11 replies to this topic

[FuzzMunky]

Paraphrasing from information across the web -

 

4-Chlorokynurenine or AV-101 is a promising NMDA antagonist prodrug undergoing NIMH sponsored Phase IIa trials at the moment. It is being investigated by Dr. Carlos A. Zarate, one of the nations leading experts in Depression. In addition, Phase IIb trials are about to begin alongside this, also sponsored by the NIMH.

 

The mechanism of action is similar to Rapastinel (GLYX-13), but orally available and a full antagonist of the GluN1 subunit, as opposed to the partial antagonism of GLYX-13. It is also considered more potent and with a better half-life profile. So, it is more similar to NRX-1074, only it is further along in the clinical trials.

 

I am wondering why this chemical is getting no attention on this forum, nor Reddit, while research chemicals like NSI-189 get almost 200 pages of a thread and the other popular NMDA antagonist compounds (eg. NRX-1074) are getting reverse engineered at great cost? As I understand it, from an archived Reddit thread, (the only mention on Reddit of this compound), MisterCeretropic said it is a much simpler compound to synthesise than NRX-1074. Yet I do not see any serious discussion of it like I do with some of the aforementioned compounds.

 

Anyone got any insider info on this? Or any updates that I am unaware of that would reduce it's appeal to this community?

[FuzzMunky]

Or just general discussion? The silence is, frankly, weird.

[Der Springende Punkt]

Thanks for posting, FuzzMunky. I fully second your questions. As I remember correctly Ceretropic do not want to offer this compound due to patent restrictions but since it is much easier to synthesise a successful group buy would be more likely than for NRX-1074. If only the attraction would be much higher...

[PeaceAndProsperity]

I would be scared about the neurotoxicity, if it is a prodrug. Also scared about potentially causing psychosis.

[FuzzMunky]

I would be scared about the neurotoxicity, if it is a prodrug. Also scared about potentially causing psychosis.

Here's an excerpt from a study I found, looking into the neuroprotective and neurotoxic effects of the different kynurenines. Here it was deemed to have neuroprotective agency.

"Halogenated KYNA analogues have also been tested; 7-chlorokynurenic acid is a selective antagonist of the glycine site of NMDA receptors [141], and it was able to modulate kainate-induced neurodegenerative changes [142,143]. However, the blood-brain barrier permeability of this drug is not optimal; therefore, its prodrug, 4-chlorokynurenine (also known as AV-101), was examined and has been shown to be protective against QUIN neurotoxicity [143]. AV-101 has successfully completed a phase I clinical trial for the evaluation of safety, tolerability and pharmacokinetic profile (ClinicalTrials.gov Identifier: NCT01483846) and hopefully will be further processed."
https://www.ncbi.nlm...les/PMC4463617/

Also concerning safety, since the substance is long past phase 1 development:
"The primary safety and tolerability endpoints of the Phase 1 program were met. This is a very safe compound with no observed side effects," commented Mark S. Wallace, MD, Chair of the Division of Pain Medicine, Department of Anesthesiology at UCSD and the principal investigator of the study.

Why should a prodrug, where a lot is known about its mechanism of action, be suspect, yet something like NSI-189; where literally nothing concrete about how it acts is known or at least shared, is considered safe to order in and self medicate with?

Edited by FuzzMunky, 07 March 2017 - 08:13 PM.

[PeaceAndProsperity]

 

I would be scared about the neurotoxicity, if it is a prodrug. Also scared about potentially causing psychosis.

Here's an excerpt from a study I found, looking into the neuroprotective and neurotoxic effects of the different kynurenines. Here it was deemed to have neuroprotective agency.

"Halogenated KYNA analogues have also been tested; 7-chlorokynurenic acid is a selective antagonist of the glycine site of NMDA receptors [141], and it was able to modulate kainate-induced neurodegenerative changes [142,143]. However, the blood-brain barrier permeability of this drug is not optimal; therefore, its prodrug, 4-chlorokynurenine (also known as AV-101), was examined and has been shown to be protective against QUIN neurotoxicity [143]. AV-101 has successfully completed a phase I clinical trial for the evaluation of safety, tolerability and pharmacokinetic profile (ClinicalTrials.gov Identifier: NCT01483846) and hopefully will be further processed."
https://www.ncbi.nlm...les/PMC4463617/

Also concerning safety, since the substance is long past phase 1 development:
"The primary safety and tolerability endpoints of the Phase 1 program were met. This is a very safe compound with no observed side effects," commented Mark S. Wallace, MD, Chair of the Division of Pain Medicine, Department of Anesthesiology at UCSD and the principal investigator of the study.

Why should a prodrug, where a lot is known about its mechanism of action, be suspect, yet something like NSI-189; where literally nothing concrete about how it acts is known or at least shared, is considered safe to order in and self medicate with?

 

I guess I falsely assumed that all the NMDA antagonist tryptophan-metabolites were one chemical

 

[franbird]

What would group buy cost be?

[Clement Ehling]

I guess its good stuff to prevent tolerance or addiction ?

How it compare to memantine ? 

Thanks

[Irishdude]

I'd be up for this if others can lead.

[FuzzMunky]

I have no idea about group buy costs. I thought other people with more knowledge in that department would be interested, seeing as they went to such great lengths over the impossibly difficult NRX-1074 group buy.

[VitD_1]

Did anything happen with this?

[Mind_Paralysis]

 

 

I would be scared about the neurotoxicity, if it is a prodrug. Also scared about potentially causing psychosis.

Here's an excerpt from a study I found, looking into the neuroprotective and neurotoxic effects of the different kynurenines. Here it was deemed to have neuroprotective agency.

"Halogenated KYNA analogues have also been tested; 7-chlorokynurenic acid is a selective antagonist of the glycine site of NMDA receptors [141], and it was able to modulate kainate-induced neurodegenerative changes [142,143]. However, the blood-brain barrier permeability of this drug is not optimal; therefore, its prodrug, 4-chlorokynurenine (also known as AV-101), was examined and has been shown to be protective against QUIN neurotoxicity [143]. AV-101 has successfully completed a phase I clinical trial for the evaluation of safety, tolerability and pharmacokinetic profile (ClinicalTrials.gov Identifier: NCT01483846) and hopefully will be further processed."
https://www.ncbi.nlm...les/PMC4463617/

Also concerning safety, since the substance is long past phase 1 development:
"The primary safety and tolerability endpoints of the Phase 1 program were met. This is a very safe compound with no observed side effects," commented Mark S. Wallace, MD, Chair of the Division of Pain Medicine, Department of Anesthesiology at UCSD and the principal investigator of the study.

Why should a prodrug, where a lot is known about its mechanism of action, be suspect, yet something like NSI-189; where literally nothing concrete about how it acts is known or at least shared, is considered safe to order in and self medicate with?

 

I guess I falsely assumed that all the NMDA antagonist tryptophan-metabolites were one chemical

 

 

 

I did the same at first, actually - HOWever... since Kynurenic Acid, a closely related chemical, and NMDA-antagonist, have been linked to psychosis, then YES, people with such issues should probably stay away from this drug as well.

 

HOWever... again... some of us are born with ADHD and similar disorders, or Autism, which has shown severe SUB-activity in the NMDA-networks - for us, this drug could be very useful. But we are, obviously, a completely different patient-group then people susceptible to psychosis or whom have some form of Schizophrenia-spectrum disorder.