659 replies to this topic

[Reformed-Redan]

I am not able to procure this compound at this time. I do not know when I could get this compound. Sorry guys.

[Jul89]

You could get it from teamtlr.com 

Still needs to be checked if it is really what you want and halfway safe.

[Forty Six & 2]

This synthesis is extraordinarily difficult.  To be straight, I knew there was no way it was going to be produced by any other parties, or would have been quite surprised to see such (and no way at said cost basis reported).  

It has been a challenge far beyond what was even already anticipated to be highly difficult, however, we are doing last purifications and should have the NRX-1074 in hand soon aliquoted in 50mg sterile vials.

 

Notably, we got crushed on the yield relative to what is anticipated, so we are basically not making anything at current pricing. 

 

This batch coming is just covering present pre-orders.  We are in process with a second batch as well, which should be ready in 3-5 weeks.

This second and final batch is as well limited, so when it is gone, it is gone.  Much of this batch is already reserved via pre-orders and it is limited as to what is still available.

 

Within our research with the small amount of material we pulled before final purifications, we have seen solid efficacy in animal model research.

While nothing can be construed as undeniable 100% safe, all signs point to it being a highly efficacious and safe agent.

 

For those who wish for an alternative that is oral administered and less costly to perform appropriate research and acts via the same pathway with similar efficacy, we as well have seen stellar results with our GLYX-OX matrix, even exceeding high expectations.

One may as well wish to combine the two agents, therein being able to use lower doses of each.  Further, a low dose os our SNRB-OX further potentiates the efficacy.

 

Best of Success to all who engage progressive research in this area. 

 

[nyckrazy]

im am very interested in nrx! wouls join a group buy in a heart beat.

[uppercut1991]

Guys what about glyx-13, maybe that would be easier to synthesis. I dont mind shooting it intravenously. What do you think? 

[nyckrazy]

You dont mind shooting up? you must be a pro.

[Milkyway11]

So is TLR not going to continuously stock NRX 1074?  If not then I would like to participate in a group buy.

[uppercut1991]

,, The effect of a single dose of GLYX-13 was nearly twice as great as the effect seen in clinical trials of most conventional antidepressants after 4–6 weeks of treatment.'' Hope we will be able to obtain this molecule soon.

 

[Jul89]

it does sound very promising

[opusensemble]

I have recently placed a post, while looking for an alleged "Ketamine cousin" from nature from a 2013 research from South Korea: 

http://www.longecity...on/#entry765325
 

Radix Polygalae

Preclinical evidence of rapid-onset antidepressant-like effect in Radix Polygalae extract. (2014 study)
http://www.ncbi.nlm....pubmed/24520403
http://journals.plos...al.pone.0088617

 

At least that research paper concludes on Radix Polygalae, the root from polygala tenuifolia (a.k.a. yuan zhi -> Chinese: 遠志), the following: 

 

"RP may possibly substitute for other rapid-onset antidepressants like ketamine that are associated with addiction risk and unacceptable side effects. It will be worthy to further evaluate the pharmacologic effects of RP and especially its constituent parts as candidates for novel antidepressant development."

As counter-argument: There is actually a study on the same herb identifying 6 saponin molecules (YuanZhi-1 to YuanZhi-6, 4 of them with antidepressant potential)
http://www.sciencedi...278584614000438
http://sci-hub.io/10...880200903280034
Being hormones, is not very attractive due to the problems they can induce in hormonal systems. Also, they are shown in the study to have anti-depressive potential through affinity to monoamines (SERT, DAT, NET), which gets it on the same realm as SSRIs/SNRIs and TCAs. So, RP gets a bit discouraging there, despite other article from 2015 mentioning the potential of saponins in addressing depression: 

Saponins: the phytochemical with an emerging potential for curing clinical depression. (<- the word "curing" was probably used irresponsibly or lost in translation)

http://www.ncbi.nlm....pubmed/25075957

http://sci-hub.io/10...419.2014.942661

What I wonder is how (in that first 2013 research paper) could 1x (0.1 mg/kg; p.o.) have the same effect in mice as 1x ketamine (10 mg/kg; i.p.), after 30 minutes. It was a 100x smaller dosage !!! 

