37 replies to this topic

[Reformed-Redan]

I was doing some research on alpha 7 nicotinic receptors. I found that nefiracetam is a seriously underrated nootropic. I remember hearing about how it shrinks balls or something to that matter. Well take a look at these results. I haven't seen an other racetam apart from IDRA-21 with such strong nootropic qualities.

Nefiracetam, a nootropic agent, enhanced the slope of field excitatory postsynaptic potentials in the CA1 region of rat hippocampal slices to about 170% of basal levels, being evident still at 4-h washing-out of the drug. A similar sustained enhancement (≥16 h after i.m. injection with nefiracetam) was observed in the population spikes recorded from the granular cell layer of the intact mouse hippocampus. Saturation of the enhancement in the synaptic strength occluded potentiation obtained with long-term potentiation (LTP) induced by high-frequency (tetanic) stimulation, and vice versa. Interestingly, the facilitatory action of nefiracetam was blocked by either the nicotinic acetylcholine (ACh) receptor antagonists, α-bungarotoxin and mecamylamine, or the selective protein kinase C (PKC) inhibitor, GF109203X, but in contrast, it was not affected by d-2-amino-5-phosphonovaleric acid (APV), a selective N-methyl-d-aspartate (NMDA) receptor antagonist. The results of the present study suggest that nefiracetam, whereas the action is independent of NMDA receptors, induces an `LTP-like' facilitation of hippocampal synaptic transmission as a consequence of modulation of nicotinic ACh receptors and PKC. This may represent a likely mechanism underlying the cognition-enhancing actions of nefiracetam.

http://www.sciencedi...9399013128?np=y

and

The present study was designed to assess whether the facilitatory action of nefiracetam, a pyrrolidone derivative, on hippocampal postsynaptic responses is dependent upon N-methyl-d-aspartate (NMDA) receptors or not, by monitoring population spikes (PSs) in the dentate gyrus of hippocampal slices from mice lacking the NMDA receptor ϵ1 subunit. Nefiracetam (1 μM) induced a sustained facilitation of postsynaptic responses in the dentate gyrus of hippocampal slices from wild-type mice. The facilitation occluded the potentiation induced by high-frequency stimulation at the perforant path, and vice versa, suggesting a common mechanism between them. The perforant path long-term potentiation (LTP) was not induced in ϵ1 subunit knock-out mice, but nefiracetam (1 μM) persistently potentiated PS amplitude, reaching 280% of basal levels 50 min after 10-min treatment, similar to the potentiation achieved with wild-type mice. The results of the present study, thus, suggest that nefiracetam exerts its facilitatory action on hippocampal postsynaptic responses in an NMDA receptor-independent manner.

http://www.sciencedi...9302035564?np=y

Edited by yadayada, 28 April 2013 - 06:07 AM.

[Darkat]

I've always held that nefiracetam is underrated - it is the only racetam that I have used that has sustained results - everything else: oxi, ani, prami, piracetam seem to dwindle in their results after a few days to a week or two. I have even found the same tolerance effect with noopept and sunifiram. Nefi is the only one with consistant results.

It would be nice to see further trials on it with regard to the possible side effects. Most research so far tends to point to the testicular/kidney/bladder problems in dogs and rats only, there is no evidence of damage in primates or humans. There is another trial going on in Australia, that is supposed to report later this year - hopefully this will shed more light on any side effects. In the mean time, I continue to use it at no more than 200mg per day and taking regular breaks.

[Reformed-Redan]

I've always held that nefiracetam is underrated - it is the only racetam that I have used that has sustained results - everything else: oxi, ani, prami, piracetam seem to dwindle in their results after a few days to a week or two. I have even found the same tolerance effect with noopept and sunifiram. Nefi is the only one with consistant results.

It would be nice to see further trials on it with regard to the possible side effects. Most research so far tends to point to the testicular/kidney/bladder problems in dogs and rats only, there is no evidence of damage in primates or humans. There is another trial going on in Australia, that is supposed to report later this year - hopefully this will shed more light on any side effects. In the mean time, I continue to use it at no more than 200mg per day and taking regular breaks.

There's a decent thread here, http://www.longecity...am/page__st__60.
Everyone got all hyped about loosing they're testicles or whatnot. Dunno. Do you get any side effects? Headache irritability feeling emotionally "numb"?

