LONGECITY

Well yes; nicotine targets other cholinergic receptors as well, whereas these do not. And then there's the entire debate on whether or not nicotine is bad for you.
Found this news article today, which claims a7nAChRs are heavily situated in the prefrontal areas.

Very interesting, thanks Former! Here's a full paper: http://www.ncbi.nlm....les/PMC3718126/
Still reading the paper, but looks exciting.

Ahh I couldn't find any scientific basis for it; nice!
This study states that a7nAChR agonists enhance GABAergic transmission in the hippocampus.
That, among other things, is mentioned in this pipeline report, which also mentions another candidate: MEM-3454, however it's also a 5HT3 antagonist.

In the future I hope to take a degree in neuroscience, but as of now my knowledge within neuroscience is very limited. Therefore I want to know how different studies can claim that very different drugs working on completely diverse receptors in the brain can give the same effects, i.e. improved working memory, LTP, memory retention etc? I'm talking about studies on humans, not rodents where it's hard to determine effects on different kinds of memory.

Think of the brain and all its faculties as a large structure held up by many, many pillars. These pillars are the neurotransmitters/receptors. In every facet of consciousness, every neurotransmitter comes into play either directly or indirectly. Altogether these receptors help to regulate every and all executive and non-executive function, and when any individual neurotransmitter is thrown of balance it also throws others off-balance/changes your neurochemistry. Memory is an incredibly complicated thing. Generally speaking, our entire basis for consciousness is 100% dependent on memory. Without memory, you don't create "you". Your experiences create who you are. Without the ability to remember your experiences, you wouldn't have you. That said, the brain has many many means by which to create and regulate memories, and uses many neurotransmitters/receptors to do so--seeing as it is, after all, so incredibly complicated and intertwined.

I feel like this was a mildly jumbled way to explain it, but I hope that helps it make more sense. Everything in the brain is dependent on everything else, which is why almost every single disease in theory has a multifaceted approach to its resolution. Nothing in our brain/body is ever dependent on exclusively one neurotransmitter or mechanism. Absolutely nothing.

OK it seems that in PFC α7-nAChR is preferentially responsible for working memory, & β2* nAChR for perceptual attention? This is seems to be a good review article: https://www.ncbi.nlm...pubmed/23856288 :
"Nicotinic acetylcholine receptors controlling attention: behavior, circuits and sensitivity to disruption by nicotine,

anyone has full access?
On the other hand, this paper: http://www.ncbi.nlm....pubmed/24089524 claims that α7-nAChR up-regulation correlates with lung cancer?

Ahh I couldn't find any scientific basis for it; nice!
This study states that a7nAChR agonists enhance GABAergic transmission in the hippocampus.
That, among other things, is mentioned in this pipeline report, which also mentions another candidate: MEM-3454, however it's also a 5HT3 antagonist.

Can you provide a structure for MEM-3454?

Also can someone bash this paywall?

http://journals.prou...d=3853&p_IsPs=Y

I think GTS-21 sounds like a real good shot at trying out a7n agonists. I'll try and get an update from the labs.

Hmm that would make PAMs less preferable than agonists, no?
And agonists may be good for smokers?

Unfortunately I believe MEM-3454 is in the same boat as NRX-1074; structure undisclosed (found in this list of a7nAChR agonists in development). Though it could use an update, cause it doesn't note that AZD-0328 has been discontinued. Though I remember reading elsewhere that the structure hasn't yet made public.. I'll try to search through patents though.

Looking forward to that update! Any reason in particular why not to use TC-5619 instead? Structure is available, human trials have been successful, confirmed safety, etc.

This paper: http://www.jneurosci.../30/9/3518.long quantifies the effect on working memory, in mice:
"Substantiating the role of α7 nAChR in controlling the duration of release events, stimulation of α7 nAChR produced cholinergic transients that lasted 10- to 15-fold longer than those evoked by nicotine."

So, definitely worth trying, I am in for any reasonable group-buy!

I tried finding links to possible anxiolysis outside of reduction of psychotic symptoms in schizophrenic individuals, but all I could come up with was this paper, though it's unavailable online:
(1998) AR-R 17779, a selective α7 nicotinic agonist, has anxiolytic and sensory gating-enhancing properties and reduced nicotine-like side effects. Soc Neurosci Abstr 24:331.11.

In any case; it does seem to indicate that these ligands may have anxiolytic qualities as well. And personally I could most definitely use some sensory gating enhancement.
Quite excited for this all

α7 is known to be anti-inflammatory, which may have anxiolytic effects downstream.

Also, the paper I just quoted mentions that these working-memory effects are dopamine-mediated. Tonic DA is also anxiolytic, I think.
Edited by bkaz, 09 January 2014 - 10:18 PM.

Maybe TC-5619 is not such a suitable candidate after all.

