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Intranasal (Snorting) GLYX-13

antidepressant insufflating glyx glyx13 glyx-13 rapastinel

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#1 The Capybara

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Posted 17 March 2016 - 02:35 AM


I had some Glyx-13 laying around and had previously tried injecting it subcutaneously.

I tried it subcutaneously before giving it a try IV just to make sure that everything was OK.

I passed the solution through a 0.22 micron sterile syringe filter prior to using.

There was a substantial amount of pain and inflammation that lasted several days, and this resulted in substantial skin discoloration at the injection site that lasted a few months.

Needless to say, I didn't move on to an IV trial for myself due to the inflammation, and just put the compound into a deep freeze.

 

A few months passed, and after a few miserable days of a deep funk, I decided to revisit the GLYX.

I decided to try snorting it. Didn't even weigh it. Just took a small pinch with my fingers and went for it in one nostril.

There was a substantial burning, but it was tolerable.

In about an hour the funk largely lifted.

In about another hour it was back and so I tried a larger dose and used both nostrils.

Same deal, except the effect was more profound.

There was almost no depression at all.

It's been a few hours and the effect is lasting. If it does revisit, as I expect it will, I'll just take some more.

 

Just wondering if anyone else has tried this route of administration?

 



#2 Adr1n

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Posted 17 March 2016 - 04:16 PM

How long did the effects lasted? Keep us informed

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#3 The Capybara

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Posted 17 March 2016 - 04:35 PM

The antidepressant effects seem to last longer each time I take it.

First time only lasted about an hour, but the effect was pretty dramatic.

The second time it lasted a few hours before the depression began to revisit.

The third time it lasted overnight, and still remains active at the time of this posting.

Mornings are the worst for me, and for the first time in weeks I awoke feeling normal.

 

This article seems to indicate that GLYX-13 should be active intranasally and I'd have to agree.

 

http://www.nature.co...pp2012246a.html



#4 uppercut1991

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Posted 17 March 2016 - 04:45 PM

Nyles7,

I havent tried glyx-13 yet but i would love to.

Where did you get it?Is it legitimate?



#5 lostfalco

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Posted 17 March 2016 - 04:54 PM

Very interesting, Nyles. Thanks for the info on intranasal glyx! I checked your site but didn't see glyx for sale. http://www.nyles7.com/   Are you thinking about stocking it anytime soon?


Edited by lostfalco, 17 March 2016 - 04:55 PM.


#6 The Capybara

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Posted 17 March 2016 - 04:58 PM

I had this batch made.

It is absolutely legitimate, but tested at 95% purity.

If I continue to use this, and I don't see why I wouldn't, I'd like to try to get a higher purity batch if possible.

Certainly someone else on Longecity had this synthesized or organized a group buy....I would think.



#7 The Capybara

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Posted 17 March 2016 - 05:19 PM

I changed my Longecity username so it wouldn't appear that there was a conflict of interest since I do offer other compounds.

The effects of GLYX are pretty profound for me, and I don't want to seem as though I'm trying to push a product.

As lostfalco points out, I don't offer this one (it's under patent).

Sometimes, (in truth, very rarely) a compound has such profound effects that it's worth mentioning and getting other people's experiences.

This may be one of those rare times.

So far, it's been dramatically effective, very fast acting, and has had no side effects except for the burning sensation upon insufflating.

Will the positives fizzle out eventually?

Will side effects show up?

Is this compound just a good match for me and maybe not for others?

Maybe we should find out.

My depression has been extremely resistant to treatment. so this response is very unusual. Then there is the speed of the response.


Edited by The Capybara, 17 March 2016 - 06:16 PM.

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#8 Adr1n

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Posted 17 March 2016 - 05:39 PM

It's an interesting anecdotal experience, there are not many Glyx-13 reports out there, and this appears to be one of the most promising substances for the upcoming years, hopefully, it truly is. So keep informing next days/weeks after it builds up in your body. I think I read a single dose of Glyx should keep you good a week or so, but don't know if that's exclusively for the IV dose. 



#9 lostfalco

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Posted 17 March 2016 - 08:33 PM

I changed my Longecity username so it wouldn't appear that there was a conflict of interest since I do offer other compounds.

