15 replies to this topic

[tolerant]

So I stumbled across a novel anti-depressant/anxiolytic drug currently in development called Basimglurant, a selective metabotropic glutamate receptor 5 (mGlu5) inhibitor. You can see from the summary that it looks very promising, especially for those of us with anxiety issues, i.e. not plain depression. There is a thread on here about mGlu receptors on longecity which you can read.

 

I have uploaded a paper describing very detailed preclinical studies performed with the drug to here.

 

The best part is that the drug is available to buy at a fairly reasonable price. You can read about the dosages and duration of the Phase 1 human study here. Depending on how you interpret the information, I have calculated that to replicate the study precisely you will need a minimum either 86 or 126 mg of the drug. This comes to about $500, but only about $90 if there were a group buy with at least 10 people.

 

Please respond in the thread with any comments or if you would like to participate in a group buy.

 

[tolerant]

A quote on mGlu5 antagonists from a study found here: http://www.ncbi.nlm....pubmed/15334174

 

The identification of MPEP (2-methyl-6-(phenylethynyl)-pyridine), a highly selective and brain-penetrant mGlu5 receptor antagonist, allowed the exploration of the therapeutic potential of this class of compounds. Subsequent behavior studies revealed that--with the exception of benzodiazepines--mGlu5 receptor antagonists exhibit the widest and most robust anxiolytic activity in preclinical models seen to date. Upcoming clinical studies will soon indicate if the preclinical anxiolytic-like efficacy translates into anxiolytic activity in humans.

 

 

Edited by tolerant, 29 May 2016 - 06:59 AM.

[Daniel Cooper]

Interesting compound.  But I'm not sure why long term use wouldn't upregulate glutamate production and/or glutamate receptor density and thereby induce tolerance. 

 

Over the years I've found that betting against homeostasis to a bet I seldom win.

 

Love to be wrong about this one though.

 

 

[normalizing]

interesting, im curious of when those "group buys" pop up :D

[tolerant]

Interesting compound.  But I'm not sure why long term use wouldn't upregulate glutamate production and/or glutamate receptor density and thereby induce tolerance. 

 

Over the years I've found that betting against homeostasis to a bet I seldom win.

 

Love to be wrong about this one though.

 

Yes, I agree completely. There's no apparent reason why tolerance will not develop to this drug. There are a number of reasons, however, that lead to optimism:

 

1. It is being investigated for treatment-resistant depression, and a tolerance-inducing drug is obviously not a viable option. The company would not be pouring money into it if they thought it would induce tolerance like benzodiazepines. Maybe they know something we don't. Of course it's also a possibility that they haven't yet studied this issue.

 

2. If you look at the graph on pages 223 of the paper I inserted in the original post, the recovery in anhedonia with Basimglurant occurs over a 21 day period and follows roughly the same pattern as fluoxetine. You could argue that recovery with a GABAergic or "antiglutamatergic" drug would be more-or-less immediate and then stay stable or decline as tolerance sets in (at least this is what happens to me). Although, again, I can roughly recall that when I see a graph where benzodiazepines are used, recovery also follows a gradual pattern. 

 

3. I read somewhere that an mglu5 antagonist works by silencing "overexcited" neurons, which arguably represents a return to homeostasis. Again, however, this is how pregabalin is supposed to work, however a lot of people (including myself) develop tolerance to it too fast for it to be a sustainable treatment for anxiety.

[tolerant]

So I purchased 100 mg from the source I mentioned in my original post. They seem to be the only supplier with prices that are not totally ridiculous. I submitted a sample for NMR testing. I am attaching all the documents received from the lab, including 1H spectra, 13C spectra, spectra with comments by the lab, and the report.

 

The conclusion sent via email was as follows: "The 1H and the 13C had the right amount of peaks for the given structure indicating that the sample is in fact basimglurant. With regards to impurities, you may need to tell the supplier to dry the product better – it looks like there is still dichloromethane and diethyl ether in the product from the synthesis. I don’t know what percentage it is or if it is at a safe level to consume – perhaps they can estimate it for you from the chromatography analysis."

 

Unfortunately it seems that basimglurant from this supplier contains impurities. A quick google search reveal that they are toxic. I have no knowledge of what levels of these impurities is acceptable, and I'm out of my depth when it comes to other methods of analysis, like chromotography. 

 

I hope this helps people looking to source this substance.

 

 

Attached Files

•  1H-Basimglurant1.pdf   86.21KB   3 downloads
•  13C-Basimglurant.pdf   400.03KB   2 downloads
•  Basimglurant analysis.docx   28.1KB   3 downloads
•  Basimglurant-1H-13C.pdf   1.24MB   2 downloads

[Oracle Laboratories]

 Iliya,

That is a funny coincidence!  I was just in the process of finishing my reply to you (should have it sent tonight) and noted the same thing.  These are simply solvents that are left over from the synthesis, but according to your 1H results, are in very low concentrations.  If possible, I would lay the material out on a dry paper towel in a cool, dry, dark cabinet for a couple days, stirring around the material (as best you can) periodically.  

Both Dichloromethane and Diethyl ether are volatile solvents and should evaporate off in dry place if the material is spread out fairly readily.  I am still reviewing some figures on on the 1H data that you sent me, and now that you have the 13C data, this will help tremendously, also.  I wouldn't be over-concerned with the levels of these solvent impurities since the concentrations are very low (trace amounts) according to the results that you obtained.  In reality, it is often very difficult (and often nearly impossible) to synthesize a compound at 100% purity, without leaving some material behind that did not react during synthesis.  

