110 replies to this topic

[Ampa-omega]

sunifiram is supposedly low toxicity and could be since its potent at low doses,
mouse study obviously, i don't know of any human study,maybe just cant find it. and I'm not sure why maybe they just focused on transitioning to the other ampakines.

There are no official human studies with sunifiram administration. But there are few people who tested it on themselves, including me I plan to make compilation on its effects in near future.

alright well please remember to post your experience for us! I'm pretty interested. How safe do you feel it is? any negative responses? and if you have seen any papers that we probably haven't seen on sunifiram, please post.

Edited by Ampa-omega, 09 February 2012 - 04:48 PM.

[Googoltarian]

"How safe do you feel it is? any negative responses?"

I myself did not felt any negative effects. One test subject experienced headache.

[LazarusMan]

Found this today while browsing the interwebs: http://www.fas.org/i...jason/human.pdf
DARPA/DOD report on performance enhancement of sleep deprived soldiers. Ampakines are mentioned on pag 51 and on. I wasn't sure if anyone had read this already so if not, enjoy.

[zeroskater6979]

Found this today while browsing the interwebs: http://www.fas.org/i...jason/human.pdf
DARPA/DOD report on performance enhancement of sleep deprived soldiers. Ampakines are mentioned on pag 51 and on. I wasn't sure if anyone had read this already so if not, enjoy.

yeah, apparently it didnt work very well for simulated night shift work, but did work for plain sleep deprivation, not sure why one and not the other. that was for cx717 i believe, but i still think it would significantly boost intelligence in healthy people in normal alert conditions. cx1739 is about 5 times more potent and just as safe, can't imagine how much smarter you would be if you had access to it. hmm i guess i need it to aid my imagination . i think they need to conduct a clinical trial on healthy individuals to assess the cognitive effects, but focusing on higher level thinking, thats where it gets interesting. nobody cares if cx516 can help you remember the positions of playing cards.

[Ampa-omega]

I'm pretty sure this relates to the topic
http://www.longecity...da-enhancement/

Edited by Ampa-omega, 10 February 2012 - 08:55 PM.

[Ampa-omega]

If you haven't seen this, this pretty much indicates that pramiracetam is definitely an ampakine.
Since pramiracetam has strong effects on nitric oxide.
http://www.longecity...6-pramiracetam/
http://www.longecity...am-experiences/

http://www.reddit.co...kines_possible/

The biarylpropylsulfonamide class of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) potentiators represented by N-2-(4-(4-cyanophenol)phenol)propyl-2-propanesulfonamide (LY404187) and ®-4′-[1-fluoro-1-methyl-2-(propane-2-sulfonylamino)-ethyl]-biphenyl-4-carboxylic acid methylamide (LY503430) are positive, allosteric AMPA receptor activators, which enhance AMPA receptor-mediated neurotransmission by reducing desensitization of the ion channel. Although these compounds have efficacy in in vivo rodent models of cognition, depression, and Parkinson's disease, little is known about biochemical pathways activated by these agents. Given the well established regulation of the nitric oxide/cGMP pathway by excitatory neurotransmission, the current study characterized AMPA receptor potentiator-mediated cGMP response in mouse cerebellum. Acute treatment by both LY404187 and LY503430 [2.0, 5.0, or 10 mg/kg subcutaneously (s.c.)] elevated basal cerebellar cGMP levels in a dose-dependent manner.

activation of AMPA receptors induces cGMP levels. pretreatment with the N-methyl-D-aspartate (NMDA) open channel blocker dizocilpine (0.3 and 1.0 mg/kg i.p.) also abolished the AMPA receptor potentiator-mediated cGMP accumulation, indicating that activation of AMPA receptors leads to NMDA receptor-mediated transmission involved in cGMP regulation.

Definitely will be interesting to see how scientist take advantage of this information and fine tune the cGMP/cAMP system, relates to the pde4 inhibiton/Chemically induced LTP thread we have.
http://www.longecity...ly-induced-ltp/

on a related note: pde9 inhibition

The PDE9A enzyme is expressed primarily in the brain, with high concentrations in the cerebellum, neocortex, striatum, and hippocampus, and acts to limit the cGMP-mediated signal transduction which occurs following glutamate binding to NMDA receptors. Consequently selective PDE9A inhibitors were predicted to prolong intracellular responses to glutamate and enhance glutamate signalling, and since this process is known to be involved in learning and memory, PDE9A inhibitors should have a nootropic effect and may be useful in the treatment of Alzheimer's.[1]

http://en.wikipedia....iki/BAY_73-6691

Edited by Ampa-omega, 13 February 2012 - 05:47 PM.

[zeroskater6979]

pram just made me super tired. i recommend it if you like day-time naps. whereas cx ampakines induce wakefulness and all around cognitive ass-kickery.

