could (not) find was paygated. :sad: Small adjustments to the molecule could be made to enhance its beneficial properties and greatly increase its half life.

 

 

 


Edited by katuskoti, 28 March 2014 - 12:35 AM.

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#2 YOLF

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Posted 28 March 2014 - 03:59 AM

What adjustments are you suggesting?
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#3 arcticjoe

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Posted 28 March 2014 - 08:29 AM

What adjustments are you suggesting?



make it cheaper and more available ;)
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#4 Babychris

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Posted 28 March 2014 - 12:10 PM

Racetams sucks... You are just some compulsive and obsessed buyers getting their need by the search of new stuff ... Honestly who came back here and said : "Wow Guy's I'm Under this XXXXX stack (a list of 20 suppléments) and it's fantastic I'm sooo happy with life, I was stupid and now I'm cured" there's is isochrome who is the biggest Joke I ever seen, a "troll" like we use to say on forum.. Guy's come on !
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#5 Mind_Paralysis

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Posted 28 March 2014 - 02:01 PM

Babychris, that may be true, that for regular, WELL people, racetams have a limited use.

HOWEVER...! For those of us with mutations to the metabotropic glutamate receptor networks, such as ADHD, this PERTICULAR version of Racetam, may be UNbelieveably benefficial.

In theory it could cut our stacks IN HALF!!

I'm not joking. In half. Do you have any idea how awesome that is? To finally manipulate our GMR1-8 mutations, DIRECTLY? Correcting the chaotic signal-substances we have, almost by night?

If this works... and there's a lot suggesting it, if that norwegian dr comes through... then we may have a very good drug for balancing the GMR-network correctly.

It could help so many diseases... and the reason we know about it? All thanks to genomic research - this is applied genetics to drugs, son. This isn't the regular old HORSE-play of finding stuff on random and trying whatever you can think of, this is real medicine.

The kind of medicine we've been waiting for, for 35 years, since the genomic project started.

It could be the real deal - don't dismiss it right out of the gate.

Unless you're neurotypical of course... then it's application is highly limited, like all racetams.
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#6 p3x888

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Posted 15 May 2014 - 07:12 AM

 

What adjustments are you suggesting?



make it cheaper and more available ;)

 

 

Ask and you shall receive -

 

https://www.newstarn...fasoracetam.php


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#7 Metagene

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Posted 15 May 2014 - 07:44 AM


 

What adjustments are you suggesting?


make it cheaper and more available ;)
 
 
Ask and you shall receive -
 
https://www.newstarn...fasoracetam.php

Son of a.......Wow I guess that should do it.
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#8 p3x888

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Posted 15 May 2014 - 08:11 AM

Ok, so can we discuss dosing? I saw 10mg per kg. is that what we should start with?



#9 ScienceGuy

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Posted 15 May 2014 - 09:07 AM

Ok, so can we discuss dosing? I saw 10mg per kg. is that what we should start with?

 

Not unless you are a RAT ;)

 

The Human Equivalent Dosage (HED) for FASORACETAM by calculation works out to be = 6 (RAT Km) / 37 (HUMAN Km) x 10 (RAT dosage) = 1.62 mg/kg :)


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#10 typ3z3r0

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Posted 15 May 2014 - 09:11 AM

The HED for the 10mg/kg dose given to the rats in that study would be 1.622 mg/kg, which equates to 113.5 mg for a 70 kg human.

EDIT: Damn it! SG beat me! :P


Edited by typ3z3r0, 15 May 2014 - 09:12 AM.


#11 Nattzor

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Posted 15 May 2014 - 10:54 AM

1.62*80=129.6 mg.

 

So they're selling 2 dosages (1 not even full) for $14.50.


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#12 PWAIN

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Posted 15 May 2014 - 11:06 AM

You could buy 10g for $165. That would give you about 2 months supply. Still not super cheap but then it is a completely new product.

Edited by PWAIN, 15 May 2014 - 11:07 AM.


#13 Nattzor

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Posted 15 May 2014 - 11:10 AM

That would still be over 2 dollar per dose for a new untested compound.



