659 replies to this topic

[Reformed-Redan]

I want to see if there is any new information on NRX-1074 an orally bio-available, potent (thousands more potent than GLYX-13), and simpler structure (non peptide). I won't be handling this group buy as there are too many variables and I don't have the time nor desire to head it. Though I'd love to participate in a future group buy for this compound. So, any news much much appreciated. Thanks.

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

Edited by yadayada, 04 April 2014 - 04:29 PM.

[formergenius]

Unfortunately, despite having searched for it several times, I haven't found any updates this year. It seems Naurex has chosen to be secretive about it, which is a shame considering they're also developing NR2A subunit specific ligands (which currently don't exist). I suppose they will handle it in a similar manner. That said, if it still becomes available, I'm in.

Still haven't finished my GLYX-13 due to ear problems confounding variables. Looks like it'll take another 3-4 weeks before I know more, and until then I'm not taking anything NMDAergic.

[Virtual Reality]

Yeah im wondering when more information will be released about nrx-1074 aswel. There are recruiting patients for a clinical trial starting in april.
Im wondering how the procedure goes about releasing information about the compound, they may keep it for themself, but are they even allowed by law etc.?

[VERITAS INCORRUPTUS]

They will keep this well hidden for as long as possible methinks.
Though if someone really digs into the Naurex patent portfolio there might be something that stands out

The Randomized, Double-Blind, Placebo-Controlled Single Intravenous and Oral Ascending Dose Study of the Safety, Tolerability and Pharmacokinetics of NRX-1074 in Normal Healthy Volunteers will be assaying oral doses of 25mg and 125mg. Intravenous will be tested at 1mg - 50mg

Assumably they anticipate effective dosages to be within this range.

Just what structure they derived from the tetrapeptide GLYX platform will be interesting to see when it is finally revealed.

Edited by VERITAS INCORRUPTUS, 07 April 2014 - 04:34 PM.

[EncyclopediaBrown]

Unfortunately, despite having searched for it several times, I haven't found any updates this year. It seems Naurex has chosen to be secretive about it, which is a shame considering they're also developing NR2A subunit specific ligands (which currently don't exist). I suppose they will handle it in a similar manner. That said, if it still becomes available, I'm in.

Still haven't finished my GLYX-13 due to ear problems confounding variables. Looks like it'll take another 3-4 weeks before I know more, and until then I'm not taking anything NMDAergic.

Can you let us know where you purchased GLYX-13?

[Virtual Reality]

They will keep this well hidden for as long as possible methinks.
Though if someone really digs into the Naurex patent portfolio there might be something that stands out

The Randomized, Double-Blind, Placebo-Controlled Single Intravenous and Oral Ascending Dose Study of the Safety, Tolerability and Pharmacokinetics of NRX-1074 in Normal Healthy Volunteers will be assaying oral doses of 25mg and 125mg. Intravenous will be tested at 1mg - 50mg

Assumably they anticipate effective dosages to be within this range.

Just what structure they derived from the tetrapeptide GLYX platform will be interesting to see when it is finally revealed.

 

 

Hmm tried searching through google patents , if thats what you mean, but didnt come up with the information we are looking for. Were you able to find it?

[typ3z3r0]

I've found a promising substitute to NRX-1074 for now, and posted some info about it here.

Edited by typ3z3r0, 15 April 2014 - 01:37 AM.

[FeelsNumbMan]

Thanks for that. Unfortunately, when the hell are any of these things gonna be available for purchase?! I know being patience is one thing but when you're suffering from depression and the feeling of not wanting to do anything, nothing meaning anything, and just trying to keep your mind busy until the day is over (and the exact same thing happens every day) -- how can I just stand waiting?

 

I just want something promising for us to have. Something that actually works for those who are depressed. And not something that costs a shitload of money either because it's a cycle of what a depressed person cannot really seem to do.

[Metagene]

Thanks for that. Unfortunately, when the hell are any of these things gonna be available for purchase?! I know being patience is one thing but when you're suffering from depression and the feeling of not wanting to do anything, nothing meaning anything, and just trying to keep your mind busy until the day is over (and the exact same thing happens every day) -- how can I just stand waiting?

 

I just want something promising for us to have. Something that actually works for those who are depressed. And not something that costs a shitload of money either because it's a cycle of what a depressed person cannot really seem to do.

 

Can't be long now, Naurex started phase 2 trials for NRX-1074 in major depressive disorder.