 

Well, I have no affiliation with you so I'm happy to recommend people check out your site. =) I've ordered from Nyles a number of times and have always had a good experience. Check out his stuff at http://www.nyles7.com  and on ebay.   http://www.ebay.com/usr/nyles7

 

I don't mean to derail this thread (glyx looks very interesting) but for depression, have you looked into intranasal insulin? I just finished an 8 week run of it and it was very mood enhancing (even though I don't struggle with depression). You can actually buy it over the counter without a prescription at Walmart for $25 (Novolin R). It's been tested fairly extensively in humans and is a promising treatment for depression, learning/memory disorders, Alzheimer's, etc. Might be worth a try if nothing else (other than glyx) has worked for you. Just figured I'd share since I've benefitted from your store. =)


Edited by lostfalco, 17 March 2016 - 08:35 PM.

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#10 The Capybara

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Posted 19 March 2016 - 03:49 AM

Thanks lostfalco for the trust!



#11 The Capybara

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Posted 19 March 2016 - 04:53 AM

Here's the latest update, both good and bad.

The latest "snort" of GLYX-13 has lasted about 24 hours so far, and continues to be effective.

It is completely 100% effective and totally transparent.

By transparent I mean that there is no feeling of being drugged, emotionally constrained or blunted, and in fact, it's like nothing I've ever tried before.

Tianeptine and selegiline worked for a few years, They'd kick in quickly (a few minutes to an hour or so) and there was a good feeling that tended to replace the decline in depression.

GLYX seems to remove the depression completely and cleanly, leaving a void where the depression used to be.

The depression is not replaced with anything. It's simply gone. You'd probably have to try it to understand what I'm trying to covey. It's unique.

Never has a compound so completely removed my depression, and were talking major, stay in bed for days, depression, and did so in under two hours.

Each time I snort the GLYX the effect lasts longer.

First time it was approximately an hour of relief. This time it has been 24 hours and it's still working.

My memory is amazing. I'm able to recall obscure names from my past almost effortlessly. Other antidepressants had never done this.

I don't think it's just removing the depression that allowed for this enhanced cognition; this compound may indeed be a true, fast acting and noticeably efficacious nootropic.

I'm glad that my brain is still working. I had my doubts.

We'll have to wait for others to chime in on the nootropic effects.

Most discussions on this website, and other sites, go nowhere. I think this one is for real.

Sounds perfect. So what's the downside?

 

Pain!

It's got to be from the unknown 5%. The contaminants.

It burns incredibly when injected and insufflated.

Not only that, but nearly all my muscles ache to such a degree that I considered going to he hospital last night.

I'm not one to casually do that

 

I couldn't even sit up, my abdomen hurt that much, and I was painfully coughing all night and am still doing so.

My mind was ready to go out and live for the first time in months, and my body shut that idea down right away.

I can't imagine purer GLYX doing this. Who'd want to market a compound that caused these immediate side effects?

 

As I mentioned at the start of this thread, the purity of this batch is 95%

The burning and inflammation is incredible. All my muscles don't just ache, they hurt.

Even my arms and chest.

While I feel great mentally, physically I feel like sh*t.

 

I have to stop this trial and find purer source of GLYX.

Anyone know of a legitimate and high grade source?

This compound, in a purer form, is worthy of a group buy by anyone that has refractory depression.

Again, this stuff worked on me in about 2 hours, without having to inject, and each time I administered it, it lasted much longer than the previous time though the dose did not increase appreciably.

I'm not going to organize the buy, but I'll certainly ante up for a share.


Edited by The Capybara, 19 March 2016 - 05:36 AM.


#12 Reformed-Redan

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Posted 19 March 2016 - 08:44 AM

Do you think the more potent and longer lasting version called 'NRX-1074' would be possible to make? I've been trying to get that one for a while now. It's supposto be 1000x more potent than GLYX...

 

"NRX-1074 is several thousand times more potent than GLYX-13, and preclinical studies have shown that it is active when administered orally. NRX-1074 has in vivo mechanistic activity similar to GLYX-13, including a ketamine-like efficacy signature with rapid onset and long-acting duration of antidepressant-like effect. Similar to GLYX-13, in animal studies NRX-1074 has demonstrated good safety with no signs of CNS-related side effects. Naurex's initial development focus for this fast-acting, potent, orally available compound is in major depression.