#14 NilsOlav

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Posted 15 May 2014 - 11:18 AM

Racetams sucks... You are just some compulsive and obsessed buyers getting their need by the search of new stuff ... Honestly who came back here and said : "Wow Guy's I'm Under this XXXXX stack (a list of 20 suppléments) and it's fantastic I'm sooo happy with life, I was stupid and now I'm cured" there's is isochrome who is the biggest Joke I ever seen, a "troll" like we use to say on forum.. Guy's come on !

 

Isochrome, a joke? More like a legend. I read all the posts by him. People on these forums guilted him into thinking he was "manic" because they were jealous of his completely happy, worry-free mindset, and sadly he took it in and began to believe his "manic state" was a problem. I call it a serene state.


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#15 telight

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Posted 15 May 2014 - 01:07 PM

Here's some pharmacokinetics from humans. You guys nailed it. the dose used was 100mg orally.

 

Pharmacokinetics of NS-105, a novel agent for cerebrovascular disease, in elderly subjects were compared with those in younger subjects. Fourteen healthy male volunteers (7 elderly subjects aged 68-79 years and 7 young subjects aged 20-32 years) were included in the study. In a parallel group design, a tablet containing 100 mg NS-105 was administered orally after breakfast. One young subject was excluded from the pharmacokinetic analyses owing to an insufficient urine collection. The maximum plasma concentration (Cmax) was higher in the elderly (3.06 +/- 0.69 vs. 2.13 +/- 0.34 micrograms/ml, the elderly vs. the young, mean +/- SD, p = 0.0117) and area under the plasma concentration curve (AUC) was also higher in the elderly (24.6 +/- 4.4 vs. 14.4 +/- 3.1 micrograms.hr/ml, p = 0.0006). There is a tendency that time to reach Cmax was longer in the elderly (2.1 +/- 1.1 vs. 1.3 +/- 0.5 hr, p = 0.1199), and a tendency of prolongation of elimination half-life. Urinary recovery of NS-105 was less in the elderly up to 8 h after administration, while total recovery of the dose was not different in the two groups. Total clearance was reduced in the elderly (0.076 +/- 0.013 vs. 0.121 +/- 0.025l/kg/hr, p = 0.0013) and the decrease seemed to be mainly due to a decrement in renal clearance of the drug in the elderly. A significant correlation was found between renal clearance of NS-105 and creatinine clearance of each subject (r = 0.583, p = 0.0364). These observations indicate that the plasma concentration of NS-105 will increase in elderly subjects mainly due to a decrement in renal clearance of the drug. Careful observation is needed when prescribing the drug to an elderly patient.

→ source (external link)

 

I bought 2g of the stuff from NSN and will start by trying 10mg sublingually. 



#16 xsiv1

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Posted 15 May 2014 - 03:40 PM

Uh, I'm not sure if you've kept up with his most recent posts man.

All that aside, it's very interesting to me that it also shows promise as one of the very few publicly available compounds that may have the potential to upregulate Gaba B receptors. More interesting is how it's actions differ from Nefiracetam which I believe is hardly used these days.

I can't wait to read some of the anecdotal reports that will trickle in. Ever since Sunifiram, (an impulse buy I'll admit), and some of the adverse and yet long-lasting consequences/reports of it's use with any stimulants...I now wait to hear from people.

Edited by xsiv1, 15 May 2014 - 03:46 PM.

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#17 Reformed-Redan

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Posted 15 May 2014 - 03:47 PM

Interesting compound! God, love the nootropics community now. Might have to trial this when the prices drop a little.



#18 FW900

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Posted 15 May 2014 - 05:41 PM

This morning, I ordered a small amount of fasoracetam just to 'try it'. I'm looking forward to this order arriving; as katuskoti pointed out, it seems to have a lot of potential as a nootropic. If you use the coupon code 'REDDIT' you get 10% off on New Star Nootropics.


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#19 UltraCitron

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Posted 15 May 2014 - 06:24 PM

NSN now has this available!!! Who's gonna try it?


This morning, I ordered a small amount of fasoracetam just to 'try it'. I'm looking forward to this order arriving; as katuskoti pointed out, it seems to have a lot of potential as a nootropic. If you use the coupon code 'REDDIT' you get 10% off on New Star Nootropics.

