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Ampakines!?

ampakine cx516 cx717 nootropic cortex pharm

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#61 Isochroma

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Posted 22 March 2013 - 08:17 PM

Got your Ampakines! Sunifiram and Unifiram to be exact - and cheap!

Today I received and email from Season of the TrustWe Group: Finally a trustable supplier who takes PayPal - hover your mouse over the PP link on the Payment column to see her PayPal address on the actual page - with product in stock [Sunifiram] and shortly in stock [Unifiram: Middle of April] with prices that are cheap enough for everyone to afford!

The newly-released Racetams are: Phenylpiracetam, Sunifiram, Unifiram and Coluracetam with prices that are revolutionarily affordable - with assurance of superfast delivery by fully-trackable EMS [Express Mail Service] and money-back guarantee by PayPal!

Phenylpiracetam is IN STOCK NOW FOR IMMEDIATE SHIPMENT.
Coluracetam will be in stock halfway through April 2013. [DARK PURPLE COLORED TEXT IN TABLES INDICATES FUTURE STOCK]
Sunifiram is IN STOCK NOW FOR IMMEDIATE SHIPMENT.
Unifiram will be in stock halfway through April 2013. [DARK PURPLE COLORED TEXT IN TABLES INDICATES FUTURE STOCK]

Here are the new additions to the Racetam Prices list, including the first seller for the entirely new category of Raceram: Unifiram.

Below is just an image of the new additions - this forum will not allow proper insertion of the entries without mangling them.
The actual text and links are on the page itself so please go there to find out more - click the table below for details:

Posted Image

Coluracetam is a highly active and very potent nootropic with doses of 10mg (typical) as found by forum members from ScienceGuy's test samples.

Sunifiram and Unifiram are extremely potent nootropics with doses of about 5mg per 150lbs.

The racetam titles at the top of each table are linked to their respective Wikipedia entries. Click to find out more about them

#62 Isochroma

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Posted 24 March 2013 - 09:15 PM

As of today [Version March 24.1 2013] a new and truly affordable Sunifiram vendor has been added to the Racetam Prices list - New Star Nootropics - a reseller who can ship by regular mail or Express Mail.

Prices for both shipping modes have been calculated for all sizes of product for better cost comparison.

Edited by Isochroma-Reborn, 24 March 2013 - 09:18 PM.


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#63 Reformed-Redan

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Posted 24 March 2013 - 09:30 PM

Lol we got the message Isochroma-Reborn. Thanks for keeping the racetam price list updated for all of us. If and when the PRL-8-53 custom synthesis comes to fruition I'd be interested in a group buy for IDRA-21, a very promising AMPA'kine. Just throwing it out there. Same dose as PRL-8-53 if not lower with a long half life and not that expensive to synth as other CX compounds.

Edited by redan, 24 March 2013 - 09:30 PM.


#64 Isochroma

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Posted 24 March 2013 - 10:19 PM

Sounds interesting.

IDRA-21 is in my Nootropics folder with three studies (one having a full PDF) if you want them.

#65 Isochroma

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Posted 24 March 2013 - 10:27 PM

Posted Image

Unifiram




Posted Image


IDRA-21



See the resemblance? Aside from the main structure I see two similarities and one major structural difference:

The thiadiazine group is shared: IDRA-21's nitrogens are meta while Unifiram's nitrogens are para each other.

Secondarily, IDRA-21's halogen substituent is meta Chlorine while Unifiram's is para Fluorine.

The big difference is that Unifiram's parafluorobenzene ring takes the place of IDRA-21's methyl group.

Edited by Isochroma-Reborn, 24 March 2013 - 10:36 PM.


#66 megatron

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Posted 24 March 2013 - 10:59 PM

I think we're facing a really exciting time with all these new drugs (ampakines, neuropeptides etc.).

#67 Isochroma

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Posted 24 March 2013 - 11:03 PM

I have just at this moment sent a long promotional email to New Star Nootropics thanking them for stocking Sunifiram and exhorting them to stock Coluracetam and Unifiram from the Chinese manufacturers on my list, with references to the Coluracetam Experiences page I built and the threads dealing with these molecules on this forum.

I made a good business case to them.

