3 votes
Posted 30 April 2017 - 08:18 AM
People paying a sum proportionate to what they have ordered in drug-amounts for the NMR-testing seems like the reasonable way to go - although yes, somewhat more complicated.
Well, all I know is that I'm definitively prepared to pay for getting NMR-testing done! = ) That's the gold-standard when it comes to stuff like this, research-chemicals.
Posted 14 May 2017 - 10:04 AM
Hey I have been on holidays haha. Anyway I can't see what is the situation now with the group buy and having it tested independently before it is ready to be distributed.
Are we closer to getting the final product?
That is a great read btw, brighterpath!
Posted 15 May 2017 - 02:30 PM
Hey I have been on holidays haha. Anyway I can't see what is the situation now with the group buy and having it tested independently before it is ready to be distributed.
Are we closer to getting the final product?
The lab has been waiting on test results and purifying the compound, etc. They were supposed to ship out 2 weeks ago, but the HPLC testing hadn't come back, and later they found out that the purity was only 96%, so they took a few more days to purify the compound up to 99%. They are now waiting for the chiral HPLC testing, and they are hoping it will be done in a few days. I am hoping we could get the compound by the end of the week.
The price per 100mg has changed, a bit higher than before, so I will be reaching out to individuals and settling accounts.
Edited by brighterpath, 15 May 2017 - 02:31 PM.
Posted 18 May 2017 - 06:16 AM
Btw... I just got to thinking about up and down -regulation - CERC-501 is probably a drug that needs to be tapered off a bit! We can't afford to be hit with a sudden UPregulation of the kappa-receptors, dude...! o.O Could be down-right catastrophic!
So everyone, when you have your dose, plan out how you're going to use it - make sure that you have a certain amount left towards the end of your trial, to properly taper it down.
I think what Stink is saying here is EXTREMELY important. There is evidence from Salvia users posting on these forums that kappa opioid receptors downregulate very quickly, in a matter of 24 hours or less. I don't want to be a party pooper, and I hope CERC-501 is a long-term solution, but you have to start with the assumption that in response to CERC-501 the kappa opioid receptors will similarly begin to upregulate very quickly. That means that you may be hit with a withdrawal syndrome upon discontinuation where your symptoms become worse than they were when you started CERC-501.
Posted 19 May 2017 - 04:42 AM
Hey everyone,
I got the news from the lab last night that all of the testing is finally complete, and the compound is ready for shipping. I'm sorry about the weeks of delays. The lab kept having to repurify the compound and retest the compound, but from the results they have sent me, we have a 99+% pure product.
I will let you know when it finally gets here. Hopefully it will be by Monday or Tuesday at the latest. Once I have it, the compound will be shipped for NMR testing immediately for verification, and I will send them out to you at the same time.
If you have not done so, please send me your shipping address, and the exact amount of the compound you want given the new pricing (http://www.longecity...e-4#entry813886)
Let me know if you have any questions or concerns,
Brighter
Posted 03 June 2017 - 02:27 AM
The NMR result came back from the U.S. lab yesterday, and they confirmed that we have the right compound. The material we have is about 95% pure CERC-501. They could not identify the impurities, but it is possible that I accidentally introduced some impurities in handling since I'm not in a sterile environment. I will pursue the case with them to see if I can figure it out. Several of us have been taking the compound for the past week with no ill effect, so it seems safe, at least in the short term.
There are a few things I would like to note. I think it is possible that the compound needs to be used with a solvent. Some drugs are not absorbed easily in it's freebase form, so when they are sold as medication they are sold in the salt form. We however have a freebase compound in our hands. During my experimentations, I found that if I put the compound under my tongue, it turned into a solid ball and would not dissolve. I tried dissolving it into water, which didn't work. I tried dissolving it into ethanol, which didn't work. Then I tried dissolving it into oil, which also didn't work.
I ended up using DMSO as a solvent, and the compound dissolved well. I use just a few drops, dissolve the compound then mix it with juice to take it orally. I believe this makes the drug work better, or might even be a necessity for any absorption.