"NRX-1074 is the first orally available agent from our novel platform of highly selective NMDA receptor modulators to enter human trials," said Derek Small, CEO of Naurex. "In preclinical studies it has demonstrated a similar profile to GLYX-13, with the ketamine-like attributes of rapid onset and prolonged antidepressant effect but without any evidence of ketamine's limiting side effects. We are delighted to have begun testing NRX-1074 in humans at the same time that our Phase IIb trial of GLYX-13 is proceeding well. We expect to report results from the Phase I study in 2014."
In the Phase IIa trial, a single administration of GLYX-13 produced statistically significant reductions in depression scores in subjects who had failed treatment with current antidepressants. The reductions were evident within 24 hours and persisted for an average of seven days. A measure of the antidepressant efficacy of GLYX-13 observed at 24 hours and at seven days was nearly double that seen with most antidepressants after 4-6 weeks of repeated dosing. In this study, GLYX-13 was also well tolerated. Reported side effects were mild to moderate and were consistent with those observed in subjects receiving placebo. GLYX-13 did not produce any of the schizophrenia-like psychotomimetic effects associated with other drugs that modulate the NMDA receptor.1,2"

 

See a list of interested people here: (quite a few)

 

http://www.longecity...roup-buy/page-1



#13 Reformed-Redan

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Posted 19 March 2016 - 08:55 AM

1g of NRX-1074 could last a lifetime if the above claims are true, with a half-life of 7 days. I really don't see why one would not want to get it given your claims about its older version of GYX-13. Ehh.



#14 The Capybara

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Posted 19 March 2016 - 10:19 AM

It's a tough molecule to synthesize. This can clearly be seen by the lack of legitimate Chinese vendors right now even though the structure is now known.

No doubt it will indeed show up from high quality labs at a pretty high price per gram, which may indeed translate to a lower price per dose in this case.

My question is:

If you find something that works perfectly (assuming all the side effects from the GLYX are from the lack of purity), why try and improve near perfection?

The receptor avidity will never be the same between the compounds, the metabolites will differ, specificity will likely differ, etc.

If it ain't broken, why fix it?

Now if you had tried GLYX and it didn't work for you, then looking for something more effective is reasonable.

GLYX is far more documented than NRX-1074

Premarketing hype rules the day with new compounds.

The reality of Prozac and atypical antipsychotics didn't come close to the marketing claims, yet they were magic, revolutionary, at this equivalent stage of development, as was Vioxx which killed more Americans than the Vietnam War.

I'm not saying NRX will play out that way. I am saying that GLYX seems to work amazingly well and will not likely play out that way.

I think it's been around for 20-30 years. Don't quote me on that without fact checking.



#15 Reformed-Redan

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Posted 19 March 2016 - 11:00 AM

I'd be happy with GLYX-13; but, NRX-1074 is worth the effort since it's much more stable than GLYX-13 and can be taken orally if one doesn't want to use it intranasally, which would boost effectiveness. Your call though as I don't have the funds to make NRX-1074. I do know where you can get the intermediates to make it though. If it interests you I can PM details to a peptide based company that could make a small batch of NRX-1074. Then you can sell it in the miligram range. Best regards.



#16 Reformed-Redan

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Posted 19 March 2016 - 11:03 AM

Also, from what I gather there is a greater amount of interest in NRX-1074 rather than GLYX-13, which has been around for a while. It would sell pretty well also from what I gather in regards to the link I sent you.



#17 The Capybara

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Posted 21 March 2016 - 05:10 AM

Just a quick update:

I'm on day 3, post insufflation of GLYX-13, and have absolutely no hints of recurring depression.

I would estimate the average snort to be in the range of 10-30 mg.

I'm sure that depression will arrive again soon, as "the black dog" has been my constant life companion, but knowing that I'm 2 hours from relief with one "snort" of some more GLYX powder makes this a trivial issue.

Why isn't everyone trying this?

I hope I don't begin going evangelical on this one....however.....  :|?


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#18 Reformed-Redan

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Posted 21 March 2016 - 11:11 AM

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



#19 Reformed-Redan

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Posted 21 March 2016 - 11:28 AM

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.


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#20 The Capybara

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Posted 21 March 2016 - 10:49 PM

So day 4 rolled around and it took the typical hour or so to get out of bed, not motivated to go outside.