[Ampa-omega]

pram just made me super tired. i recommend it if you like day-time naps. whereas cx ampakines induce wakefulness and all around cognitive ass-kickery.

Ya, i heard that quite a lot from some racetam users, dont know why that is. Heard that response from Aniracetam users as well. Would be cool to figure out what is going on that makes people sleepy/tired. try them with some caffiene.


this is interesting, maybe adenosine is effected by cGMP increases:

Adenosine A3 receptors regulate serotonin transport via nitric oxide and cGMP.

Many antidepressants inhibit 5-hydroxytryptamine (5HT) transport resulting in increased 5HT levels in the synapse. However, physiological regulation of neurotransmitter uptake has not been demonstrated. We have examined the effect of receptor-activated second messengers on the 5HT transporter in rat basophilic leukemia cells (RBL 2H3). Here, we show that activation of an A3 adenosine receptor results in an increase of 5HT uptake in RBL cells, due to an increase in maximum velocity (Vmax). The A3 adenosine receptor-stimulated increase in transport is blocked by inhibitors of nitric oxide synthase and by a cGMP-dependent kinase inhibitor. In fact, compounds that generate nitric oxide (NO) and the cGMP analog 8-bromo-cGMP mimicked the effect of A3 receptor stimulation, suggesting that the elevation in transport occurs through the generation of the gaseous second messenger NO and a subsequent elevation in cGMP. Additionally, the 5HT transporter is differentially regulated by second messengers since direct activation of protein kinase C by phorbol esters decreases 5HT uptake by decreasing Vmax. Our results suggest that the changes in transport are due to a direct modification of the 5HT transporter, possibly by phosphorylation, which appears to alter the rate at which transport occurs. As the 5HT transporter in RBL cells is identical to that in neurons, our results suggest that analogous mechanisms may operate in the brain.

Edited by Ampa-omega, 13 February 2012 - 06:22 PM.

[LazarusMan]

Ya, i heard that quite a lot from some racetam users, dont know why that is. Heard that response from Aniracetam users as well. Would be cool to figure out what is going on that makes people sleepy/tired. try them with some caffiene.

I get the drowsy effect from aniracetam but not oxiracetam. I was guessing it had something to do with aniracetam's effects on the 5HT-2a receptors. I haven't really tried more than 150mg of prim so the verdict is still out on that one for me.

[Ampa-omega]

Ya, i heard that quite a lot from some racetam users, dont know why that is. Heard that response from Aniracetam users as well. Would be cool to figure out what is going on that makes people sleepy/tired. try them with some caffiene.

I get the drowsy effect from aniracetam but not oxiracetam. I was guessing it had something to do with aniracetam's effects on the 5HT-2a receptors. I haven't really tried more than 150mg of prim so the verdict is still out on that one for me.

Oxiracetam supposedly metabolizes into a GHB receptor agonist prodrug, now i dont know enough on GHB receptor pharmacology to tell you if Oxiracetam will make you fall asleep or make you stimulated, but this is what i heard.

Oxiracetam's structure suggests it is at least partially metabolized to GABOB. GABOB is a GHB agonist and agonism at the GHB receptor produces stimulatory effects last I heard. Incidentally, with respect to GABOB, I am aware it is available as a dietary supplement; however, I rather highly doubt that it crosses the blood-brain barrier due to its polarity. Oxiracetam looks like a reasonable prodrug with a much better chance of crossing the BBB. Selective γ-hydroxybutyric acid receptor ligands increase extracellular glutamate in the hippocampus, but fail to activate G protein and to produce the sedative/hypnotic effect of γ-hydroxybutyric acid

Oxiracetam does act to modulate NMDA receptors. So both of those mechanisms could work together to compound a stimulatory effect.

Edited by Ampa-omega, 13 February 2012 - 06:49 PM.

[zeroskater6979]

i know this is a novice question but im still curious. Amap-omega i know you probably know the answer to this question. how is it that ampakines do not cause excitotoxicity seeming as glutamate is usually the culprit? i know it has something to do with it being a positive allosteric modulator and not an agonist but isn't there still the possibility of it being dangerous?

[Ampa-omega]

i know this is a novice question but im still curious. Amap-omega i know you probably know the answer to this question. how is it that ampakines do not cause excitotoxicity seeming as glutamate is usually the culprit? i know it has something to do with it being a positive allosteric modulator and not an agonist but isn't there still the possibility of it being dangerous?

yes there is potential but it depends on the flow of ions into the cell. depends on the compound, allosteric modulators bind at a seperate site than the neurotransmitter agonist. too much activation, and too many uncontrolled ions flow into the cell and damage will happen. Most allosteric modulators have good safety profiles but some can potentiate excitotoxicity, its the direct agonist which can be toxic, receptor modulators can potentiate them, so there is a concern for toxicity.

http://www.bluelight...-excitotoxicity
http://www.bluelight...logy-discussion
http://www.mindandmu...acetam-part-ii/

Edited by Ampa-omega, 13 February 2012 - 09:19 PM.

