659 replies to this topic

[franbird]

Any updates?

[samson75]

Yes, would be nice to know approximatively when we'll get the product.

[Nick Kyz]

We're still a way aways. I'll ask the lab for an update. Assuming they finish on time the synthesis should be complete mid July, then we'll need to receive the product and have it analyzed which will take another 1-3 weeks. My expectation is late July to early August will be when we can ship out parcels.

[samson75]

Nice, thanks Nick. I hope there won't be damage caused by summer heat during shipping (and by customs also ;-)  ).

[GreenWhite]

Is there any info if it's unsafe to mix Benzos with NRX? I'm asking since it's dangerous to mix Benzos with Ketamine and both are NMDA receptor antagonists.

[tolerant]

Is there any info if it's unsafe to mix Benzos with NRX? I'm asking since it's dangerous to mix Benzos with Ketamine and both are NMDA receptor antagonists.

 

If you mean that benzos (as opposed to NRX) are not NMDA receptor antagonists, they are not. They are (roughly speaking) GABA agonists. I administered ketamine (at the "golden standard" dose used in almost every study) while on about 4 mg of clonazepam and 225 mg of Lyrica. Lyrica is, strictly speaking, also not an NMDA receptor antagonist, although it works by diminishing excitatory currents caused by glutamate binding to NMDA. What I felt was almost exactly like feeling drunk. That said, when I was administering ketamine, I had already developed tolerance to the amount of benzos and Lyrica I was taking. It all depends on whether you get an effect from taking benzos. If you feel an effect, then anything you take which has the same effect (irrespective of how it works) will obviously increase the effect, and that can possibly be dangerous. With benzos, that includes other GABA receptor agonists like alcohol, as well as, like you say, NMDA receptor antagonists. But in my opinion it really depends on the dose. There's no interaction as such of which I am aware whereby one of these drugs will multiply the effect of the other. It's more like an additive effect. Like having two shots of vodka instead of one.

 

What I would do if I was concerned is let benzos wash out of your system (if you're able to do that without causing major withdrawal), and then try NRX. Alternatively, take a smidgen of NRX to begin with an assess the effects. I would also search clinicaltrials.gov to see whether persons taking benzos are excluded from participation in ketamine studies.

[samson75]

And SSRI's ? I'm taking venlafaxine, is it a problem ?

@tolerant : did you get improvement with ketamine ?

Edited by samson75, 07 July 2016 - 07:10 AM.

[tolerant]

And SSRI's ? I'm taking venlafaxine, is it a problem ?

@tolerant : did you get improvement with ketamine ?

 

I was also on SSRIs when I administered ketamine and nothing bad happened. I didn't notice any improvement. But it must be said that I administered ketamine obtained from the black market intranasally at the dose I calculated myself to be equivalent to the dose used in the IV studies, and I did that only once. The studies say although a lot of people will get a response after the first administration, other people will not improve until six infusions. I think in practice, ketamine is being administered over more than six infusions, sometimes significantly more, but I haven't read any studies where they did more than six.

Edited by tolerant, 07 July 2016 - 08:24 AM.

[tolerant]

I should have added that if you're concerned about NRX's interaction with any drug, it would makes sense to search clinicaltrials.gov for exclusion criteria in trials of NRX itself and GLYX-13, ahead of exclusion criteria for ketamine.

[samson75]

Thanks for the info.

[signsandwonders]

I've been following this thread but recent reports suggest ketamine's AD effect is not NMDA-related :(

 

How about a groupbuy for hydroxynorketamine?

[The Capybara]

If you can find a legitimate source, I'll front the cost of the group buy (within reason of course).

[tolerant]

I've been following this thread but recent reports suggest ketamine's AD effect is not NMDA-related :(

 

How about a groupbuy for hydroxynorketamine?

 

Why a sad face sign? What's so bad about ketamine's AD effect not being NMDA-related? 

 

Hydroxynorketamine (HNK) is ketamine stripped of its psychotomimetic and analgesic effects and is purportedly responsible for ketamine's AD action. I agree that it follows that ketamine's AD action is not mediated by NMDA, because HNK has very weak binding affinity for the NMDA receptor.

 

Anyway, a fair while back I did some research on HNK and approached one German lab for a quote. The quote I got was 76,000 AUD for 25 grams each of (2S,6S)- and (2R, 6R)-stereoisomers of HNK (which are the relevant substances involved in depression research). During my research, I unearthed the process by which it's synthesised, which I communicated to the lab (although I have no idea whether that's the process they based their quote on). But I will spell out the process here together with the papers I relied on:

 

1. First, (R,S)-noketamine is prepared using modification of the method described in Chang Hong and Davission (enclosed). The modified synthesis is described in supplementary material to Moaddel et al. (enclosed; the supplementary material is enclosed as mmc1.doc and mmc2.doc, with the latter relevant to the synthesis).

 

2. (2S,6S)- and (2R, 6R)-stereoisomers of hydroxynorketamine are then prepare from (R,S)-norketamine as described in Leung and Baillee (enclosed).