It has been a long, hard push but I think my years of pushing are finally yielding results, with new suppliers coming online after seeing the interest and getting the connections offered by my thorough supplier research.

#68 Reformed-Redan

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Posted 24 March 2013 - 11:54 PM

Sounds interesting.

IDRA-21 is in my Nootropics folder with three studies (one having a full PDF) if you want them.

Sure, PM the link. Thanks. Definitely worth looking into. Unifiram unlike Sunifiram increases fEPSP.

Pharmacological characterization of DM232 (unifiram) and DM235 (sunifiram), new potent cognition enhancers.

Romanelli MN, Galeotti N, Ghelardini C, Manetti D, Martini E, Gualtieri F.


Source

Dipartimento di Scienze Farmaceutiche, University of Florence, Sesto Fiorentino, Italy. novella.romanelli@unifi.it


Abstract


DM232 (unifiram) and DM235 (sunifiram) are potent cognition-enhancers, which are four order of magnitude more potent than piracetam. These compounds, although not showing affinity in binding studies for the most important central receptors or channels, are able to prevent amnesia induced by modulation of several neurotransmission systems. These compounds are able to increase the release of acetylcholine from rat cerebral cortex, and, as far as unifiram is concerned, to increase the amplitude of fEPSP in rat hippocampal slices. In vitro experiments, performed on hippocampal slices, also supported the hypothesis of a role of the AMPA receptors for the cognition-enhancing properties of unifiram and sunifiram.

Prolonging EPSP at the postsynaptyc site (CA1 sites) in the hippocampus is what promotes LTM's. :D
IDRA-21:


Effect of the AMPA receptor modulator IDRA 21 on LTP in hippocampal slices.

Arai A, Guidotti A, Costa E, Lynch G.


Source

Center for the Neurobiology of Learning and Memory, University of California, Irvine 92697-3800, USA.


Abstract


IDRA 21 (7-chloro-3-methyl-3,4-dihydro-2H-1,2,4-benzothiadiazine S,S-dioxide) has been reported to modulate AMPA receptor kinetics and to improve memory in certain animal models. In the present study, its effects on synaptic transmission and long-term potentiation (LTP) were tested in hippocampal slices. IDRA 21 (500 microM) significantly increased the amplitude and halfwidth of field EPSPs. The drug did not affect monosynaptic IPSPs but enhanced disynaptically-induced feedforward IPSPs, presumably by acting on AMPA receptors on interneurons. At concentrations that facilitated synaptic transmission, IDRA 21 promoted the induction of LTP; i.e. full potentiation was obtained with stimulation paradigms that were only partially effective in the absence of drug. The results support the hypothesis that drugs which enhance AMPA receptor-mediated currents facilitate LTP.

Seemingly confirming the structural relationship between Unifiram and IDRA-21 by binding to the similar site with different affinities (IDRA-21 having a much stronger affinity).


#69 Reformed-Redan

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Posted 25 March 2013 - 12:04 AM

However, IDRA-21 is a compound to be reckoned with. It has a very long half-life and is almost as strong as seizure inducing drugs (excitability of glutamate neurons.) Thus, for this reason it has not been pushed forward but is used as a lead compound in scientific discovery of the properties of AMPA receptors.

It would be much safer and effective to decrease inhibition during the memory formation at the hippocampus(GABA sub-units in the hippocampus) rather than increase excitability of glutamate GluR1/2 metabotropic receptors. I'm not sure; but, this appears to be the nootropic activity of c16 the PKR inhibitor.

Edited by redan, 25 March 2013 - 12:08 AM.


#70 Isochroma

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Posted 25 March 2013 - 12:46 AM

7-Chloro-3-methyl-3,4-dihydro-2H-1,2,4-benzothiadiazine S,S-dioxide (IDRA 21), a congener of aniracetam, potently abates pharmacologically induced cognitive impairments in patas monkeys [Full PDF for free]

Probing the Allosteric Modulator Binding Site of GluR2 with Thiazide Derivatives

The effects of IDRA 21, a positive modulator of the AMPA receptor, on delayed matching performance by young and aged rhesus monkeys

And more!