[Darkat]

No, never noticed any side effects - although I have not gone as far as having testosterone levels checked - but have not noted any reduction in libido.. I find that nefiracetam gives me a "calm focus" - really noticeable anxiolitic effect with a definite boost to focus on anything that you are doing.
I generally use for 5 days, then take the wekends off it. This way you don't notice any effect from stopping using it. I have also taken 3 breaks of around 7 days from it over the last 3 months. After 3 to 4 days you can definitely tell that the calming effect has worn off. So, basically, I have used it 5 days per week for 3 weeks and then 1 week off, for the last 3 months. Only positive effects from it's use - no numbness, irritability or headaches (although I do take choline daily).

Edited by Darkat, 28 April 2013 - 09:21 AM.

[peakplasma]

It is a very interesting racetam but as ScienceGuy pointed out it is a GABA-A agonist which can sometimes be problematic. I think occasional use would be perfect.

[medievil]

It is a very interesting racetam but as ScienceGuy pointed out it is a GABA-A agonist which can sometimes be problematic. I think occasional use would be perfect.

I disagree, i dont see how that would be problematic? if thats the case endogenious gaba would be a problem, issues with benzo's do not relate AT ALL to other gaba agonists as anecdotes on herbs etc allready have been proving for century's.

As to the topic, agree by far.

http://noveltreatmen.../?view=flipcard

More info on my blog.

[dreth7]

It is a very interesting racetam but as ScienceGuy pointed out it is a GABA-A agonist which can sometimes be problematic. I think occasional use would be perfect.

I disagree, i dont see how that would be problematic? if thats the case endogenious gaba would be a problem, issues with benzo's do not relate AT ALL to other gaba agonists as anecdotes on herbs etc allready have been proving for century's.

As to the topic, agree by far.

http://noveltreatmen.../?view=flipcard

More info on my blog.

Nice blog by the way!

I cant remember medievil have you dabbled withe nefi in the past?

Edited by dreth7, 30 April 2013 - 08:36 PM.

[medievil]

Yes, it allways completely reversed psychosis induced by stims nothing else can do that, it was mind blowing, i wanted to contact the company that patented it to market it for shizo but they never replied.

[peakplasma]

Yes, it allways completely reversed psychosis induced by stims nothing else can do that, it was mind blowing, i wanted to contact the company that patented it to market it for shizo but they never replied.

Very interesting.. any other nootropics come close to this?

[medievil]

nothing ever did that mate and i tried everything.

Serieusly, the combo of nefiracetam and amphetamine i feel would pretty much the closest to the golden bullet for shizophrenia.

[peakplasma]

nothing ever did that mate and i tried everything.

Serieusly, the combo of nefiracetam and amphetamine i feel would pretty much the closest to the golden bullet for shizophrenia.

Your blog is really cool. Do you have a hypothesis on which mechanism is responsible for this?

Also, have you tried Sunifiram yet? In the 2013 paper it discusses that it also acts via CaM kinase II and PKC. It stimulates the glycine-binding site although, not clear if action is analogous to nefiracetam.

Also, what is the state of Nefiracetam research? Has it progressed to human trials? Nevermind, it seems I'm really ignorant on nefiracetam.. I'm going to do some research now.

Edited by peakplasma, 30 April 2013 - 09:57 PM.

[medievil]

no i havent my ADD owns me i could work on my blog, study, start a shop but instead nearly end homeless, dont have money to try anything anymore.

Yes its glutaminergic effects.

[Reformed-Redan]

I hope Isochroma-reborn has some more suppliers for Nefiracetam on his list. Anyone planning on placing an order from sunnootropics?

[peakplasma]

I hope Isochroma-reborn has some more suppliers for Nefiracetam on his list. Anyone planning on placing an order from sunnootropics?

Go halves?

[Reformed-Redan]

I hope Isochroma-reborn has some more suppliers for Nefiracetam on his list. Anyone planning on placing an order from sunnootropics?

Go halves?

Yeah

[dreth7]

Bummer they only sell in 100g amounts. I was hoping to trial some over summer with intensive classes.

[Reformed-Redan]

Bummer they only sell in 100g amounts. I was hoping to trial some over summer with intensive classes.

They sell much more than that. Click on the dropdown menu of the amount. It goes up to 5kg.

[dreth7]

Bummer they only sell in 100g amounts. I was hoping to trial some over summer with intensive classes.

They sell much more than that. Click on the dropdown menu of the amount. It goes up to 5kg.