 

http://www.fiercebio...depressant-glyx

[formergenius]

Do we know when GLYX-13's structure was released relative to which trial phase? That might provide some guesstimation to when NRX-1074's structure will be available.

FeelsNumbMan, if it's of any consolation, I'm in the same position as you.

[typ3z3r0]

Unfortunately, interest in the two orally active antagonists of the NMDA receptor subunit 2B for which the structures are known - CERC-301 and  EVT 101 - is really low at this point, so it's highly unlikely that a nootropics company or an individual will have either synthesised. I guess we just have to wait to get the structure of NRX-1074.   

Edited by typ3z3r0, 10 May 2014 - 02:00 AM.

[datrat]

Unfortunately, interest in the two orally active antagonists of the NMDA receptor subunit 2B for which the structures are known - CERC-301 and  EVT 101 - is really low at this point, so it's highly unlikely that a nootropics company or an individual will have either synthesised. I guess we just have to wait to get the structure of NRX-1074.   

 

When you say interest, are you referring to the usual suspects like us - longecity frequenters having low interest. Do you think either one is feasible to have synthesized ? I would be very interested in trying either one if we could get them.

[ILIkeBeer]

Boy howdie would I love to give this a try... I am definitively in for a group buy if it becomes available.

[Milkyway]

Please contact me if a group buy does become available for NRX 1074 should the structure be disclosed.

[Reformed-Redan]

Untile the structure of NRX-1074 is found we should focus on MI-4

"MI-4

The latest hope as a psychiatric rescue drug is called MI-4, and news of its promise was reported earlier this week at the 
San Diego meeting of the Federation of American Societies for Experimental Biology (FASEB). Scientists also have 
identified the drug as Ro-25-6981.

In the test tube, MI-4 was found to simultaneously increase the availability in the brain of three neurotransmitters that
play a key role in depression: serotonin, dopamine and norepinephrine. Researchers led by Jeffery N. Talbot of Roseman 
University of Health Science in Henderson, Nev., found that in mice that had been stressed and trained to expect no rescue 
from frightening circumstances -- a depression-like condition called "learned helplessness" -- MI-4 quickly restored more 
hopeful behavior and continued to do so for three weeks -- a lengthy stretch for a mouse.

Compared with a placebo medication, MI-4 made virtual social butterflies of mice who had been brought low by social defeat,
and whose depression manifested as withdrawal. And for a continuous three-week period, it helped fortify those mice against 
the soul-crushing effects of further social defeat.

MI-4 appears to have several advantages over ketamine, which, as a drug that induces a sort of out-of-body high when used at 
higher doses and is, therefore, considered to have abuse potential. Mice taking MI-4 were no more likely to hang out close to
the drug-dispenser than they were to wander around and explore and socialize -- a clear sign that its abuse or addictive 
potential is low."

and

"

Ro 25-6981, a highly potent and selective blocker of N-methyl-D-aspartate receptors containing the NR2B subunit. Characterization in vitro.

Fischer G¹, Mutel V, Trube G, Malherbe P, Kew JN, Mohacsi E, Heitz MP, Kemp JA.

Author information

Abstract

The interaction of Ro 25-6981 with N-methyl-D-aspartate (NMDA) receptors was characterized by a variety of different tests in vitro. Ro 25-6981 inhibited 3H-MK-801 binding to rat forebrain membranes in a biphasic manner with IC50 values of 0.003 microM and 149 microM for high- (about 60%) and low-affinity sites, respectively. NMDA receptor subtypes expressed in Xenopus oocytes were blocked with IC50 values of 0.009 microM and 52 microM for the subunit combinations NR1C & NR2B and NR1C & NR2A, respectively, which indicated a >5000-fold selectivity. Like ifenprodil, Ro 25-6981 blocked NMDA receptor subtypes in an activity-dependent manner. Ro 25-6981 protected cultured cortical neurons against glutamate toxicity (16 h exposure to 300 microM glutamate) and combined oxygen and glucose deprivation (60 min followed by 20 h recovery) with IC50 values of 0.4 microM and 0.04 microM, respectively. Ro 25-6981 was more potent than ifenprodil in all of these tests. It showed no protection against kainate toxicity (exposure to 500 microM for 20 h) and only weak activity in blocking Na+ and Ca++ channels, activated by exposure of cortical neurons to veratridine (10 microM) and potassium (50 mM), respectively. These findings demonstrate that Ro 25-6981 is a highly selective, activity-dependent blocker of NMDA receptors that contain the NR2B subunit."