Here's the full study in PDF format which I received directly from one of the investigators, not available to the general public:

Pharmacological Characterization of DM232 (Unifiram) and DM235 (Sunifiram), New Potent Cognition Enhancers

And more full pirated full PDFs:

Design, synthesis and preliminary pharmacological evaluation of new analogues of DM232 (unifiram) and DM235 (sunifiram) as cognition modulators.pdf

I'm going to get in big trouble for publicizing those ones...

Another full pirated PDF directly from the study's author:

Influence of ring size on the cognition-enhancing activity of DM235 and MN19, two potent nootropic drugs

And the final Master Document, direct from the study's author and not available to the general public:

Structure-activity relationship studies on unifiram (DM232) and sunifiram (DM235), two novel and potent cognition enhancing drugs

I've done awful evil by posting these so I will burn in Hell shortly - I've held the last PDF in secret for over a year.

It's time to let the carbon skeletons out of my digital closet.

Edited by Isochroma-Reborn, 25 March 2013 - 01:18 AM.


#71 Q did it!

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Posted 25 March 2013 - 01:39 AM

I have just at this moment sent a long promotional email to New Star Nootropics thanking them for stocking Sunifiram and exhorting them to stock Coluracetam and Unifiram from the Chinese manufacturers on my list, with references to the Coluracetam Experiences page I built and the threads dealing with these molecules on this forum.

I made a good business case to them.

It has been a long, hard push but I think my years of pushing are finally yielding results, with new suppliers coming online after seeing the interest and getting the connections offered by my thorough supplier research.


Many thanks for your hard work. Just ordered 1 gram of Sunifiram. A lot of people are probably going to place orders soon so i think it might make sense to start a Sunifiram Experience thread in the near future.

#72 Isochroma

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Posted 25 March 2013 - 01:43 AM

When the reports start rolling in - which I am looking forward to.

The new developments over less than the last week have dramatically upset my purchasing plans so I might be buying some Sunifiram or Coluracetam next month or as early as April 5th.

#73 alecnevsky

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Posted 25 March 2013 - 02:42 AM

I have just at this moment sent a long promotional email to New Star Nootropics thanking them for stocking Sunifiram and exhorting them to stock Coluracetam and Unifiram from the Chinese manufacturers on my list, with references to the Coluracetam Experiences page I built and the threads dealing with these molecules on this forum.

I made a good business case to them.

It has been a long, hard push but I think my years of pushing are finally yielding results, with new suppliers coming online after seeing the interest and getting the connections offered by my thorough supplier research.


Many thanks for your hard work. Just ordered 1 gram of Sunifiram. A lot of people are probably going to place orders soon so i think it might make sense to start a Sunifiram Experience thread in the near future.



Do you think you could update on Sunifiram vs Pram/Ani ? I am trying to see if Sunifiram is just a more potent piracetam or whether it has some focus/anxiolytic effects of Pram/Ani respectively.

#74 Q did it!

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Posted 25 March 2013 - 02:46 AM

I have just at this moment sent a long promotional email to New Star Nootropics thanking them for stocking Sunifiram and exhorting them to stock Coluracetam and Unifiram from the Chinese manufacturers on my list, with references to the Coluracetam Experiences page I built and the threads dealing with these molecules on this forum.

I made a good business case to them.

It has been a long, hard push but I think my years of pushing are finally yielding results, with new suppliers coming online after seeing the interest and getting the connections offered by my thorough supplier research.


Many thanks for your hard work. Just ordered 1 gram of Sunifiram. A lot of people are probably going to place orders soon so i think it might make sense to start a Sunifiram Experience thread in the near future.



Do you think you could update on Sunifiram vs Pram/Ani ? I am trying to see if Sunifiram is just a more potent piracetam or whether it has some focus/anxiolytic effects of Pram/Ani respectively.


Sure thing.

#75 Isochroma

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Posted 25 March 2013 - 02:50 AM

Yes, keep me updated too.

I also need to know whether Sunifiram is just more potent or more powerful than the racetams or other nootropics - and of course whether it has other effects unique or not - like visual color/brightness/sharpness changes, emotional/motivation, sleep/wake, etc.

Remember that potency and power usually correlate but not always.

While you wait for your Sunifiram order to arrive, if you have time please read the research paper PDFs I posted above.