Back to baseline I guess.

Took out the GLYX and it looked like a sheet of ice.

Seems it's extremely hygroscopic, which is strange considering its limited solubility in water.

It's far more hygroscopic than tianeptine.

So I'll slowly migrate to a hardware store and pick up some "DampRid" (Calcium Chloride, a potent and non-toxic desiccant) and dry the GLYX out and pulverize it into a powder with a mortar and pestle and take another dose.

I did find a source for 98%+ GLYX, but the burning and inflammation from my current 95% batch may just be an inherent property of the GLYX itself.

I'll know more when the next batch is synthesized.

So far that is the worst side effect, in fact, the only side effect and I'll take that easily over the standard side effects for other antidepressants, that really aren't true antidepressants for most.

You'll realize that more than you do now if GLYX does indeed work for you.


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#21 The Capybara

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Posted 22 March 2016 - 04:33 AM

Was feeling my old self. Depressed, pissed off at trivial things, a feeling of "what's the point?" to pretty much everything

I had been desiccating the GLYX (see above) and the glass-like sheets were now brittle and cracking rather than bending, so I cracked up a bunch and......

 

T=00:00 (7:35pm) Insufflated 30mg total weight of GLYX-13 (95% purity) split between both nostrils. Sort of chunky in consistency. Certainly not a fine powder. Burns upon inhalation as always. Each subsequent sniff seems to rekindle the burn.

T=00:05 Feeling "something" which included some minor and temporary anxiety. Maybe this is mildly psychoactive. Nothing even close to ketamine though.

T=00:15 Noticing an irritation in the back if my throat. In an effort not to have to go through another all night, post GLYX, coughing bout, I'm sipping on Silk Chocolate Soymilk hoping I will wash the residue out of my throat as it drips from my sinuses and before my lungs get a hint of it.

T=00:30 Most certainly something mildly psychoactive. Could be the unknown 5% or the GLYX itself. I could probably still crank out some calculus, but might feel a little strange lost in a crowd. Still pissed off and grouchy.

T=00:40 Feeling fairly relaxed and could probably even take a nap.

T=01:00 Just checking in at the hour mark. More calm, though the night is getting quieter. Ah, there's some noise. Yup, still irritable.

T=01:20 I've been progressively feeling hotter over the past 20 minutes or so. Turns out that it is actually really hot here in Arizona and I just hadn't noticed all day. Had a fleeting thought of maybe going on a short nighttime neighborhood bike ride.

T=01:35 I don't want to jump the gun here, but I think I could actually go out for a bike ride. This would have been essentially impossible an hour and a half ago. I'm still a little irritated by gratuitous noises, but can better deal with them and don't obsess and ruminate. All added GLYX anxiety has dissipated. I'm not sure when that happened, but there is no feeling of having been drugged, or any noticeably altered thought patterns. 

T=01:45 OK, I'm going to call this moment as the moment of being subjectively fully functional. Maybe under stresses some depressive behavior might emerge, or maybe I couldn't do serial sevens as fast as I should, but mentally I feel fine just sitting here. My abdominal muscles do hurt a bit from minor coughing, but this would have been trivial if I had not really strained them the other night (see above).

T=02:00 To celebrate hour number 2, I'm going for a short bike ride :-)

And that's how GLYX-13 seems to go for me at this time.


Edited by The Capybara, 22 March 2016 - 04:36 AM.


#22 sant2060

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Posted 22 March 2016 - 07:26 AM

What is the price for 98% pure glyx-13, and can you share source over PM?

Didnt notice, did you try sublingual route?

Does glyx-13 help you with anhedonia (if you have it)? Depression I can control, but anhedonia is killing me.

#23 stillwater

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Posted 25 March 2016 - 01:05 AM

No rush or anything, but I have to say I do eagerly await your next posts and future accounts of your trial with this, pretty fascinating, thanks for doing it.   I am a bit curious if you ever tried low dose ketamine for depression and how it might compare to GLYX-13 if you did. Feel free to pm me if you'd rather not discuss that here.

 

 

 

 

 



#24 Adr1n

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Posted 25 March 2016 - 01:40 AM

It surprises me the lack of ketamine infusion anecdotal reports out there, taking in count the number of clinics offering the treatment has multiplied.