The study details the extraction method: 

 

"Preparation of Radix Polygalae extract The dried RP samples were immersed in 70% ethanol and boiled at 80uC for 1 hour. The extract was collected and the procedure repeated once more (80uC reflux for 40 min), after which the combined filtrate was evaporated on a rotary evaporator under reduced pressure and freeze-dried to yield about 28% (w/w) of the extract. Supporting information is available for the HPLC quantification of key molecules (Figure S1). For experimental use, crude extracts were completely dissolved in distilled water."

One would be led to think hat any extract would do. The thing is, another study on the same root administered to mice by gastric intubation during 28 days, used dosages of about 280mg/Kg/day. 

The preparation of the extracts doesn't seem much different in the sense that it doesn't seem to allow isolating any of the constituent parts of the root. 

Antidepressant effects of the extract YZ-50 from Polygala tenuifolia in chronic mild stress treated rats and its possible mechanisms.
http://www.ncbi.nlm....pubmed/20645779
http://moscow.sci-hu...6ef2/hu2010.pdf
 

"The air-dried rhizomes of P. tenuifolia (965.27 g) were extracted with 8:l(v/v) of 60% EtOH hot water for 2 h, this procedure was repeated twice. The extracts were then filtered and concentrated in vacuum into residues and lyophilized into powder to get the YZE (201.5 g) fraction. This was then suspended, and the liquid material was subjected to a macroporous resin column (1300 Version) and eluted with 50% EtOH, (v/v) to yield the fraction 50 (YZ-50, 48.4 g), the yield of the extract was 5.014% (w/w)."

There is a big differences in dosages between the 2 studies. From 0.1mg/Kg to 280mg/kg, that's a 2800x difference, so the extract exact preparation method is the key point missing here. 

In any case the data is quite impressive. 

The Saccharin preference (%) for mice given Chronic Mild Stress (CMS), improved slightly more when given RP, than when given Ketamine (Chart C)
The Immobility (s) for mice given Chronic Mild Stress (CMS), improved slightly more (less immobility) when given RP, than when given Ketamine (Chart D). 

Which seems quite compelling, although I wonder if this can be replicated in humans or not. 

According to the study RP is a NMDA antagonist (or at least does some sort of modulation there) and is a AMPA activator, (which are traits shared with Ketamine, and partially with GLYX-13 that just blocks NMDA receptors and increases AMPA receptor activity. Source: http://www.nimh.nih....e-effects.shtml )
 

What am I missing here? RP 10:1, 20:1 extract is fairly cheap, bought from Alibaba. Got a few quotations so far with Certificate of Analysis (most likely forged, but they eventually won't send salmonella or E-coli, or heavy metals on it) so it could allow people to try it out. 

Of course the raw extract cannot be matched to the preparation made in the articles above. What I question is what exactly did these preparation methods did to the extracts they used, in terms of added value. I know nothing about herbal extract preparation methods .. although I guess that it takes ... Something like this?: 



Any Walter White here that knows how to interpret the above studies' extract preparation methods?

and/or comments on this "herbal" approach viability? 

Attached Files

•  journal.pone.0088617.PDF   495.77KB   2 downloads
•  hu2010.pdf   770.49KB   0 downloads

Edited by opusensemble, 15 March 2016 - 01:59 AM.

[The Capybara]

I'm not trying to redirect this thread to another, but here is a short discussion (at the time of this posting), that complements this one.

Please note that the intranasal dose was less than 10% of the lower standard for IV use of GLYX

Granted it's only one data point, but it'd sure be nice to get some more points on the chart

 

http://www.longecity...orting-glyx-13/

[Reformed-Redan]

I just noticed that on alibaba, "Wuhan Hengheda Pharm Co., Ltd." offers NRX-1074 for sale. They have a good reputation on these forums and elsewhere of providing authentic and real products. 

