659 replies to this topic

[Adr1n]

Also, if the lab wants 50% upfront, why do participants have to pay the full price upfront? I am not being difficult, simply fair.

Because who will answer for the money if any of the participants doesn't want to pay the other 50%

But I'm curious too about what the lab have to say about the complexity of the compound, it may be hard to synthesise but not imposibe though.

Edited by Adr1n, 02 June 2016 - 02:42 PM.

[dankis]

As far as I know, it is being synthesized by polish university team led by a professor. IMO it is really hard to get more reliable source.

Edited by dankis, 02 June 2016 - 05:41 PM.

[tolerant]

 

Also, if the lab wants 50% upfront, why do participants have to pay the full price upfront? I am not being difficult, simply fair.

 

Because who will answer for the money if any of the participants doesn't want to pay the other 50%

 

 

Any participant who doesn't pay the other 50% doesn't get the substance. I'm sure once it's actually synthesised and tested, new people will be swarming like flies to get their hands on the compound.

Edited by tolerant, 02 June 2016 - 11:32 PM.

[deetown]

Is this group buy open?

[Nick Kyz]

Originally we were going to pay the full price upfront. I renegotiated that we would pay the remainder after we verified the structure and purity. We could have refunded half the payment at that point, but frankly it would be a logistical nightmare and nobody is being compensated for this. 

 

@deetown technically no but in exigent cases I'm giving up part of my order to let other buyers in. 

Edited by Nick Kyz, 03 June 2016 - 12:28 AM.

[opusensemble]

Also, if the lab wants 50% upfront, why do participants have to pay the full price upfront? I am not being difficult, simply fair.

 

 

If you check this thread history, considering (last time I checked) Nick is supporting the costs of 3rd party lab analysis or the costs of the minimum quantity for analysis (can't remember which), shows the group buy is a non-profit initiative that was setup only through the good will of Nick and Redan. None of us would have had the patience of Madre Teresa to do what they're doing and assume the responsibility of the shipping logistics alone. Even less second layer of complexity on reimbursement logistics. If you put yourself in the organizer's shoes you'll understand the need for keeping it simple. 

Group buying means risk-sharing. 

Edited by opusensemble, 03 June 2016 - 01:14 AM.

[tolerant]

I don't want to spread panic in this group buy -- at this juncture it would be totally counter-productive. I have paid my $400 and I would like some measure transparency. All we know right now is that the synthesis is supposed to be finished in July. Now this is a very difficult compound to synthesise. It contains a special building block amino acid, which I won't name here. The technical problem is that this special amino acid is not produced and sold like many special amino acids, such as for example, methylated amino acids or D- amino acids. In other words, to synthesize NRX-1074 you have to also synthesise that special block. Only about 2 peptide synthesis companies in the entire world also synthesize their own amino acids. That means that the Polish lab doing the synthesis need to purchase this building block. So an intermediary step would be for the organisers to provide an invoice for this block. Regardless of whether the lab purchases it or synthesises it themselves (extremely unlikely), they would perform H-NMR, MS and HPLC tests on that block. So another intermediary step would be for the organisers to provide us with the appropriate reports for those tests.

Edited by tolerant, 07 June 2016 - 03:44 AM.

[Reformed-Redan]

I don't want to spread panic in this group buy -- at this juncture it would be totally counter-productive. I have paid my $400 and I would like some measure transparency. All we know right now is that the synthesis is supposed to be finished in July. Now this is a very difficult compound to synthesise. It contains a special building block amino acid, which I won't name here. The technical problem is that this special amino acid is not produced and sold like many special amino acids, such as for example, methylated amino acids or D- amino acids. In other words, to synthesize NRX-1074 you have to also synthesise that special block. Only about 2 peptide synthesis companies in the entire world also synthesize their own amino acids. That means that the Polish lab doing the synthesis need to purchase this building block. So an intermediary step would be for the organisers to provide an invoice for this block. Regardless of whether the lab purchases it or synthesises it themselves (extremely unlikely), they would perform H-NMR, MS and HPLC tests on that block. So another intermediary step would be for the organisers to provide us with the appropriate reports for those tests.

I think I know of what peptide you talk about. Boc-®-alpha-benzyl-proline ?

 

There are suppliers for it online and after exhaustive searching I found it available from a website. Not cheap.

[Nick Kyz]

It is a coincidence that I sent the lab a request for an update today, with the intention to post what I hear. 

 

These are the steps of synthesis for those inclined:

https://www.dropbox....thesis.png?dl=0

 

I am well aware of the precursors involved. We were not invoiced for them. We placed a purchase order for NRX. Normally the lab operates on Net30 but we had no prior experience with them. Would you like me to request reports on the precursors? If anyone has any other questions concerning the synth you can let me know here and I will forward them.