Guess it's gonna have to be GTS, EVP, or MEM then..

Sorry guys, you're on your own with a group buy for this. I'm no longer taking part in group buys. Thanks.

Sorry guys, you're on your own with a group buy for this. I'm no longer taking part in group buys. Thanks.

Ahh pity. I'm assuming the same goes for the 7,8-DHF buy?

Who is head of group "buy" now?
Edited by scibor1, 15 January 2014 - 07:45 PM.

It has been decapitated.

Yadayada share sellers' contact us

^Please*

In.

In and in.

In.

Would you be willing to divulge your supplier should someone offer to host this buy?
edit: I know a source for EVP-6124, but it's ~$130/10mg, possible cheaper when buying more. Dosage is 0.3-2mg/day.
Edited by formergenius, 17 January 2014 - 06:43 PM.

So, yadayada, were you able to find a cheaper reputable supplier?

In.

Would you be willing to divulge your supplier should someone offer to host this buy?
edit: I know a source for EVP-6124, but it's ~$130/10mg, possible cheaper when buying more. Dosage is 0.3-2mg/day.

Would you try and get quotes for larger amounts? I would prefer GTS-21 though, since it has been through the most testing, but if people think it's too steep it would probably be OK trialing a cheaper altnernative.
Edit: Failed applying basic arithmetics :( That is kind of steep, and I'd rather just go with GTS-21 then, if we can't get the price down.
Edited by Megatrone, 24 January 2014 - 06:46 PM.

In.

Would you be willing to divulge your supplier should someone offer to host this buy?
edit: I know a source for EVP-6124, but it's ~$130/10mg, possible cheaper when buying more. Dosage is 0.3-2mg/day.

That price isn't awfully bad. At 0.25mg a day it'll last us 40 days. Would you try and get quotes for larger amounts? I would prefer GTS-21 though, since it has been through the most testing, but if people think it's too steep it would probably be OK trialing a cheaper altnernative.

I don't think it's too steep at all, and I agree with everything you've said. The number of performed human trials is very reassuring wrt to short term safety.

In.

Would you be willing to divulge your supplier should someone offer to host this buy?
edit: I know a source for EVP-6124, but it's ~$130/10mg, possible cheaper when buying more. Dosage is 0.3-2mg/day.

I have been quoted $34/10mg (not very expensive) for 500mg from a trusted lab, so do you guys want to test agonists for the α_7-nicotinic receptor?

For EVP or GTS? I'm assuming EVP. Yes; count me in for sure.

For EVP or GTS? I'm assuming EVP. Yes; count me in for sure.

Sorry, it was for EVP-6124 yes I really want to try GTS-21, but I'm willing to go with EVP-6124 for now. Don't you think it should at least give us a hint if agonists for the a7 receptor has any future? 500mg was minimum order quantity, so we should at least get a month's supply each. 30mg+ each and no more than 20 participants to not make this more difficult than it needs to be. Personally, I'll probably get 50mg.

Alright; I suggest you start a new topic with "Group Buy" in the title if you want to take the lead on this one. It'd be nice to have that clearly visible.
I haven't been that scrutinizing, but they seem pretty similar to me. Plus, you might catch more participants with EVP; there are a number of people with schizophrenia on this forum who might be interested in EVP but not in GTS.
My memory sucks, but I think GTS lacked the sensory gating enhancing effects, whereas EVP didn't.

Anyhow; $100 buy-in is reasonable and acceptable. How trusted is the lab? (as in: where is it located?)

$3300/100g , $5500/200G, $7200/300G.

Is this price still accurate?

At 100G, that works out to $33 per gram. If we took the max dosage of 2mg, one gram would work out to 500 doses. To me, this is very good. so we need 33 people to buy 3 grams each. Is this doable?

For EVP or GTS? I'm assuming EVP. Yes; count me in for sure.

Sorry, it was for EVP-6124 yes I really want to try GTS-21, but I'm willing to go with EVP-6124 for now. Don't you think it should at least give us a hint if agonists for the a7 receptor has any future? 500mg was minimum order quantity, so we should at least get a month's supply each. 30mg+ each and no more than 20 participants to not make this more difficult than it needs to be. Personally, I'll probably get 50mg.

Count me in too. What's the half-life?

For EVP or GTS? I'm assuming EVP. Yes; count me in for sure.

Sorry, it was for EVP-6124 yes I really want to try GTS-21, but I'm willing to go with EVP-6124 for now. Don't you think it should at least give us a hint if agonists for the a7 receptor has any future? 500mg was minimum order quantity, so we should at least get a month's supply each. 30mg+ each and no more than 20 participants to not make this more difficult than it needs to be. Personally, I'll probably get 50mg.

Count me in too. What's the half-life?

Around 4h. From what I gather.