LONGECITY

Small correction of the first post @megatron:
EVPs half-life is not 4 hrs. it is the Tmax 4 hrs, that is the time of max blood concentration after ingestion.
Also, the solubility in water is low, estimated from chemspider as ~10 - 100 mcg/mL. Meaning that to dissolve in water 1mg one would need 10 - 100 mL. medchemexpress.com sells EVP and lists it as soluble in DMSO.
Should be soluble in alcohol though

Hi,

Medchemexpress lists two options for EVP-6124: just EVP-6124 and EVP-6124 hydrochloride. Are there any remarkable differences between those two in respect to pharmacodynamics and pharmacokinetics? Which one of those two is is more stable as powder and / or in alcohol solution?

After you ingest should be not much difference. Expect hydrochloride form to be more soluble.
By the way EnVivo used 2 mg/Liter solution in water to dose rats

Im in for 30mg

I agree for 30 mg
Edited by scibor1, 01 February 2014 - 09:41 AM.

OK, so far we have 11 participants. Keep'em coming

How would you compare it to PRL5-83 is regard of memory in general ?

In July 2012, EnVivo announced positive results of its six-month, double-blind Phase 2b clinical trial that evaluated encenicline (EVP-6124) against placebo in patients with mild to moderate Alzheimer's disease. Results demonstrated that dosing with encenicline resulted in statistically significant improvements in cognition and clinical function, meeting both of the trial's primary endpoints. The data also showed statistically significant results across secondary endpoints of other cognitive and clinical measures. In October 2012, EnVivoannounced additional pharmacokinetic and pharmacodynamic analyses from the Phase 2b trial, which demonstrated a significant relationship (p=0.003) between encenicline plasma concentrations and the probability of experiencing an improvement in cognition.

Edited by Megatrone, 01 February 2014 - 04:24 PM.

Megaton do you want me to help ship from the us or not?

Megaton do you want me to help ship from the us or not?

Possibly, as for now I'm looking for a member with high reputation and who has been part of this community for a longer time.

it may work of a alzeimer patient, but why would it works on anyone ? And what are the other psychotropic effect? I don't want to have a good memory with a great fog lol.

payment by paypal?

payment by paypal?

Yes I will use Payitsquare to collect payments, so you will have to set this up with your PayPal account. It is not very hard or much work.

Hey from NZ,finally got around to registering on this forum, I've been lurking around for a few years and been keeping a close eye on some intriguing new nootropics.

Anyway, Megatrone, count me in for 60mg. I'm interested in exploring the potential of this compound to offset the decline in cognition from post nicotine addiction.

Cheers
Edited by Dazzcat, 03 February 2014 - 10:34 PM.

Hey from NZ,finally got around to registering on this forum, I've been lurking around for a few years and been keeping a close eye on some intriguing new nootropics.

Anyway, Megatrone, count me in for 60mg. I'm interested in exploring the potential of this compound to offset post nicotine addiction cognitive side effects.

Cheers

Awesome!

We only need 60mg to meet the minimum order quantity.

From what I understand this compound may only be suited for intermittent long term use due to potential for alpha-7 nicotinic receptor desensitisation?

In my experience with chronic daily nicotine intake (via 1mg sublingual), a significant tolerance occurs to the cognitive benefits, however nicotine with it's broad activity across many nicotinic receptors which trigger downstream dopamine release, side effects from long term use is of course expected and my experience may have little bearing on chronic EVP-6124 use.
Edited by Dazzcat, 03 February 2014 - 11:20 PM.

I'm in for 90mg personally, and willing to act as a US reshipper. It's awesome we'll finally get an alpha-7 nicotinic agonist on the market. From what I've studied on receptor kinetics, ultimately combining with an alpha-7 nicontinic positive allosteric modulator will reduce receptor desensitization, and provides a viable long term strategy.

The magnitude of desensitization remains to be seen though. EVP-6124 is a partial agonist, where as nicotine is IIRC a full agonist. Full agonists generally cause much greater receptor desensitization than partial agonists.


When it comes to payment however, I'm however no longer willing to deal with WayFoul. I'll sooner pay with DogeCoins than deal with PayPal again.

such transaction fees, very international espionage, much needless security theater, wow

I'm in for 90mg personally, and willing to act as a US reshipper. It's awesome we'll finally get an alpha-7 nicotinic agonist on the market. From what I've studied on receptor kinetics, ultimately combining with an alpha-7 nicontinic positive allosteric modulator will reduce receptor desensitization, and provides a viable long term strategy.