Posted 03 June 2017 - 09:03 AM
The NMR result came back from the U.S. lab yesterday, and they confirmed that we have the right compound. The material we have is about 95% pure CERC-501. They could not identify the impurities, but it is possible that I accidentally introduced some impurities in handling since I'm not in a sterile environment. I will pursue the case with them to see if I can figure it out. Several of us have been taking the compound for the past week with no ill effect, so it seems safe, at least in the short term.
There are a few things I would like to note. I think it is possible that the compound needs to be used with a solvent. Some drugs are not absorbed easily in it's freebase form, so when they are sold as medication they are sold in the salt form. We however have a freebase compound in our hands. During my experimentations, I found that if I put the compound under my tongue, it turned into a solid ball and would not dissolve. I tried dissolving it into water, which didn't work. I tried dissolving it into ethanol, which didn't work. Then I tried dissolving it into oil, which also didn't work.
I ended up using DMSO as a solvent, and the compound dissolved well. I use just a few drops, dissolve the compound then mix it with juice to take it orally. I believe this makes the drug work better, or might even be a necessity for any absorption.
All right, sounds fairly good! = ) 95% is cutting it a little bit close though... 97-98% would have been ideal. If they can't identify the impurities I take it that it's not something serious such as heavy metals or known toxins though, yes?
Could you by chance message me the lab-reports, both from the synthesisers and the NMR-data? I'd love to have a look at it myself.
VERY interesting note about the solubility of this stuff btw! I hadn't thought about that at all! Do we know what form of the salt they're using in the studies? I seem to have missed that info in the reports. Would of course be a valuable improvement for any future group buys.
God damnit btw, this means I have to source some good DMSO too...! Oh well, I was looking into it for exercise-recuperation anyway.
EDIT:
Btw, what dosing are you using? 10 mg? Not sure what the dosage should be on this stuff - it's not entirely clear from the studies - the animal tests used 10 mg /kilo, which would then need to be converted to human dosing - often the rodents use many times higher dosages of compounds then humans, because of their higher metabolic rate.
So, anybody up for making the conversion-calculation?
It might just be that 10 mg is too low of a dose - might be that 30 mg is a more comparable rat-human dosage.
And finally... have you noticed ANY effects from the drug yet?? Like, any at all? After a few days Placebo should be next to nothing, so I'm curious to see if you've started noticing it. In theory it could be very discreet... perhaps something that's only noticeable if one exposes ones self to stressful situations, like a school-test or something like that.
Edited by Stinkorninjor, 03 June 2017 - 09:58 AM.
Posted 03 June 2017 - 04:41 PM
I am HIGHLY concerned about the purity issues especially with respect to the DMSO. I think someone with more background in chemistry and biochem than I needs to look very closely at the specific impurities detected and how DMSO interacts with them. DMSO gets things into cells incredibly fast. If you took it undiluted with water, say the cerc just in DMSO dropped in your mouth or on your tongue, it would be in your bloodstream before it left your mouth/throat. DMSO carries EVERYTHING, and can make toxins and poisons orders of magnitude more potent.
I will not be experimenting with this in DMSO until we can fully assess safety.
Posted 03 June 2017 - 08:43 PM
I am HIGHLY concerned about the purity issues especially with respect to the DMSO. I think someone with more background in chemistry and biochem than I needs to look very closely at the specific impurities detected and how DMSO interacts with them. DMSO gets things into cells incredibly fast. If you took it undiluted with water, say the cerc just in DMSO dropped in your mouth or on your tongue, it would be in your bloodstream before it left your mouth/throat. DMSO carries EVERYTHING, and can make toxins and poisons orders of magnitude more potent.
I will not be experimenting with this in DMSO until we can fully assess safety.
Hmm, yes, you bring up a very good point here... DMSO is a bit of an issue, what with how it breaches cell-membranes - just read up more on it, and the regular chemists are as I understand it, quite skeptical towards cavalier use of it.