 

Please don't interpret radio silence for being lackadaisical. 

 

Edited by Nick Kyz, 07 June 2016 - 04:41 AM.

[Nick Kyz]

Here is the response I received:

 

Attached is the route we are using. We have synthesized the intermediate 13 already. You can take a look at attached NMR.

Now the difficulty lies in the condensation between material 6 and material 7. We have tried  the condensation agents, such as HATU, EDCI, TBTU, PyBOP, COMU, all turned out to be not good. We are now trying T3P today, wish to find a proper condensation agent. Once the condensation is completed, there shall be no big problem. If your team has better suggestion, please tell us. Thank you for your kind support.

Have a wonderful day!

 

 

Route: https://www.dropbox....thesis.pdf?dl=0

I-13 HNMR: https://www.dropbox....iate13.pdf?dl=0

 

Do any of the organic chemists among us have a suggestion for condensation agent?

Edited by Nick Kyz, 07 June 2016 - 05:36 AM.

[Reformed-Redan]

You can suggest to them PyBrOP?

[samson75]

One question; can anyone point me to results of tests that demonstrate the effeciency of NRX-1074

for depression and/or anxiety ?

I know it's been tested for quite a long time but i can't find anything.

Is it really the "big thing" against that condition based on what you read, especially for people like me

who don't get relief from traditionnal antidepressants?

 

Among the members who participated in this group buy; is it for scientific research or are you trying

to be cured from depression ?

 

[Nick Kyz]

Here's what GS turns up: https://scholar.goog...dt=1,5&as_sdtp=

 

Here are the clinical trials: https://clinicaltria...4&Search=Search

[samson75]

Thanks Nick.

[DaoSmith]

Hi is this group buy still open? I would be very interested in jumping on

[uppercut1991]

Hey Nick, did you get any news from the lab? I'm curious if they managed to resolve issue with condensation. If you know anything keep us posted. 

[Nick Kyz]

Group buy is no longer open. I'll get a synth update in a week, I don't want to give the impression of inexperience.

Edited by Nick Kyz, 16 June 2016 - 02:17 AM.

[franbird]

Not long now 

[Nick Kyz]

The lab is still having trouble with condensation so they've switched to the following new synthesis route:

 

https://www.dropbox....sation.png?dl=0

[Reformed-Redan]

The lab is still having trouble with condensation so they've switched to the following new synthesis route:

 

https://www.dropbox....sation.png?dl=0

 

 

This is why dealing with a university lab was in the end the better option despite higher costs. They haven't given up on the synthesis and looks like they are adamant about making it happen.

 

Keeping fingers crossed.

[Babakk]

First of all I would like to admit that I haven't read the whole thread here so please bear with my relative ignorance.

 

I have read that Rapastinel was scheduled to be released in the market by the 1st half of 2016. Furthermore, from past experience I know that usually Europe is much quicker in making new drugs available than US. 

 

Can some one tell me if licenced Rapastinel (not as research chemical)  is available out there somewhere and if not when will it be?

 

I suffer from MDD and have tried all the others and many off their combinations throughout the last 25 years(as well as years of therapy, ECT and even VNS). My CT scans have also confirmed that the atrophic changes in my brain are in excess of what should be for my age(57). Fortunately I am told that it is not progressive. So, I am anxious to try this new class of antidepressant hoping that I will finally have some relief from this terrible disorder in the autumn of my life.

 

Thanks

[Der Springende Punkt]

First of all I would like to admit that I haven't read the whole thread here so please bear with my relative ignorance.

 

I have read that Rapastinel was scheduled to be released in the market by the 1st half of 2016. Furthermore, from past experience I know that usually Europe is much quicker in making new drugs available than US. 

 

Can some one tell me if licenced Rapastinel (not as research chemical)  is available out there somewhere and if not when will it be?

 

I suffer from MDD and have tried all the others and many off their combinations throughout the last 25 years(as well as years of therapy, ECT and even VNS). My CT scans have also confirmed that the atrophic changes in my brain are in excess of what should be for my age(57). Fortunately I am told that it is not progressive. So, I am anxious to try this new class of antidepressant hoping that I will finally have some relief from this terrible disorder in the autumn of my life.

 

Thanks

 

Unfortunately, Rapastinel might be some years away from an approval. It received "FDA Breakthrough Therapy Designation" but as far as I know a phase 3 study has not yet started. Intranasal Esketamine from Janssen will be the first NMDA based AD on the market if anything works well (maybe in 2018).

[samson75]

@Babakk : i'm on the same boat. Over 10 years of depression and generalized anxiety.

And from early 2016 regular mornings panic attacks.

 

Only partial response to antidepressors, same with anti anxiety medications. But complete

side effects : fatigue, memory loss, blurred vision etc.