No I meant that in quite the opposite sense. As in, I wish they sold smaller amounts to trial out before I purchased 100g of something with a daily dosage in the miligram range.

[Darkat]

Bummer they only sell in 100g amounts. I was hoping to trial some over summer with intensive classes.

They sell much more than that. Click on the dropdown menu of the amount. It goes up to 5kg.

No I meant that in quite the opposite sense. As in, I wish they sold smaller amounts to trial out before I purchased 100g of something with a daily dosage in the miligram range.

Try vantagecc on ebay - sells it in 5g up to 100g amounts.

[dreth7]

Just ordered some nefiracetam.

Has anyone else seen the study citing piracetam reduces the density of alpha 7 nicotinic receptors? I swear I saw that somewhere on these forums a day ago.

[Reformed-Redan]

Just ordered some nefiracetam.

Has anyone else seen the study citing piracetam reduces the density of alpha 7 nicotinic receptors? I swear I saw that somewhere on these forums a day ago.

Here you go:

[Effects of piracetam and meclofenoxate on the brain NMDA and nicotinic receptors in mice with different exploratory efficacy in the cross maze test].

[Article in Russian]
Kovalev GI, Firstova IuIu, Salimov RM.

Abstract


A population of outbred mice of the ICR strain was divided into two subpopulations according to their high (EH mice) or low (EL mice) exploratory efficacy in the closed cross maze test. In addition, the EH and EL mice differed in the number of binding sites of (i) [G-3H]-MK-801 with NMDA receptors from hippocampus and (ii) [G-3H]-nicotine with nicotine cholinoreceptors (nACh) from neocortex. A subchronic administration of the cognition enhancer piracetam (200 mg/kg, once per day for 5 days) increased by 70% the number of binding sites of NMDA receptors in the EL mice. At the same time, this treatment decreased the density of neocortical nACh receptors in both EL and EH mice (by 55% and 40%, respectively). A subchronic administration of the cognition enhancer and anti-oxidant meclofenoxate (100 mg/kg, once per day for 5 days) also decreased the density of neocortical nACh receptors in both EL and EH mice (by 48% and 20%, respectively). However, meclofenoxate also increased by 41% the number of binding sites of NMDA receptors in the EH mice.

Lol, the effects of piracetam have still yet to be fully elucidated. And people are taking Sunifiram in large quantities. We must be crazy to take NSI-189 and PRL-8-53, least speakof IDRA-21.

[dreth7]

Just ordered some nefiracetam.

Has anyone else seen the study citing piracetam reduces the density of alpha 7 nicotinic receptors? I swear I saw that somewhere on these forums a day ago.

Here you go:

[Effects of piracetam and meclofenoxate on the brain NMDA and nicotinic receptors in mice with different exploratory efficacy in the cross maze test].

[Article in Russian]
Kovalev GI, Firstova IuIu, Salimov RM.

Abstract


A population of outbred mice of the ICR strain was divided into two subpopulations according to their high (EH mice) or low (EL mice) exploratory efficacy in the closed cross maze test. In addition, the EH and EL mice differed in the number of binding sites of (i) [G-3H]-MK-801 with NMDA receptors from hippocampus and (ii) [G-3H]-nicotine with nicotine cholinoreceptors (nACh) from neocortex. A subchronic administration of the cognition enhancer piracetam (200 mg/kg, once per day for 5 days) increased by 70% the number of binding sites of NMDA receptors in the EL mice. At the same time, this treatment decreased the density of neocortical nACh receptors in both EL and EH mice (by 55% and 40%, respectively). A subchronic administration of the cognition enhancer and anti-oxidant meclofenoxate (100 mg/kg, once per day for 5 days) also decreased the density of neocortical nACh receptors in both EL and EH mice (by 48% and 20%, respectively). However, meclofenoxate also increased by 41% the number of binding sites of NMDA receptors in the EH mice.

Lol, the effects of piracetam have still yet to be fully elucidated. And people are taking Sunifiram in large quantities. We must be crazy to take NSI-189 and PRL-8-53, least speakof IDRA-21.

I second that notion. The more I use "nootropics" and research, the more irresponsible I ultimately end up feeling.

Based off of that study though, wouldn't the reduction of alpha 7 nicotinic receptors simply be a homeostatic counter measure induced by the increase in NMDA receptors. That is, wouldn't there be a lesser need of the long term synaptic changes induced by the nicotinic receptors if plasticity was already being affected from the front end by increased activity of NMDARs?