 

3. The two stereoisomers are synthesised and isolated as described in Woolf et al. (enclosed).

 

This three-step process is itself described in Moaddel et al on page 1894 under section 2.1 Standards, and is referred to in Paul et al (enclosed) on page 150 under section Materials.

 

I should also note that stereoisomers of ketamine are likely to be scheduled and regulated in the same manner as ketamine itself is. So this group buy may work inside a customs-free zone like the EU only (unfortunately I don't reside inside the EU).

 

Finally, while we're off the subject, I would invite everyone to look at this thread for a promising drug in development which is already available to buy from certain vendors, and this thread, which I started to generate interest in a group buy of another promising drug in development.

Attached Files

•  HNK_1.zip   1.9MB   1 downloads
•  HNK_2.zip   1.71MB   1 downloads

[signsandwonders]

Thanks for the info!

 

 

I've been following this thread but recent reports suggest ketamine's AD effect is not NMDA-related :(

 

How about a groupbuy for hydroxynorketamine?

 

Why a sad face sign? What's so bad about ketamine's AD effect not being NMDA-related? 

 

 

Because people hoped NRX would work like Ketamine

[MoreNowAgain]

I would be very interested in a group buy for hydroxynorketamine

[GreenWhite]

I'm glad it isn't like ketamine because i didn't get an effect After six infusions.

My biggest hope is that nrx will help me building memories and help my cognication.

Edited by GreenWhite, 12 July 2016 - 06:34 PM.

[samson75]

@GreenWhite :

hello, could i ask you where you were able to try ketamine for depression ? Maybe through PM ?

I'm from France, i would like to try but i have not been able to find any medical structure performing

this treatment in France or Belgium.

When i asked psychiatrists about it; they pretended not to know anything about it.

I read you're from Germany, maybe you could give me some information ?

Thanks.

[Nick Kyz]

Update:

 

Regarding NRX-1074, the progress is as follows:
the original route (attached) we used did not work out after trying different conditions.

We have designed another route (also attached). We have synthesized compound 8. Two more steps to go until we have the final compound. So we wish to verify the route quickly; secondly, we want to improve the scale-up technology step by step. And we have scaled up production to compound 5. Please take a look at the attached NMR for compound 5 and MS for compound 8.

We are working very hard on this project, as you can see, but there is true difficulty in it. We will come back to you for consult if we have questions. Thank you for your patience.

 

 

https://www.dropbox....RX1074.jpg?dl=0

https://www.dropbox....MRfor5.pdf?dl=0

https://www.dropbox....ound8.docx?dl=0

[Ark]

Update:

Regarding NRX-1074, the progress is as follows:
the original route (attached) we used did not work out after trying different conditions.

We have designed another route (also attached). We have synthesized compound 8. Two more steps to go until we have the final compound. So we wish to verify the route quickly; secondly, we want to improve the scale-up technology step by step. And we have scaled up production to compound 5. Please take a look at the attached NMR for compound 5 and MS for compound 8.

We are working very hard on this project, as you can see, but there is true difficulty in it. We will come back to you for consult if we have questions. Thank you for your patience.

https://www.dropbox....RX1074.jpg?dl=0
https://www.dropbox....MRfor5.pdf?dl=0
https://www.dropbox....ound8.docx?dl=0

Outstanding!


Thanks for your hard work.

[franbird]

Still on track?

[samson75]

Can we expect the delivery on August ?

[Nick Kyz]

On track. I'll ask them their ETA. 

[samson75]

What does ETA mean ?

[stillwater]

Estimated Time of Arrival

[samson75]

Thanks.

[Derville]

Any possibilites to still get on board/partake?

[samson75]

If this product works (i hope so) there will be probably another group-buy for much larger quantities.

 

Edited by samson75, 27 July 2016 - 06:27 PM.

[cheezburger]

Any possibilites to still get on board/partake?

 

Interested too

[ThreeKings12341]

Me 2

[Nick Kyz]

We're closed to new buyers but depending on how this goes we could do another synthesis. I received an update last week.

 

Dear Nick,

 

We tried both routes mentioned to you before, but both were stuck in some difficulties and could not go on successfully. We are unable to solve it in a short time. Please take a look at the attached project report.

 

We are terribly sorry about this. As you know, we have done a good amount of work on this project, but it is more difficult than we anticipated.

 

Can you wait any longer? Do you have a deadline?

We could wait longer, but how long are we talking?

We are still working on the solution, but we are not sure how long it will take, as you know this is a technical problem. 

We have searched for related references and routes from the API manufacturer, including similar ones. But they were not reported publicly.We have 3 Ph.D working on this project, and we will continue to work on it. If you have those references, please provide them for us. We have tried many times as you know. But the result was not good. 

 

The project report was just a compilation of the routes of synthesis they tried and lab reports on precursors. I've asked them for a ballpark estimate on how long they'd need to show some progress.

 

Since they didn't fulfill the contract we have two options. We can be refunded and cancel the synthesis, or we can give them additional time. I guaranteed the group buy so nobody has to wait for them to send the money back. I could do it with IRC.Bio funds. 

 

My personal preference would be to keep the project going, but I don't want to bias anyone in either direction.