#25 The Capybara

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Posted 26 March 2016 - 06:40 AM

OK, here's an important update to this informal testing....

I was so careful not to get any of this latest GLYX inhalation into my lungs, but two days after the test I was coughing and my abdominals were in pain once again.

It's only today (March 25th) that I can move without pain.

I don't know what is going on. The coughing is always really intense, chronic, and as they say in medicine: "Productive"

I've no idea why this is happening.

 

It seems really effective for depression, but feeling either mentally well or physically well, but not both, frankly sucks.

 

I will wait until the purer batch arrives and try this insufflation thing one last time. If that fails and all indicators show that this is a good quality batch, I'll try injecting once again and report back.

 

In answer to the two questions that went unanswered....Sublingual administration didn't seem to work. It may prove to be very effective, but like IV dosages, it would likley have to be substantially larger than the inhalation dose. I didn't have this much available.

 

As for anhedonia, I just don't know. The coughing kicks in and just ruins the day(s), then the pain tends to taint one's view of the world. Let me put this question on hold until the new batch, and new round of experimentation, moves ahead in the next few weeks.

 



#26 sant2060

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Posted 26 March 2016 - 10:34 AM

Did you try antitussives to ease coughing?
Not a long term solution, but maybe can make experience more acceptable until you try purer batch.

#27 lostfalco

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Posted 29 March 2016 - 10:56 PM

Recent glyx study. =)

 

https://www.ncbi.nlm...pubmed/26997507

 

Curr Neuropharmacol. 2016 Mar 21. [Epub ahead of print]

The Development of Rapastinel (Formerly GLYX-13); a rapid acting and long lasting antidepressant.

Abstract

Rapastinel (GLYX-13) is a NMDA receptor modulator with glycine-site partial agonist properties. It is a robust cognitive enhancer and shows rapid and long-lasting antidepressant properties in both animal models and in humans. Rapastinel was derived from a monoclonal antibody, B6B21, is a tetrapeptide (threonine-proline-proline-threonine-amide) obtained from amino acid sequence information obtained from sequencing one of the hypervariable regions of the light chain of B6B21. Rapastinel was found to be a robust cognitive enhancer in a variety of learning and memory paradigms and marked antidepressant-like properties in multiple models including the forced swim (Porsolt), learned helplessness and chronic unpredictable stress. Rapastinel's rapid-acting antidepressant properties appear to be mediated by its ability to activate NMDA receptors leading to enhancement in synaptic plasticity processes associated with learning and memory. This is further substantiated by the increase in mature dendritic spines found 24 hrs after rapastinel treatment in both the rat dentate gyrus and layer five of the medial prefrontal cortes. Moreover, ex vivo LTP studies showed that the effects of rapastinel persisted at least two weeks post-dosing suggesting that rapastinel has significant effects on metaplasticity processes that may help explain the long lasting antidepressant effects of rapastinel seen in the human clinical trial results.

 


Edited by lostfalco, 29 March 2016 - 10:57 PM.

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#28 Killword

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Posted 02 April 2016 - 11:11 PM

Very interested in this compound if a good synthesis is found.  Also, if it's used intranasally, insufflating the powder is asking for respiratory problems, especially if it's hydrophobic at all.  In a suitable carrier/solution it will at least be able to be cleared away instead of sticking in your sinuses like grit and potentially causing tissue damage.  I would love to find out if it works intrarectally since that usually has much better bioavailability than anything not involving a needle and is much safer than intranasal (if inconvenient and troublesome for most).  If anyone knows of any vendors please PM me... it was available a year or two ago for a brief period but not sure how pure that was.



#29 Nick Kyz

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Posted 07 April 2016 - 02:33 AM

I would consider a group vendor buy with you Nyles. For this or NRX-1074. I'll send you a PM.



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#30 newmind

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Posted 09 April 2016 - 06:16 AM

"two days after the test I was coughing and my abdominals were in pain once again."

GLYX-13 is a peptide.  Most peptides are produced in the form of salts - i.e. with a counterion.  TFA (trifluoroacetic acid) is the most typical counterion used for synthesis and HPLC purification of peptides.  If the counterion is not specified, it's likely TFA.  TFA is a corrosive acid and likely to be substantially more biologically toxic than acetic acid.  TFA should be removed / substituted with another counterion for anything that is going to be tested in vivo.


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