​This is why I would have liked to see a Mass Spectrograph and/or UV Spectrograph, as well, to shed a bit more light on the overall purity of the material.  Don't toss it, though, as the impurities can be evaporated off, and occur in such low concentrations anyway (based on the 1H data, whose resolution could be better, but oh well) that I don't see it being a major issue.  Surprisingly enough, I was rather surprised by the quality of the synthesis based on the results that you were provided.

Anyway, I will be able to shed some more light on the quality/purity/identity of the material after I enter the raw data from your results into our software.  All the the functional groups appear to be correct, present, and in the right positions.  I did notice that slight bit of signal interference (likely the impurities) as soon as I looked at the higher-resolution 1H graph, but their spectral abundance (amount present) is pretty low.  (Again, I can shed a bit more light on how much after I run through some figures, and run through the results via my software).

I should be able to reply to your last few messages sometime tonight or tomorrow afternoon.
 

 

-J. Gona

Oracle Laboratories
NeuroPsych Institute
 

[tolerant]

Thanks for your reply. Before I read it, I decided that this substance from this particular vendor is a definite no-no, but  now, in light of what you said, myself, and other people interested in this compound, may reconsider.

 

For the sake of completeness, I also attach with this message the quality report supplied by the vendor. For obvious reasons, I supposed it's not to be trusted in the same manner as the independent reports in my previous message are to be trusted, but maybe it will shed some more light on the impurities.

 

With regards to drying the substance, there is so little of it and I found it so sticky (could this be the result of it not having been dried properly?) and difficult to handle, that I would probably face losing half of it in the process. So I hope those impurities as they are really nothing to worry about, and the substance is good to ingest.

Attached Files

•  Basimglurant -- DC Chemicals QC.PDF   79.04KB   4 downloads

Edited by tolerant, 07 July 2016 - 09:26 PM.

[tolerant]

@Oracle Laboratories: The material was supplied to me in a vial, and after handling it and seeing that it stuck to the scoop, I thought that I might not have dried the scoop thoroughly enough and therefore introduced some moisture into the substance. I therefore decided to place the vial in an airtight bag with the lid open and a desiccant inside (see enclosed photo). Would this have gone some way to drying out the impurities? Is this an alternative way to spreading out the material on a paper towel?

Attached Files

•  basimglurant.jpg   77.83KB   1 downloads

Edited by tolerant, 08 July 2016 - 04:04 AM.

[MoreNowAgain]

I would be interested in a group buy for this compound. As long as we can source a pure product with no harmful contaminents.

[tolerant]

I would be interested in a group buy for this compound. As long as we can source a pure product with no harmful contaminents.

 

The company I sourced the product from has indicated they could do a synthesis of 5 g for $4700 and 10 g for $6000. A 10 g synthesis would bring the price down ten-fold compared to what I bought 100 mg at retail prices. I guess we would need at least 5 people to be interested. I would be one. If someone else is interested, please respond in this thread.

 

The impurities found in my batch were due to insufficient drying and I have already communicated this to the company. Also, according to Oracle Laboratories, who sounds as if he definitely knows what he's talking about, the impurities were at negligible levels.

[BadgerFox]

I'd be interested in this group buy (price depending - how much did you say that was for each individual buyer?). I have OCD and MGluR5 antagonists seem to have been identified as one substance that could potentially help a lot. I know it's wrong to get hopes up too much as this hasn't been sufficiently proven in a human model yet, but I'm interested in experimenting to see IF it's true. I know the recent Basimglurant trial on depression didn't work well, but then again that might've been because depression's a mood disorder and the placebo had a huge effect on the subjects. OCD generally doesn't respond to placebos like that.

 

I'm trying a few other things for my OCD in the meantime, but if you can get a safe Basimglurant batch without contaminants, please count me in. Do PM me if you have further information about this.

 

[2016ftw]

I'd pitch in to be a part of this. I know I'm new but as with others, I have a strong background in biology and chemistry and know what I'm committing to. I'm in. Let's do this.

[Dhkobbh]

Tm

[Furniture]

Hey y'all. Reviving this old thread because there's been developments in the approval process for Basimglurant:

 

According to Noema Pharma's website, the pharmaceutical company developing Basimglurant (+ a few other proprietary drugs like Gemlapodect), Basimglurant is currently in Phase 2 of drug trials for Pain associated with TN (Trigeminal Neuralgia) & Seizures in TSC (Tuberous Sclerosis Complex).

 

https://noemapharma.com/pipeline/

 

And about a year ago, the FDA granted Fast-Track Designation for Basimglurant:

 

https://www.empr.com...inal-neuralgia/

https://www.globenew...-Neuralgia.html

 

 

 

Attached Files

•  Screenshot 2023-11-17 at 2.08.11 PM.png   417.42KB   0 downloads

Edited by Furniture, 17 November 2023 - 10:10 PM.

[Daniel Cooper]

Hey y'all. Reviving this old thread because there's been developments in the approval process for Basimglurant:

 

According to Noema Pharma's website, the pharmaceutical company developing Basimglurant (+ a few other proprietary drugs like Gemlapodect), Basimglurant is currently in Phase 2 of drug trials for Pain associated with TN (Trigeminal Neuralgia) & Seizures in TSC (Tuberous Sclerosis Complex).

 

https://noemapharma.com/pipeline/

 

And about a year ago, the FDA granted Fast-Track Designation for Basimglurant:

 

https://www.empr.com...inal-neuralgia/

 

Thanks for the update. Interesting compound.