If you read them you will note that Sunifiram has a very strong n-shaped dose-response curve - so overdosing might yield zero results

Doses are expected to be around 5mg for an average person, but could be anywhere from 1mg to 10mg.

Please use a 1mg-accurate digiscale and report the doses too - guessing or eyeballing such a hyperpotent molecule simply won't work.

Edited by Isochroma-Reborn, 25 March 2013 - 02:52 AM.


#76 Isochroma

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Posted 25 March 2013 - 02:55 AM

If you need a 1mg-accurate digiscale then here is the item - which is still working perfectly for me to this day after many months of use - below I quote my post from another thread:

I received my 1mg digital scale in perfect condition after 14 days in transit from the USA to Canada:




Posted Image


20g x 0.001g 1MG Digital Precision Scale HORIZON Professional Jewelry Gold Scale
$24.99 + $3.50 Shipping = $28.49 USD Total

I pulled the plastic tab off the end of one of the four included AAA cells - one of the four needed to run it (NEVER use NiMH/NiCD rechargeables for digital scales - their voltage is only 1.2V while a standard AA or AAA cell is 1.5V) popped it back in and voila, it works!

This scale represents the best value for money of any 1mg digiscale I've ever found and it ships from the USA.

For those anticipating the measure of Sunifiram, Unifiram, Coluracetam or anything needing 1mg accuracy: this is your beastie.

Edited by Isochroma-Reborn, 25 March 2013 - 03:00 AM.


#77 Q did it!

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Posted 25 March 2013 - 02:58 AM

Yes, keep me updated too.

I also need to know whether Sunifiram is just more potent or more powerful than the racetams or other nootropics - and of course whether it has other effects unique or not - like visual color/brightness/sharpness changes, emotional/motivation, sleep/wake, etc.

Remember that potency and power usually correlate but not always.

While you wait for your Sunifiram order to arrive, if you have time please read the research paper PDFs I posted above.

If you read them you will note that Sunifiram has a very strong n-shaped dose-response curve - so overdosing might yield zero results

Doses are expected to be around 5mg for an average person, but could be anywhere from 1mg to 10mg.

Please use a 1mg-accurate digiscale and report the doses too - guessing or eyeballing such a hyperpotent molecule simply won't work.


Will do and yes I do have a 1mg digiscale. You may want to start a thread, unless you are already working on one, to let the community know that Sunifiram is available and this would be a good place for people to place their experiences with the chemical.

#78 Q did it!

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Posted 25 March 2013 - 03:04 AM

Is Sunifiram water or fat soluable?

I ask this because i have always wanted to dissolve pram or ani in olive oil to see if it is better absorbed and at a lower dosage.

#79 Isochroma

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Posted 25 March 2013 - 03:07 AM

The rats/mice can't report visual effects.

The closest human-tested molecule to Sunifiram is Aniracetam - which has the pronounced visual effect of increased colour saturation.

Aniracetam is structurally similar to Sunifiram and is known to potentiate AMPA receptor-mediated neurotransmission - which is why its commercial name is Ampamet.

Therefore it's reasonable to expect increased colour saturation with Sunifiram or at least some visual changes.

Edited by Isochroma-Reborn, 25 March 2013 - 03:11 AM.

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#80 Isochroma

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Posted 25 March 2013 - 03:14 AM

Sunifiram is Soluble in water (24 mg/mL).

Edited by Isochroma-Reborn, 25 March 2013 - 03:15 AM.


#81 Q did it!

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Posted 25 March 2013 - 03:20 AM

Q did it!: Sunifiram is Soluble in water (24 mg/mL).


Thanks great to know.


The rats/mice can't report visual effects.

The closest human-tested molecule to Sunifiram is Aniracetam - which has the pronounced visual effect of increased colour saturation.

Aniracetam is structurally similar to Sunifiram and is known to potentiate AMPA receptor-mediated neurotransmission - which is why its commercial name is Ampamet.

Therefore it's reasonable to expect increased colour saturation with Sunifiram or at least some visual changes.