[Ampa-omega]

http://www.sumanasin.../receptors.html

[Ampa-omega]

piracetam and oxiracetam both enhance theta brain currents, so that could cause sleepiness.
http://www.longecity...m-vs-piracetam/
http://content.karge....asp?Doi=118161

[zeroskater6979]

i think cx717 or cx1739 or the high impact ampakines will be the first drug(s) to mimic the effects of NZT-48. then we'll use the ampakines to increase our intelligence so we can discover drugs than enhance our intelligence more so. im pretty sure those workin down at cortex have tried an ampakine at least one time despite the ethical concerns. i mean who wouldn't? they know what they're doing and the impact their research is going to have.

[Ampa-omega]

i think cx717 or cx1739 or the high impact ampakines will be the first drug(s) to mimic the effects of NZT-48. then we'll use the ampakines to increase our intelligence so we can discover drugs than enhance our intelligence more so. im pretty sure those workin down at cortex have tried an ampakine at least one time despite the ethical concerns. i mean who wouldn't? they know what they're doing and the impact their research is going to have.

I dont think a NZT will happen until you understand the brain in a more whole matter especially ion channels, excitatory neurotransmission and the inhibition of it, signal transduction and all the specific kinases, it will require a whole level of understanding. ampakines will help to make your glutamate receptors more excitable and prevent their deactivation but its still nothing like a hypothetical NZT which will probably require incorporating every neurotransmitter system and likely understanding the glial cells. Plus you have to understand the different brain regions and the functions they control.

Edited by Ampa-omega, 24 February 2012 - 12:49 AM.

[zeroskater6979]

of course it wont be as astounding as nzt, as you said a drug would have to act on multiple neurotransmitter systems synergistically. nzt affects so many psychological variables in addition to cognition. however some high impact ampakines have been implicated to treat depression, which suggests that they improve mood (as did nzt) and intelligence. so even though they act only through ampa mediated glutamatergic pathways (increasing BDNF in this instance) it could affect several psychological measures as well as intelligence. sounds close enough to me. you may not learn a language in three days but im sure it would a hell of a lot easier.

[gamesguru]

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.

Edited by dasheenster, 23 March 2012 - 03:16 PM.

[zeroskater6979]

farampator is the only ampakine that has demonstrated deleterious effects on episodic memory. there haven't been any studies that i know of that suggest ampakines cause glutamate depletion and thus the side-effects you listed. the most severe SE's reported have been headache and nausea and only at maximum tolerated doses.

[Nattzor]

Is it possible for you to update more about your trials Googoltarian?
Thanks!

[Isochroma]

I have six Chinese suppliers of Sunifiram [in stock!] with prices of: $88, $100, $115, $120, $130, $200 per gram including EMS fee to my door.

I will likely be buying 1g in early January 2012.

Dose is 5mg for a 150lb person so 1g = 200 doses.

Sunifiram is actually 1000x more potent than Piracetam, while Noopept is only 100x more potent.

Edited by Isochroma-Reborn, 30 November 2012 - 12:13 AM.

[zeroskater6979]

Good luck Isochroma, can't wait to hear your experiences.

[SuperjackDid_]

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.

additional supplement l-glutamic is the key to deal with depletion of glutamate?

[Isochroma]

GLUtamate! It might be true.

This is day 18 on PIR + MSG and the combo seems to be working like a perfect charm.

The long focus on the Acetylcholinergic system in relation to both racetams and ampakines has, I believe been detrimental to the further development of Glutamatergic theories of operation.

[dami79]

What interests me: how ampakines influence lucid dreaming?

[Isochroma]

Aniracetam made it harder for me to remember my dreams.

[#1stunna]

bump, ampakines seem to be the future

[zeroskater6979]

no they don't. pharma companies aren't interested anymore. there are other routes being taken though

[Heh]

Like what? Neuropeptides?

[maxwatt]

Aniracetam made it harder for me to remember my dreams.

More likely due to a change in sleep patterns than a direct effect on memory per se.

Dreams are remembered when one awakens during or shortly after a REM sleep cycle. It is possible if one is sleeping less, falling asleep later than usual, (but awakening at the same time as before) that the REM sleep cycle no longer coincides with the awakening time. You could try setting your alarm earlier or later than usual to try and catch your dreams. Most people's sleep cycle is 1.5 hours, so you can calculate how much to offset your waking time to have the same number of sleep cycles, or fractional sleep cycle, to "hit the dream spot." I am curious how this might work for you.