I've made 8 weeks of magnetic cranial stimulation at a hospital without any results.

Not to mention indifferent psychiatrists who don't seem to know anything to do besides

telling me to up my AD doses.

They look at me like if i was crazy when i mention those new ketamine derived medications

that are about to enter the market by around 2019. They pretend to not know anything about

them and tell me to stop reading too much stuff on the net...

My situation is getting worse and somedays it's just a living hell.

 

The only thing that keeps me going on is hope that those new AD will be game changers.

Glyx-13/Raspatinel : i'm going to take a close look at The Capybara's experience on that thread :

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

NRX-1074 : we'll soon see among the group-buy participants if it does the trick.

Janssen's Esketamine : unfortunatly i don't have any informations on that one.

 

If something positive comes from those three ones; i'm ok to suffer two or three years more

waiting for them to come on the french market.

 

 

Edited by samson75, 22 June 2016 - 08:32 AM.

[Reformed-Redan]

@Babakk : i'm on the same boat. Over 10 years of depression and generalized anxiety.

And from early 2016 regular mornings panic attacks.

 

Only partial response to antidepressors, same with anti anxiety medications. But complete

side effects : fatigue, memory loss, blurred vision etc.

I've made 8 weeks of magnetic cranial stimulation at a hospital without any results.

Not to mention indifferent psychiatrists who don't seem to know anything to do besides

telling me to up my AD doses.

They look at me like if i was crazy when i mention those new ketamine derived medications

that are about to enter the market by around 2019. They pretend to not know anything about

them and tell me to stop reading too much stuff on the net...

My situation is getting worse and somedays it's just a living hell.

 

The only thing that keeps me going on is hope that those new AD will be game changers.

Glyx-13/Raspatinel : i'm going to take a close look at The Capybara's experience on that thread :

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

NRX-1074 : we'll soon see among the group-buy participants if it does the trick.

Janssen's Esketamine : unfortunatly i don't have any informations on that one.

 

If something positive comes from those three ones; i'm ok to suffer two or three years more

waiting for them to come on the french market.

 

 

I can ask Nick if he can make a spot for you...

 

Let's see what he says.

[samson75]

Thanks Redan but i already bought a 250mg spot weeks ago ! :-)

This is a too small dose i think but my objective is to see what

are the overall results for all the participants.

If there's really something impressive coming of this experience

i'll invest big money for the next group buy and will quietly wait for the original

licenced product to enter the european market.

 

Edited by samson75, 22 June 2016 - 09:12 AM.

[Reformed-Redan]

Thanks Redan but i already bought a 250mg spot weeks ago ! :-)

This is a too small dose i think but my objective is to see what

are the overall results for all the participants.

If there's really something impressive coming of this experience

i'll invest big money for the next group buy and will quietly wait for the original

licenced product to enter the european market.

Oh yea, just checked the participants and you already payed.

 

Nice.

 

Note that they used max 10 mg in their MDD treatment study. I don't know the effectiveness of it vs the 1 mg and 5 mg doses they used; but, if used intranasally I expect the 250 mg would still last quite a while...

[samson75]

I'll have to learn from you the intranasal technique. Do you have something planned ?

Would be interesting to know about the Janssen intranasal method with esketamine.

 

[Reformed-Redan]

I'll have to learn from you the intranasal technique. Do you have something planned ?

Would be interesting to know about the Janssen intranasal method with esketamine.

My preference for NRX over Ketamine is due to the fact that NRX-1074 has a longer half life, doesn't seem to develop tolerance, is a huge nootropic (see previous posts on that), and supposedly is very potent. Also, NMDA antagonism isn't for everyone. In so many ways it seems superior to ketamine...

 

As for intranasal. You can dissolve 100mg+ in 10 ml of liquid and one or two sprays into your nostrils while breathing in through your nose should do the trick. That would last you quite a while with a 7 day duration of positive effects from the compound. You can buy a spray bottle from Ceretropic along with some bacteriostatic water.

[samson75]

Thanks for the info. But 7 days of positive outcome, no tolerance, big nootropic effects etc. You seem

quite optimistic ;-) . I hope not too much !

As for Janssen i was talking about their product "esketamine" and not traditionnal ketamine.

I think it's quite close to nrx-1074.

[Reformed-Redan]

Thanks for the info. But 7 days of positive outcome, no tolerance, big nootropic effects etc. You seem

quite optimistic ;-) . I hope not too much !

As for Janssen i was talking about their product "esketamine" and not traditionnal ketamine.

I think it's quite close to nrx-1074.

Well, I've spent the last 5 years of my life reading research papers on nootropics, and since this is probably the last compound I am trying to get synthesized, I think it has been worth the years on reading and researching nootropic and antidepressant compounds. 

 

Anyway, I'm always excited about nootropics, haha.