I had to drop Aniracetam from my stack due to it conflicting with the CILTEP stack. Hopefully Sunifiram does not do this. With Aniracetam I never really noticedincreased colour saturation just a nice stimulant affect. With coluracetam came the increased colour saturation/visual processing boost. I only take it one or twice a week at 10mg and the effects on vision do not fade over the duration of a week.

#82 megatron

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Posted 25 March 2013 - 10:56 AM

I simply can't wait to start testing Sunifiram. Massive thanks for providing those documents Isochroma-Reborn! I will thoroughly read them. Let's hope it doesn't take much more than two weeks for the drug to arrive.

#83 alecnevsky

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Posted 25 March 2013 - 04:44 PM

The rats/mice can't report visual effects.

The closest human-tested molecule to Sunifiram is Aniracetam - which has the pronounced visual effect of increased colour saturation.

Aniracetam is structurally similar to Sunifiram and is known to potentiate AMPA receptor-mediated neurotransmission - which is why its commercial name is Ampamet.

Therefore it's reasonable to expect increased colour saturation with Sunifiram or at least some visual changes.


Is this right? Majority of the studies seem to compare it to piracetam.

I certainly hope that it is.

Edit: nvm placed order will update.

Edited by alecnevsky, 25 March 2013 - 04:51 PM.


#84 Isochroma

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Posted 25 March 2013 - 06:28 PM

They compare it to PIR because PIR's the reference standard.

But structurally it's most similar to Aniracetam, and functionally too - they're both AMPAkines but PIR is not.

#85 manic_racetam

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Posted 06 April 2013 - 05:33 PM

Ampakines have been noted to impair episodic memory (http://www.nature.co...df/1301257a.pdf). I don't believe this side effect to be insuperable, provided it is a true side effect of all ampakines, but I do think it must be adequately handled.

In fact, I believe that all positive allosteric modulators of AMPA receptors induce a depletion of glutamate, and potentially of other substrates, as well as of ions. Glutaminergic depletion may manifest itself via symptoms of fatigue, brain fog, or drowsiness. I believe ampakines do improve most forms of learning and memory, provided they are used in moderation and in conjunction with appropriate forms of glutamate and ions.


Excuse my lack of knowledge on this subject, but could the episodic memory impairment be due to excitotoxicity of immature oligodendrocytes?

From http://www.ampakines.org/chemistry.htm "Prolonged activation of their AMPA-GluR causes Ca2+ overload, resulting in excitotoxic death. Oligodendroglial progenitors and immature oligodendrocytes are susceptible to excitotoxicity, whereas mature oligodendrocytes are resistant."

Furthermore, would sunifiram even cause this based on it's low toxicology profile?
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#86 Isochroma

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Posted 06 April 2013 - 08:05 PM

Sunifiram has been found to be non-toxic in experimental animals:

From AMPA-receptor activation is involved in the antiamnesic effect of DM 232 (unifiram) and DM 235 (sunifiram):

"It should be noted that deleterious behavioural effects were not present at doses 100-fold higher than the active ones indicating that these compounds are endowed with an extremely low toxicity."


From DM235 (sunifiram) - a novel nootropic with potential as a cognitive enhancer:

"DM235 is, in fact, endowed with the main pharmacological properties of piracetam-like compounds: facilitation of memory processes, lack of toxicity and side effects and a lack of affinity towards the most important central receptors."


My brain says it's ok too!

So please enjoy riding the Sunny-Train - the fare's cheap and the sights are magnificent.

Edited by Isochroma-Reborn, 06 April 2013 - 08:12 PM.

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#87 Reformed-Redan

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Posted 07 April 2013 - 06:06 AM

Can we get a group buy going for IDRA-21. This stuffs just too amazing.

#88 zeroskater6979

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Posted 07 April 2013 - 12:18 PM

What's the cost?

#89 Izan

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Posted 07 April 2013 - 01:54 PM

Can we get a group buy going for IDRA-21. This stuffs just too amazing.

i can't seem to find much information about this ampakine. what does it do?

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#90 ihsanozkan

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Posted 08 April 2013 - 08:41 AM

Hi there, I am new to forum, and ordered Sunifiram after reading this post and before becoming member. I am waiting for my Sunifiram to arrive, I did not try it yet.

Also I would like to participate group buy of IDRA-21 , Coluracetam and Unifiram.






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