 

Great, thanks! Please tell us how your trial goes and thanks for promotional code.


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#20 Phoenicis

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Posted 15 May 2014 - 08:21 PM

Baby...Chris, you've been so negative about nootropics on various threads, healthy skepticism is good, but cheer up!  

 

Racetams sucks... You are just some compulsive and obsessed buyers getting their need by the search of new stuff ... Honestly who came back here and said : "Wow Guy's I'm Under this XXXXX stack (a list of 20 suppléments) and it's fantastic I'm sooo happy with life, I was stupid and now I'm cured" there's is isochrome who is the biggest Joke I ever seen, a "troll" like we use to say on forum.. Guy's come on !

 

Awesome post there, which racetams manipulate GMR1-8 mutations indirectly? Ive got aniracetam and pramiracetam atm. Personally I don't think I'm desperate enough to pay the high price for Fasoracetam although I am tempted. 

 

Babychris, that may be true, that for regular, WELL people, racetams have a limited use.

HOWEVER...! For those of us with mutations to the metabotropic glutamate receptor networks, such as ADHD, this PERTICULAR version of Racetam, may be UNbelieveably benefficial.

In theory it could cut our stacks IN HALF!!

I'm not joking. In half. Do you have any idea how awesome that is? To finally manipulate our GMR1-8 mutations, DIRECTLY? Correcting the chaotic signal-substances we have, almost by night?

If this works... and there's a lot suggesting it, if that norwegian dr comes through... then we may have a very good drug for balancing the GMR-network correctly.

It could help so many diseases... and the reason we know about it? All thanks to genomic research - this is applied genetics to drugs, son. This isn't the regular old HORSE-play of finding stuff on random and trying whatever you can think of, this is real medicine.

The kind of medicine we've been waiting for, for 35 years, since the genomic project started.

It could be the real deal - don't dismiss it right out of the gate.

Unless you're neurotypical of course... then it's application is highly limited, like all racetams.

 


Edited by Phoenicis, 15 May 2014 - 08:25 PM.


#21 Mind_Paralysis

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Posted 15 May 2014 - 08:49 PM

Man, I'm a bit embarrassed by that post now, Phoenicis - jeesh, why'd I have to go an' write so aggressively?

Anyways, for a question such as this, I always refer to good ol' GetoutofBox on this board, he's got the goods on neuro-medicine - I believe he himself prefers Oxiracetam, and there does appear to be some effects on glutamate with that one:

 

http://examine.com/s...nts/Oxiracetam/

But here, check out his other, NON-racetam suggestions for glutamate:

 


 

If you want to target the Glutaminergic system, there are several agents that are available. Sunifiram is a good glycine receptor agonist, but I've found it to be a bit too potent for comfort. Sarcosine is a milder glutaminergic agent, acting as a mild glycine reuptake inhibitor, which to me seems like a better (and safer) target.

 

Modafinil is definitely on my list of things to try, as it has some very interesting observed activity, very diverse in it's actions, yet still mild enough to avoid severe side-effects. The only deterrent for me is the cost and difficulty obtaining in some countries (apparently Canadian customs are pretty tough on these things), unless you live in the EU or India.

 

 

Whether that's good or bad, depends on if you have high or low amounts of glutamate, seems like the jury is out on whether people with ADHD and ADD really have heightened or lowered glutamate - seems like there are cases of both.

And then it's recently been discovered that the people with ADHD and ADD that have GMR-mutations, only appear to amount to about 20% of the people afflicted with the disorder(s).

 

I definitely think it's worth a try tho', I mean, glutamate-agonists are a lot less dangerous than amphetamines or any sort of stimulant, imho. = D

 

 

(There's also a lot suggesting Modafinil affects the glutamate networks, indirectly, as it appears to raise glutamate-levels in the brain, by possibly antagonizing GABA-levels in certain sections, and apparently GABA keeps glutamate-production in check.)


Edited by Stinkorninjor, 15 May 2014 - 08:54 PM.