The magnitude of desensitization remains to be seen though. EVP-6124 is a partial agonist, where as nicotine is IIRC a full agonist. Full agonists generally cause much greater receptor desensitization than partial agonists.


When it comes to payment however, I'm however no longer willing to deal with WayFoul. I'll sooner pay with DogeCoins than deal with PayPal again.

such transaction fees, very international espionage, much needless security theater, wow

That's very good new! We now have passed the minimum order quantity and have a US reshipper in place. I'm still on the lookout for an EU reshipper, but one member is currently on hold and may be willing to do this. Once we have the European reshipper in place, I will PM you guys the link for the Payitsquare site. The payment deadline will be approx. one week. Other members are free to join the group buy as long as we don't have 20 participants and the payment deadline has not ended. Finally things are looking brighter for this group buy

I'm in for 90mg personally, and willing to act as a US reshipper. It's awesome we'll finally get an alpha-7 nicotinic agonist on the market. From what I've studied on receptor kinetics, ultimately combining with an alpha-7 nicontinic positive allosteric modulator will reduce receptor desensitization, and provides a viable long term strategy.

The magnitude of desensitization remains to be seen though. EVP-6124 is a partial agonist, where as nicotine is IIRC a full agonist. Full agonists generally cause much greater receptor desensitization than partial agonists.


When it comes to payment however, I'm however no longer willing to deal with WayFoul. I'll sooner pay with DogeCoins than deal with PayPal again.

such transaction fees, very international espionage, much needless security theater, wow

That's very good new! We now have passed the minimum order quantity and have a US reshipper in place. I'm still on the lookout for an EU reshipper, but one member is currently on hold and may be willing to do this. Once we have the European reshipper in place, I will PM you guys the link for the Payitsquare site. The payment deadline will be approx. one week. Other members are free to join the group buy as long as we don't have 20 participants and the payment deadline has not ended. Finally things are looking brighter for this group buy

Thank You for organizing this group buy. At least for me EVP-6124's potential in WM enhancement seems to be the most promising avenue to achieve increase in mental abilities that would have biggest effect in real life job and academic outcomes.

In for 30mg.

From what I've studied on receptor kinetics, ultimately combining with an alpha-7 nicontinic positive allosteric modulator will reduce receptor desensitization, and provides a viable long term strategy.

The magnitude of desensitization remains to be seen though. EVP-6124 is a partial agonist, where as nicotine is IIRC a full agonist. Full agonists generally cause much greater receptor desensitization than partial agonists.

Hey 3AlarmLampscooter, glad to have you on board. After doing more research on EVP-, I also agree that receptor desensitization may not be an issue, perhaps only at higher doses which appear to have negative implications on memory in rat studies anyway. So when you talk about PAM's for Alpha-7 agonist potentiation, you mean something like Nefiracetam? From my limited knowledge I assume the other racetam's mostly have AMPA allosteric modulation, though this property could also synergize with EVP-.

Here is some quotes taken from the hallmark study that are of relevant interest to alpha-7 nicotinic receptor desensitization and how it is suggest there is another mechanism of action besides a7 nAChR affinity.

Based on the pharmacokinetic data, estimation of the maximum effective brain concentration in the ORT (object recognition test) after a dose of 0.3 mg/kg, p.o. was about 2 nM (total concentration of EVP-6124) and less than 1 nM free drug. Thus, in spite of the high affinity of EVP-6124 for a7 nAChRs, a concentration lower than 3 nM was clearly insufficient to activate the receptor in in vitro studies, suggesting an alternative mechanism of action...

...sustained exposure to a concentration of EVP-6124 below 1 nM potentiated the ACh-evoked current. Increasing the EVP-6124 concentration to 3 nM or above, caused a marked reduction of the ACh-evoked current that was attributable to receptor desensitization......The pro-cognitive effects after EVP-6124 administration appear to have occurred at brain concentrations below those that caused desensitization.

...the presence of a low concentration of EVP-6124, in the sub-nanomolar range increased the ACh-evoked current by a factor of two or more


...Although different mechanisms can be postulated to account for the observed potentiation, the simplest and most probable model considers the co-agonistic behavior of EVP-6124 and ACh at a7
nAChRs.

So it then goes on to explain what they mean by co-agonism and why it leads to an improved side effect profile over full agonism. I found it rather interesting that nAChR's have two binding sites for ligands and there must be two ligands bounded to the receptor to trigger channel opening and an inward current.