[Reformed-Redan]

Just ordered some nefiracetam.

Has anyone else seen the study citing piracetam reduces the density of alpha 7 nicotinic receptors? I swear I saw that somewhere on these forums a day ago.

Here you go:

[Effects of piracetam and meclofenoxate on the brain NMDA and nicotinic receptors in mice with different exploratory efficacy in the cross maze test].

[Article in Russian]
Kovalev GI, Firstova IuIu, Salimov RM.

Abstract


A population of outbred mice of the ICR strain was divided into two subpopulations according to their high (EH mice) or low (EL mice) exploratory efficacy in the closed cross maze test. In addition, the EH and EL mice differed in the number of binding sites of (i) [G-3H]-MK-801 with NMDA receptors from hippocampus and (ii) [G-3H]-nicotine with nicotine cholinoreceptors (nACh) from neocortex. A subchronic administration of the cognition enhancer piracetam (200 mg/kg, once per day for 5 days) increased by 70% the number of binding sites of NMDA receptors in the EL mice. At the same time, this treatment decreased the density of neocortical nACh receptors in both EL and EH mice (by 55% and 40%, respectively). A subchronic administration of the cognition enhancer and anti-oxidant meclofenoxate (100 mg/kg, once per day for 5 days) also decreased the density of neocortical nACh receptors in both EL and EH mice (by 48% and 20%, respectively). However, meclofenoxate also increased by 41% the number of binding sites of NMDA receptors in the EH mice.

Lol, the effects of piracetam have still yet to be fully elucidated. And people are taking Sunifiram in large quantities. We must be crazy to take NSI-189 and PRL-8-53, least speakof IDRA-21.

I second that notion. The more I use "nootropics" and research, the more irresponsible I ultimately end up feeling.

Based off of that study though, wouldn't the reduction of alpha 7 nicotinic receptors simply be a homeostatic counter measure induced by the increase in NMDA receptors. That is, wouldn't there be a lesser need of the long term synaptic changes induced by the nicotinic receptors if plasticity was already being affected from the front end by increased activity of NMDARs?

I don't know. The more I read about these compounds the more I realize I don't know.

[SnowFlake]

Bummer they only sell in 100g amounts. I was hoping to trial some over summer with intensive classes.

I usually don't like to mention vendors unless it's an review thread concerning vendors, but I picked my 25 grams from the relatively reputable ebay vendor called Vantagecc. The product is extremely pure. I have tried Nefi in the dose range of anything from 150mg to a little over 700mg. Too much makes you really drowsy and sleepy. I found my sweet spot to be at somewhere in the 250-350 mg range.

[dreth7]

Bummer they only sell in 100g amounts. I was hoping to trial some over summer with intensive classes.

I usually don't like to mention vendors unless it's an review thread concerning vendors, but I picked my 25 grams from the relatively reputable ebay vendor called Vantagecc. The product is extremely pure. I have tried Nefi in the dose range of anything from 150mg to a little over 700mg. Too much makes you really drowsy and sleepy. I found my sweet spot to be at somewhere in the 250-350 mg range.

How would you describe that sweet spot?

[Reformed-Redan]

Well, I just dosed around 200mg in the morning. Subjectively, I felt a strong... umm... *aha* like feeling. Like I was brushing my teeth and usually wet my toothbruth when putting toothpaste on it; but, this time I forgot or just didn't or thought I did; but, didn't. I immediately noticed that the toothbrush was dry with the toothpaste on it when I started brushing my teeth and thought, *oh, this is good because I get a better brushing of teeth because the toothpaste sticks to my teeth rather than just foaming up when the toothbrush is wet.* Lol. don't know, so far so good.

Edited by yadayada, 09 May 2013 - 05:39 PM.

[Reformed-Redan]

I think the best way to describe nefiracetam's effects would be on the wavelength of *more coherent thinking.*

[golden1]

*oh, this is good because I get a better brushing of teeth because the toothpaste sticks to my teeth rather than just foaming up when the toothbrush is wet.*

woah mind-blown.

[Reformed-Redan]

*oh, this is good because I get a better brushing of teeth because the toothpaste sticks to my teeth rather than just foaming up when the toothbrush is wet.*

woah mind-blown.

I know right? I'd say it feels a little like nicotine. Might have to see how the two synergize.

[mait]

All in all the testicular toxicity concerns are the only rat and dog spices specific???