#22 Phoenicis

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Posted 15 May 2014 - 11:03 PM

This was published in 2001 -

 

Pyrrolidone derivatives.

www.ncbi.nlm.nih.gov/pubmed/11741647
by S Shorvon - ‎2001
 

"...Fasoracetam

This nootropic agent is not yet licensed. Its pharmacological profile differs from that of other pyrrolidones.38 It up-regulates the GABA-B receptor, stimulates cAMP formation, and shows striking positive effects in spatial memory tests in rats with induced forebrain ischaemia, and in passive and active avoidance tasks in rats with lesions in nucleus basalis magnocellularis. Its nootropism in lesioned rats is stronger than that of aniracetam. Improved performance in forced swimming and learned helplessness tasks in rats point to possible antidepressant activity also.

Early clinical studies suggest benefit, and fasoracetam is currently in phase III trials in Alzheimer's disease and in cerebrovascular disease."


Edited by Phoenicis, 15 May 2014 - 11:03 PM.

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#23 telight

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Posted 15 May 2014 - 11:53 PM

 

This was published in 2001 -

 

Pyrrolidone derivatives.

www.ncbi.nlm.nih.gov/pubmed/11741647
by S Shorvon - ‎2001
 

"...Fasoracetam

This nootropic agent is not yet licensed. Its pharmacological profile differs from that of other pyrrolidones.38 It up-regulates the GABA-B receptor, stimulates cAMP formation, and shows striking positive effects in spatial memory tests in rats with induced forebrain ischaemia, and in passive and active avoidance tasks in rats with lesions in nucleus basalis magnocellularis. Its nootropism in lesioned rats is stronger than that of aniracetam. Improved performance in forced swimming and learned helplessness tasks in rats point to possible antidepressant activity also.

Early clinical studies suggest benefit, and fasoracetam is currently in phase III trials in Alzheimer's disease and in cerebrovascular disease."

 

 

If you read the OP, there is a document linked there that says faso was determined to not be effective for Alzheimer's. This document was published in 2012. 


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#24 Phoenicis

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Posted 16 May 2014 - 12:05 AM

True, sorry I was researching fasoracetam and dihexa at the same time and got mixed up. Proof that I need the fasoracetam!

 

 

This was published in 2001 -

 

Pyrrolidone derivatives.

www.ncbi.nlm.nih.gov/pubmed/11741647
by S Shorvon - ‎2001
 

"...Fasoracetam

This nootropic agent is not yet licensed. Its pharmacological profile differs from that of other pyrrolidones.38 It up-regulates the GABA-B receptor, stimulates cAMP formation, and shows striking positive effects in spatial memory tests in rats with induced forebrain ischaemia, and in passive and active avoidance tasks in rats with lesions in nucleus basalis magnocellularis. Its nootropism in lesioned rats is stronger than that of aniracetam. Improved performance in forced swimming and learned helplessness tasks in rats point to possible antidepressant activity also.

Early clinical studies suggest benefit, and fasoracetam is currently in phase III trials in Alzheimer's disease and in cerebrovascular disease."

 

 

If you read the OP, there is a document linked there that says faso was determined to not be effective for Alzheimer's. This document was published in 2012. 

 

 


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#25 ParMatrix

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Posted 16 May 2014 - 02:02 AM

Do not pay this much for it. Wait a few weeks and other reputable suppliers will have it for less than 1/5th the price. 


Edited by ParMatrix, 16 May 2014 - 02:07 AM.


#26 Salviar

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Posted 16 May 2014 - 03:39 AM

Does this have anxiolytic potential?

#27 ScienceGuy

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Posted 16 May 2014 - 07:10 AM

That would still be over 2 dollar per dose for a new untested compound.

 

Yes, indeed. However, be reassured somewhat by the fact that economy of scale will directly the influence the existing pricing of any such compound. In other words, it is currently expensive because it is NEW and hence being manufactured in comparatively small quantities. If it transpires to be popular within the NOOTROPIC communities indubitably as demand increases so will this inevitably lead to the manufacturing of larger batch quantities; wherein, this fact combined with healthy competition from other NOOTROPIC vendors should see a significant lessening in the retail price over time.  ;)

 

That said, I always advise commencing with a TRIAL DOSE of circa 1/10 the 'normal' dose to establish how you react to a particular substance... if you react POSITIVELY (or at the very least, not NEGATIVELY) then the dosage should be gradually increased until your particular 'sweet spot' with respect to dosage is found (if any). It is always best to deduce what is the MINIMUM DOSAGE that yields the POSITIVE EFFECTS without incidence of significant ADVERSE EFFECTS. For many people their ideal dosage will be significantly LOWER than the 'normal' dosage. In which case, this would also help with regards to the COST :)  

 

Does this have anxiolytic potential?