It appears to be more favourable to increase the efficiency of EVP- with the addition of an acetylcholinesterase inhibitor (rather than increasing dosage of EVP-) due to the increased potentiation from ACh occupying a binding site. This approach avoids receptor desensitization associated with higher doses of EVP-.

Source:- http://aimday.se/wp-...oad/EVP6124.pdf
Edited by Dazzcat, 04 February 2014 - 10:54 PM.

I'm on my phone. What is thr cost per 30 mg to join?

"30mg, the total cost will be: $102 (drug) + $17 (shipping) = $119"

- quoted by Megatrone
Edited by Dazzcat, 05 February 2014 - 04:42 AM.

Megatrone 60mg
mait 30mg
prx888 30mg
aarfai 60mg
formergenius 30mg
bkaz 30mg
Ampamet 30mg
Muad-Dib 30mg
Ashenhurst 30mg
RAFT LIFE 30mg
scibor1 30mg
Dazzcat 60mg
3AlarmLamscooter 90mg
focus83 30mg

So far we have 14 participants and a total of 570mg.
Edited by Megatrone, 05 February 2014 - 11:47 AM.

Update

I have found a reputable member willing to do the shipping for European participants; Raza. This means that I will set up Payitsquare hopefully today and start collecting payments tomorrow.


I'm still wondering what solvent we will be using. We will have to rinse the plastic bags to not let any of the drug go to waste, but if we choose DMSO, isn't there a danger that the DMSO might dissolve some of the plastic bag?

Megatrone will the US shipper you have chosen be handling all of North America? As in Canada as well?

Count me in for 30mg.

That's great news!
Unfortunately, if you will be using DMSO as a solvent, I'm afraid that I won't participate. There's controversy about the safety of DMSO, and indicators that it may be neurotoxic, which is too ironic for my taste.

Update

I have found a reputable member willing to do the shipping for European participants; Raza. This means that I will set up Payitsquare hopefully today and start collecting payments tomorrow.


I'm still wondering what solvent we will be using. We will have to rinse the plastic bags to not let any of the drug go to waste, but if we choose DMSO, isn't there a danger that the DMSO might dissolve some of the plastic bag?

Please please no DMSO. Why not try to use alcohol as solvent as user uralsky recommended if using solvent is really required. Or maybe just ship powder to all users and everyone can decide, which solvent to use. Additionally I think that shipping powder is easier than liquid increasing our chances to avoid packages being seized by customs.

Mmmm dmso garlic breath. I thought we learned our lesson with bpap buy

That's great news!
Unfortunately, if you will be using DMSO as a solvent, I'm afraid that I won't participate. There's controversy about the safety of DMSO, and indicators that it may be neurotoxic, which is too ironic for my taste.

Update

I have found a reputable member willing to do the shipping for European participants; Raza. This means that I will set up Payitsquare hopefully today and start collecting payments tomorrow.


I'm still wondering what solvent we will be using. We will have to rinse the plastic bags to not let any of the drug go to waste, but if we choose DMSO, isn't there a danger that the DMSO might dissolve some of the plastic bag?

Please please no DMSO. Why not try to use alcohol as solvent as user uralsky recommended if using solvent is really required. Or maybe just ship powder to all users and everyone can decide, which solvent to use. Additionally I think that shipping powder is easier than liquid increasing our chances to avoid packages being seized by customs.

Mmmm dmso garlic breath. I thought we learned our lesson with bpap buy

I see now that my post may have been a bit misleading. I meant as a solvent after everyone has received their share. To dissolve it yourself. I did not mean to receive it from the supplier presolved. Everyone will receive their share in powder form, so it it up to yourself as to decide how you want to dissolve it. My intention was only to get some discussion going around this

Megatrone will the US shipper you have chosen be handling all of North America? As in Canada as well?

That was the plan.
Edited by Megatrone, 06 February 2014 - 07:15 PM.

Actually when it comes to customs, a liquid in something that does not appear to be a pharmaceutical is going to be the most likely to get through. Powders get stopped a lot more. FYI, if you can mail it in a small envelope instead of a package, it is much less likely to come under any scrutiny. Overnight packages containing white powders tend to be the most likely to get stopped.

Of course this isn't an illegal drug, and on chemical analysis would not even be mistaken for one, but you'll never get to that point in the first place with good stealth.