 

[PWAIN]

Would we need Ro-25-6981 maleate salt or the Ro-25-6981 hydrochloride hydrate or something else? Also, any ideas on the dose, lots of references to microM's but don't know what that translates to in the real world?

 

We have the formula and pics of the molecule for this one at least (From Sigma Aldrich).

 

[R-(R*,S*)]-α-(4-Hydroxyphenyl)-β-methyl-4-(phenylmethyl)-1-piperidinepropanol hydrochloride hydrate   (C₂₂H₂₉NO₂ · HCl · xH₂O)

 

1-Piperidinepropanol, α-(4-hydroxyphenyl)-β-methyl-4-(phenylmethyl)-, ( αR,βS)-, (2Z)-2-butenedioate (1:1), [R-(R*,S*)]-α-(4-Hydroxyphenyl)-β-methyl-4-(phenylmethyl)-1-piperidinepropanol maleate salt    (C₂₂H₂₉NO₂ · C₄H₄O₄ )

 

 

http://www.sigmaaldr...ng=en&region=AU

 

http://www.sigmaaldr...ng=en&region=AU

 

[ILIkeBeer]

This would be great to try but I am not sure they have done any human trials yet... as to safety and dose etc.

[Virtual Reality]

http://naurex.com/wp...05.15-FINAL.pdf

Might be worth checking out, if someone lives close.

Edited by alex921, 16 May 2014 - 10:30 AM.

[Milkyway]

So is no one interested in CERC 301?  It seems like it might be worth a try, a group buy?  Maybe when T.H.T. is up and running they might be persuaded to synthesize it.  I know it is not the thing we have been waiting so long for "NRX 1074" or has it gained the same fanfare but it seems like it might be worth trying while we are waiting.

 

"It tastes like licorice."

"That's the way with everything."

"Especially everything you ever waited so long for like absinthe."

 

--Hemingway, " Hills Like White Elephants"

[Reformed-Redan]

Looking into Ro-25-6981 and CERC 301 currently. Think either one with the former in mind has a good chance of getting into the market. 

[Milkyway]

They both seem like they might be helpful except no one knows what is a proper dosage range for the Ro-25-6981.  Also, does anyone have any idea or any way of predicting when NRX 1074's chemical structure will be revealed?  As much as I hate the idea of running to a chemical fix to treat psychological problems as that seems to be what landed me here in the first place this is far more anxiety than I feel like dealing with and I need relief before I start screaming!

[tolerant]

I am in for this group buy.

[Reformed-Redan]

From everything I gather, Ro-25-6981 is the one to go with and will most likely become available in the near future from THT. Just need some time to get other project outta the way. 

[Milkyway]

Are you pretty sure Ro-25-6981 will become available soon?

[MasterHerb]

Do not do business with yadayada......he is a fraud. See:

 

http://www.longecity...roup-buy/page-9

[Reformed-Redan]

Do not do business with yadayada......he is a fraud. See:

 

http://www.longecity...roup-buy/page-9

I already offered you a refund in the ISRIB group buy thread. So, take it or leave it, I guess. 

Anyway, I'm moving over to reedit nootropics. 

Edited by yadayada, 17 June 2014 - 11:19 AM.

[Metagene]

Here is the most recent patent http://www.google.co...ents/US8673843

IIRC this was posted in the pervious thread http://www.google.co...2542254A1?cl=en


"peptide mimetic" heh.

Edited by Metagene, 18 July 2014 - 11:20 PM.

[typ3z3r0]

NRX-1074 isn't in there either unfortunately.

Neu2000 (2-hydroxy-5-(2,3,5,6-tetrafluoro-4-trifluoromethyl-benzylamino)-benzoic acid) seems pretty interesting, seeing as it's a selective antagonist of NR2B like CERC-301,  EVT 101 and  EVT 103, however is also a radical scavenger/spin-trapping molecule. AAD-2004, also in GNT Pharma's pipeline, looks interesting and shows promise for depression relief.

[Virtual Reality]

http://en.wikipedia.org/wiki/NRX-1074

Unfortanetly, no structure yet.

[Milkyway]

Does anyone have any idea why it is taking so long for the structure to be disclosed?  And once it is can anyone anticipate how long it wil take before we are able to actually obtain it through a group buy?  Just wondered if anyone could even speculate on these things.