 

YES; however, I must stress the word 'POTENTIAL' :)


Edited by ScienceGuy, 16 May 2014 - 07:13 AM.

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#28 ScienceGuy

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Posted 16 May 2014 - 07:15 AM

Here's some pharmacokinetics from humans. You guys nailed it. the dose used was 100mg orally.

 

Pharmacokinetics of NS-105, a novel agent for cerebrovascular disease, in elderly subjects were compared with those in younger subjects. Fourteen healthy male volunteers (7 elderly subjects aged 68-79 years and 7 young subjects aged 20-32 years) were included in the study. In a parallel group design, a tablet containing 100 mg NS-105 was administered orally after breakfast. One young subject was excluded from the pharmacokinetic analyses owing to an insufficient urine collection. The maximum plasma concentration (Cmax) was higher in the elderly (3.06 +/- 0.69 vs. 2.13 +/- 0.34 micrograms/ml, the elderly vs. the young, mean +/- SD, p = 0.0117) and area under the plasma concentration curve (AUC) was also higher in the elderly (24.6 +/- 4.4 vs. 14.4 +/- 3.1 micrograms.hr/ml, p = 0.0006). There is a tendency that time to reach Cmax was longer in the elderly (2.1 +/- 1.1 vs. 1.3 +/- 0.5 hr, p = 0.1199), and a tendency of prolongation of elimination half-life. Urinary recovery of NS-105 was less in the elderly up to 8 h after administration, while total recovery of the dose was not different in the two groups. Total clearance was reduced in the elderly (0.076 +/- 0.013 vs. 0.121 +/- 0.025l/kg/hr, p = 0.0013) and the decrease seemed to be mainly due to a decrement in renal clearance of the drug in the elderly. A significant correlation was found between renal clearance of NS-105 and creatinine clearance of each subject (r = 0.583, p = 0.0364). These observations indicate that the plasma concentration of NS-105 will increase in elderly subjects mainly due to a decrement in renal clearance of the drug. Careful observation is needed when prescribing the drug to an elderly patient.

→ source (external link)

 

I bought 2g of the stuff from NSN and will start by trying 10mg sublingually. 

 

Nice find TELIGHT; and BTW starting by trying 10MG SUBLINGUALLY (i.e. 1/10 the 'NORMAL' dosage) to establish how you react to this new substance is IMO without a doubt the best way forward :)
 


Edited by ScienceGuy, 16 May 2014 - 07:17 AM.


#29 8bitmore

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Posted 16 May 2014 - 11:40 AM

 

Here's some pharmacokinetics from humans. You guys nailed it. the dose used was 100mg orally.

[...]

I bought 2g of the stuff from NSN and will start by trying 10mg sublingually. 

 

Nice find TELIGHT; and BTW starting by trying 10MG SUBLINGUALLY (i.e. 1/10 the 'NORMAL' dosage) to establish how you react to this new substance is IMO without a doubt the best way forward :)

 

On the subject of sublingual administration: I have never, ever, felt anything from taking any nootropic substance sublingually*. I have a vague notion that this might be due to over-acidic spit that deactivates the compounds before they can cross the mucus membrane barrier (I got this idea from fact that alkaloids in coca leaves cannot properly be absorbed when chewing without mixing them with sodium bicarbonate, but really I have no real idea). Any pointers as to why I seem immune to sublingual uptake?

 

Also, more on topic: exciting to first reports when they come in on Fasoracetam: although I continue (from personal exp.) to view the *racetams as mostly effective at mitigating/treating existing issues rather than boosting base-line cognition on consistent basis.

 

* have tried Coluracetam, Sunifiram, Unifiram and Noopept at ~10-15mg... then stopped trying!


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#30 UltraCitron

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Posted 16 May 2014 - 07:20 PM

What the hell is the GMR1-8 gene?







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