Anyways - what ELSE could we by chance use to dissolve CERC-501? Apparently oil failed - but there should be SOMETHING other than DMSO! Can we get a chemist in here, and have a look at the structure of CERC-501? By comparing it towards compounds with a similar structure, but with known solubility-data, we might be able to figure out a replacement for DMSO.
Let's see... what is the solubility-profile of other opiate-antagonists for instance? Perhaps citric acid could work... perhaps if it's given some time to dissolve it, yes? A few hours or so, by chance?
Posted 07 June 2017 - 04:10 AM
The impurities have been identified, and it's t-butyl methyl ether. You can do your own research on it if you'd like, but the health effects of it at low doses are debated. It is on the one hand notorious for making tap water undrinkable, but my understanding is that this is due to the fact that it has an extremely strong oder, making drinking unpleasant, not because it is extremely dangerous. On the other hand it seems to be used in at least one surgical method to dissolve gallstones and injected directly into the body, so it's definitely not something that's going to kill you right away. I've been taking the compound with DMSO in the past 2 weeks with no noticeable ill effects.
However it is definitely something we should seek to minimize. The boiling point of t-butyl methyl ether is only 131.4°F (55.2°C). I'm trying to find out whether it is possible to heat up cerc501 to this temperature without compromising it's structure to just evaporate any impurities we have. Let me know if anyone finds suitable solutions. I'll be doing research and will keep you updated as I find out more.
Edited by brighterpath, 07 June 2017 - 04:10 AM.
Posted 07 June 2017 - 11:21 AM
The impurities have been identified, and it's t-butyl methyl ether. You can do your own research on it if you'd like, but the health effects of it at low doses are debated. It is on the one hand notorious for making tap water undrinkable, but my understanding is that this is due to the fact that it has an extremely strong odor, making drinking unpleasant, not because it is extremely dangerous. On the other hand it seems to be used in at least one surgical method to dissolve gallstones and injected directly into the body, so it's definitely not something that's going to kill you right away. I've been taking the compound with DMSO in the past 2 weeks with no noticeable ill effects.
However it is definitely something we should seek to minimize. The boiling point of t-butyl methyl ether is only 131.4°F (55.2°C). I'm trying to find out whether it is possible to heat up cerc501 to this temperature without compromising it's structure to just evaporate any impurities we have. Let me know if anyone finds suitable solutions. I'll be doing research and will keep you updated as I find out more.
HMM!
Unpleasant news - but not as bad as it could be - it's certainly not mercury or lead, at least. I've been reading up on it, and there does seem to be some slight evidence pointing towards carcinogenicity, but it's hard to tell if it has any tangible such effects, at low doses.
Still, I imagine if one wants to be safe, then ingest it with a healthy dose of anti-carcinogenic supplements, Vitamin C in high doses is one such compound, I believe.
Let us know if you find any data on the boiling point of cerc-501 - a fairly clever idea that, to potentially boil that MTBE sh*t away. Has the manufacturer replied to your enquiry into how the MTBE enters the process? Could we eliminate it if the synthesis process is altered for a future group buy?
Hey... I just got an idea! We might not have to boil or heat this AT ALL above room-temperature! Because MTBE actually appears to have fairly good solubility in water! And when you describe the characteristics of the majority of the mass in the synthesized compound, you mention how the solubility is god-awful! So if I'm reading this data correct...
42 g/L (20 °C)[1]
Link:
http://gestis-en.itr...default.htm$3.0
Then this stuff starts dissolving into water fairly quickly! That's why it's a problem when it leaks from storage tanks of gasoline - the MTBE is one of the first compounds to dissolve into ground water.
In theory... we would just have to put the compound in a container of water, perhaps for 2-3 days, in room-temperature, and then remove the liquid with a thin siphon, or a filter of some sort, and the CERC-501 will clump in the filter, while the dissolved MTBE will go down the drain! = )
Except... I'm not in favour of putting MTBE in the drain... so let the liquid go into another container, then have the water vaporize, and then throw that MTBE container in the hazardous materials section of your local recycling-centre.
Edited by Stinkorninjor, 07 June 2017 - 11:24 AM.