 

Would anyone be interested in participating in a group buy from them?

 

I'm going to send a price quote for NRX-1074 from them and see what happens. Anyone else interested is welcome to do the same:

 

http://www.alibaba.c...chText=NRX-1074

[Reformed-Redan]

Unfortunately, after talking with them they do not have either GLYX-13 or NRX-1074 at this time. 

 

I will pursue this matter further as to whether they can make a custom synthesis of it.

[The Capybara]

I'll order a kg of Radix Polygalae extract in the next week if you like.

I'll also find out the extraction method. I trust this source and have used them many times without issue.

[Izan]

 

Unfortunately, after talking with them they do not have either GLYX-13 or NRX-1074 at this time. 

 

I will pursue this matter further as to whether they can make a custom synthesis of it.

 

Could you perhaps ask them if they can produce d-deprenyl? 

[Nick Kyz]

I would consider organizing this group buy. What did Wuhan say, Redan?

Edited by Nick Kyz, 31 March 2016 - 07:29 AM.

[Reformed-Redan]

I would consider organizing this group buy. What did Wuhan say, Redan?

That they don't have it at this time... But, they did say they were working on it. I wouldn't count on them, at least not in the near term. The synthesis requires a special and hard to obtain intermediate from what I gather. 

 

I have a link for that intermediate; but, it alone costs quite a bit also.

 

Best regards.

[Reformed-Redan]

I would consider organizing this group buy. What did Wuhan say, Redan?

Any updates on this Nick?

 

Thanks.

I posed a reddit topic on the 90% reduction in learning time for rats found in 2 papers.

 

Just some more interesting stuff outta this amazing compound.

 

https://www.reddit.c...for_mice_by_90/

[ceridwen]

Is it too late to join?

[Reformed-Redan]

Is it too late to join?

The more the merrier.

[Reformed-Redan]

Does anyone have contact information to the user who used to post here under the nick: "Googletarian"? I suppose a reputable Polish lab would be able to synthesize this given enough interest and funding, all of which should not be an issue at this point.

 

Cheers.

Edited by redan, 02 April 2016 - 06:25 PM.

[Irishdude]

Does anyone have contact information to the user who used to post here under the nick: "Googletarian"? I suppose a reputable Polish lab would be able to synthesize this given enough interest and funding, all of which should not be an issue at this point.

 

Cheers.

 

Wasnt he the lad who tried to scam scienceguys groupbuy? The lab broke up and never refunded the cash?

[Reformed-Redan]

 

Does anyone have contact information to the user who used to post here under the nick: "Googletarian"? I suppose a reputable Polish lab would be able to synthesize this given enough interest and funding, all of which should not be an issue at this point.

 

Cheers.

 

Wasnt he the lad who tried to scam scienceguys groupbuy? The lab broke up and never refunded the cash?

 

Did that actually happen? Wow...

 

Well, if anyone knows a lab that would be able to synthesize this, please let us know. (I'm not handling the group buy though)...

[Nick Kyz]

I arrived at the same conclusion as you redan. I'm not sure a polish lab is necessarily viable, though I could look into it.

[franbird]

I'd like to join this group buy if at all possible

[jefferson]

I'd like to join too. It seems though like this isn't much off the ground unfortunately, but count me in when you determine the price of meting this stuff out.

[franbird]

TLR said that their next batch of NRX-1074 would be ready early May

[Adr1n]

I think no one reported yet from the first NRX-1074 batch from them, that makes it hard to know about the quality of the compound they are synthetising

[Nick Kyz]

I'd be very curious to hear reports. From the research it seems a comparatively large dose it required.

[Reformed-Redan]

Not to hate on TeamTLR, but unless they're able to produce a third party analysis I wouldn't buy from them...