Posted 10 June 2017 - 02:52 AM
The lab has gotten back to me and suggested vacuum drying the compound at 40-50 degrees celcius overnight. They said the compound is stable. I actually just put a few dose's worth of it into a tabletop oven at "warm" setting for maybe 10 minutes, and it got rid of the "gasoline" taste/smell from the compound, so I think it worked.
I tried Stink's method of using water but it was hard to get the little flakes of the powder back together.
Posted 11 June 2017 - 05:49 AM
The lab has gotten back to me and suggested vacuum drying the compound at 40-50 degrees celcius overnight. They said the compound is stable. I actually just put a few dose's worth of it into a tabletop oven at "warm" setting for maybe 10 minutes, and it got rid of the "gasoline" taste/smell from the compound, so I think it worked.
I tried Stink's method of using water but it was hard to get the little flakes of the powder back together.
And where are we supposed to get vacuum drying equipment? When I ordered Basimglurant from them, the testing lab said they don't dry their product enough and they've just done the same thing again.
Would it be safe to put the stuff in an oven while it's still in the plastic vial? Seeing that the melting point of plastic is about 100 degrees Celsius.
Edited by tolerant, 11 June 2017 - 05:51 AM.
Posted 11 June 2017 - 11:22 AM
OK, a quick lookup suggests vacuum drying seems to be a low temperature drying method, used specifically when ordinary drying via high temperature is not possible. So they are basically saying "don't heat it". Couple that with their storage instructions of "-20 Celsius". I don't think they necessarily have much of a clue with regards to the temperature that would compromise CERC-501.
Edited by tolerant, 11 June 2017 - 11:24 AM.
Posted 11 June 2017 - 03:09 PM
OK, a quick lookup suggests vacuum drying seems to be a low temperature drying method, used specifically when ordinary drying via high temperature is not possible. So they are basically saying "don't heat it". Couple that with their storage instructions of "-20 Celsius". I don't think they necessarily have much of a clue with regards to the temperature that would compromise CERC-501.
Hmm... but can WE figure it out? Can we have a look at the chemical structure of CERC-501 and compare it with its closest molecular relative, to see if their is thermostability-data available on that compound? That should at least give us some reasonable ideas about this stuff.
Man...! How is it that none of thought about this before?? Oh well - we're all new to the group buy thing, really.
Hmm... perhaps we could ask the owner of Ceretropic? He's quite knowledgable, and has fellow chemists in-house to ask as well... Maybe he could have a look at the compound, and give us his best ideas?
I'm sitting here and comparing CERC-501 to the older JDTic, and it's surprisingly different - but there are also clear similarities - it's got a system of hydrogen-rings, almost like a tri-cyclic, but separated from each other, like in a chain. Hmm... I need to learn more chemistry!
The molar mass is similar between the two compounds... CERC-501 appears to be slightly lighter than JDtic tho'.
Let's see... Alvimopan, which is apparently the most closely related in-use, well-studied drug, to JDtic, also has a similar molar mass! Ok, this is promising... : ) Perhaps we can look at Alvimopan and find its thermostability-data, to see how stable it is, and then make an informed guess about the properties of CERC-501?
https://en.wikipedia.../wiki/Alvimopan
Here's a book which attempts to teach the basics of such knowledge, of interpreting the stability of various chemical structures - perhaps some of you can read the excerpts and figure this out? I would do it myself, but my motivation can only stretch for so far.
Reactive Intermediate Chemistry - page 729
https://books.google...ompound&f=false
Posted 11 June 2017 - 06:26 PM
Tolerent, I think -20 celcius storage instructions is pretty standard on a myriad of compounds to definitely keep them from degrading long term, so I don't think this is compound specific. And the vaccum drying was a suggestion to aid the evaporation process (she suggested vaccum drying at 50 to 60 degrees which is already the regular boiling point), but from my experience it is fine to put the compound in a glass vial and monitor it closely in a regular convection oven at low temperatures. My oven's warm setting barely goes over 60 degrees celcius, or less than 100 degrees fahrenheit.
Another option would be trying to heat up water, then keeping your vial dipped in hot water for a while to heat up the glass.
Posted 12 June 2017 - 04:33 AM
Yes, I realise that about the "-20 Celsius" storage instructions. I think the same instructions came when they supplied basimglurant. I stand corrected on the vacuum drying. I missed the point that they recommended vacuum drying at 40-50 Celsius.
Edited by tolerant, 12 June 2017 - 04:36 AM.
Posted 12 June 2017 - 02:23 PM
I have received my CERC-501 today as well!
It is also yellow and somewhat lumpy - this is most likely as a result of the impurities, because as I understand it, according to the data, it's supposed to be a odourless, colourless substance.
Right, now I need to buy some caps, so I can cap it. Might have to wait with using it as well, since I figure I'm going to combine it with NSI-189, in order to get a double-whammy of good experiences and good memories to then cherish for the rest of life.
I'm thinking about putting water inside of it, and then let it soak for about two hours, and then dry it in the oven at 50-60 degrees.
Has ANYONE looked closer at my last post? I'm too brainfogged and smashed to make it out, but as far as I could tell, it should be possible to determine CERC-501's thermostability by comparing it to other, similar compounds.
At the very least we know that the impurity is very, very unstable, and seems to dissipate in water fairly quickly. Which is definitively different from actual CERC-501, which doesn't seem to dissolve very easily.
The fact that CERC-501 also seems to have a very long half-life implies that it's a fairly stable compound as well, imho.
Edited by Stinkorninjor, 12 June 2017 - 02:25 PM.
Posted 12 June 2017 - 02:28 PM
Guys what is the dosing for a 90kg weight man ? I got my cerc501 today
/edit
Is it supposed to be yellow and sticky ? Can i disolve it ?
I believe the test-data have shown that as long as you keep below 25 mg, the compound is very selective for Kappa, so you can't go above that, at least. (otherwise it'll start antagonizing mu as well)
So... 10 mg? That seems to occupy the kappa-receptors significantly in the tests, so it seems like a reasonable dosage to start with.
I myself am probably going to be going with about 10 mg per dosing.
Posted 13 June 2017 - 07:20 AM
SO!
The journey towards figuring the compound out, continues! I've found quite a bit of data regarding Alvimopan, which is a drug closely related to JDtic, and JDtic appears to be closely related to CERC-501, so here we go, some similarities are bound to be shared.
https://www.drugbank.ca/drugs/DB06274
State
Solid Experimental Properties Property Value Source water solubility <0.1 mg/mL FDA Label Predicted Properties Property Value Source Water Solubility 0.00834 mg/mL ALOGPS logP 3.25 ALOGPS logP 0.82 ChemAxon logS -4.7 ALOGPS pKa (Strongest Acidic) 3.71 ChemAxon pKa (Strongest Basic) 10.66 ChemAxon Physiological Charge 0 ChemAxon
As you can see... the water solubility of Alvimopan, is fairly bad... Which does seem similar to our friend CERC-501.
Alvimopan has a "Physiological Charge of 0" as well, hmm... I believe this could be why Alvimopan is not very water-soluble.
Right, now, let's have a look at JDtic again, and see what Puchem says about its chemical properties, and how comparable they are to Alvimopan.
https://pubchem.ncbi...ical-Properties
Hmm...
No solubility-data whatsoever is presented. It does mention this though:
"Formal Charge of 0"
Is this merely another term for physiological charge? If so, this then implies that JDtic is not very water-soluble either... probably similar to Alvimopan. OK! What do you think, guys? Are we closer towards figuring this sh*t out? I think we are, at least a little bit...
Let's see... Here's a video on the subject-matter, I believe - Solubility.
https://www.khanacad...-compounds-redo
Posted 13 June 2017 - 11:58 PM
I think because it has other mechanisms of action at different receptor sites that can have an antidepressant affect. ex 5ht2,3 receptor antagonistHi guys, I believe that someone know the answer. I have a question:
How is it possible that mianserin which is kappa receptor AGONIST can be a working proven antidepressant if its mechanism of action is opposite to cerc501 ?
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