238 replies to this topic

[3AlarmLampscooter]

Looks like an interesting drug.

Safety, pharmacokinetics, and effects on cognitive function of multiple doses of GTS-21 in healthy, male volunteers. (PMID:12629535)

This study was designed to determine the safety, tolerability, pharmacokinetics and effects on cognitive function of GTS-21 in healthy, male volunteers. A total of 18 subjects were randomized to GTS-21 (25, 75 and 150 mg) or placebo administered three times daily (first 4 days, once on Day 5) for three, 5-day sessions. GTS-21 was well tolerated up to doses of 450 mg/day, with no clinically significant safety findings. C(max) and the area under the plasma concentration of GTS-21 and the metabolite 4-OH-GTS-21 increased in a dose-related fashion; although considerable intersubject variability occurred, it decreased with continued dosing. GTS-21 showed statistically significant enhancement of three measures of cognitive function (attention, working memory, episodic secondary memory) compared to placebo. A relationship between exposure to GTS-21 and the magnitude of the cognitive response was apparent, with maximal effect approached for doses between 75 and 150 mg three times a day. These data indicate that GTS-21 may represent a novel treatment for dementia.

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Edited by 3AlarmLampscooter, 08 July 2013 - 04:50 AM.

[Reformed-Redan]

Yup quite interesting. Nootropic effects should be prominent as with PRL-8-53. Compare these structures:
WAY-317,538

GTS-21:

PRL-8-53

Only problem is that these seem to be partial or full agonists leading to potential downregulation or tolerance.

[telight]

Yup quite interesting. Nootropic effects should be prominent as with PRL-8-53. Compare these structures:
WAY-317,538

GTS-21:

PRL-8-53

Only problem is that these seem to be partial or full agonists leading to potential downregulation or tolerance.

These structures are completely different.

[Reformed-Redan]

Excuse me. I meant WAY and PRL.

[3AlarmLampscooter]

I've been mulling over perhaps getting this one synthesized for a while.

I've been quoted $12,500 for a 100g synth. Works out to $3.13 to $18.75 a dose from the 25-150mg range used in clinical trials. Pricey, but I'm still possibly inclined to proceed. I'll do a bit more shopping around. That, and maybe start looking at some more simple nicotinic agonists as alternatives.

I may try sourcing some quotes for WAY-317,538, as it is supposedly "easy to synthesize", and thus probably cheap(er)

Edited by 3AlarmLampscooter, 05 September 2013 - 08:12 AM.

[p3x888]

Did you ever make any headway on this?

[scibor1]

Is gts-21/dmxba available?

[3AlarmLampscooter]

I'm still definitely down for a group buy if we can get a much better price than $125/g.

Anyone wanna submit quotes to their favorite labs?

[formergenius]

I believe there were a few alpha7nAChR agonist requests, so perhaps you'll draw more people when you explain that this is its primary MoA.

[3AlarmLampscooter]

I believe there were a few alpha7nAChR agonist requests, so perhaps you'll draw more people when you explain that this is its primary MoA.

Hah! Never even hit me that I didn't mention this in the OP! Derp.

GTS-21 = α7 Nicotinic Receptor Agonist

Also, a new paper has come out expanding on pathways of the anti-inflammatory properties of this class of drugs: http://www.ncbi.nlm....les/PMC3817544/

[Overman]

Please put me in for the group buy.

[Overman]

Forgive my zeal, I've missed out on every other buy. Not to mention the fact that this compound seems especially promising.

[scibor1]

a group boy? im in

[bkaz]

I am in, probably.

[mait]

Count me in as well!

[uralsky]

in, if reasonable price

[Reformed-Redan]

I'll see what my supplier has to say about this.

[Reformed-Redan]

Here is a picture of most a7n agonists or partial agonists. If anyone could get tthrough the paywall that would be nice and label some of the compounds there. Like 19, 23. 19 looks interesting.

Sry, here is the link:
http://journals.prou...064020&p_IsPs=N

Edited by yadayada, 29 December 2013 - 06:48 PM.

[Reformed-Redan]

My supplier indicated that pure anabaseine, which is the backbone of GTS-21, could more readily be provided. It's a potent agonist at the nicotinic receptors and would be maybe worth a trial?
More info:
http://link.springer...1007/BF02480382
and derivatives of anabaseine:
http://pubs.acs.org/....1021/ml400278r

[megatron]

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.

Edited by Megatrone, 29 December 2013 - 10:12 PM.

[scibor1]

My supplier indicated that pure anabaseine, which is the backbone of GTS-21, could more readily be provided. It's a potent agonist at the nicotinic receptors and would be maybe worth a trial?
More info:
http://link.springer...1007/BF02480382
and derivatives of anabaseine:
http://pubs.acs.org/....1021/ml400278r

Yes, yes, yes...
Beautiful information

[Flex]

Here is a picture of most a7n agonists or partial agonists. If anyone could get tthrough the paywall that would be nice and label some of the compounds there. Like 19, 23. 19 looks interesting.

Sry, here is the link:
http://journals.prou...064020&p_IsPs=N

Lol, Where's Wally

Edited by Flex, 30 December 2013 - 05:25 PM.

[megatron]

My supplier indicated that pure anabaseine, which is the backbone of GTS-21, could more readily be provided. It's a potent agonist at the nicotinic receptors and would be maybe worth a trial?
More info:
http://link.springer...1007/BF02480382
and derivatives of anabaseine:
http://pubs.acs.org/....1021/ml400278r

Did you get a quote for GTS-21?

What also greatly triggers my interest in this drug is that these effects were seen in humans, not just rats.

Edited by Megatrone, 30 December 2013 - 07:41 PM.

[3AlarmLampscooter]

I'm putting a request in on /r/scholar.

Here's the fulltext on another review that cites it, which I had access to: http://ge.tt/3UpgQvB1/v/0

There are plenty more and newer agonists/PAMs also.

Of the ones you mentioned, compound 19 is 3-{[2-(pyridin-3-yl)-3,4,5,6-tetrahydropyridin-3-ylidene]methyl}-1H-indol-1-yl and has no pubchem entry, 23 is 2,3-Dihydroindol-5-ol and looks to be a pretty potent dopamine agonist also.

Edited by 3AlarmLampscooter, 31 December 2013 - 07:14 PM.

[Reformed-Redan]

PAM's at the GluR₅ seem like interesting targets for nootropic potential?

http://jpet.aspetjou...jpet.113.206623

[formergenius]

What about EVP-6124? Perhaps it's cheaper? It's an a7nAChR agonist as well.
There's no wiki on it, but it has been tested in humans, see here. I believe YoungS is going to participate in a trial as well.
edit: If I'm not mistaken, it's also much more potent (2mg), hence even if a gram is around the aforementioned price, it would be more bang for you buck.

Edited by formergenius, 06 January 2014 - 02:22 AM.

[megatron]

I have been quoted $3300 for 100g GTS-21, which is still expensive, but not too bad. Lead time is two months. However it will probably be a lot cheaper if we go with 200-300g. I don't think the price will be too bad, if we get 200g and 15-20 persons. What say you? Should we acquire this drug or do you guys want to find something cheaper? I'm definitely down for at least 10g.

Edited by Megatrone, 06 January 2014 - 01:59 PM.

[megatron]

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

[formergenius]

I doubt anyone is willing to put down $300+ for this..
What about TC-5619?

Edited by formergenius, 07 January 2014 - 02:09 PM.

[bkaz]

From the papers posted here, a7nAChR seem to be targeted for its anti-inflammatory effects. But do these agonists, etc., have any advantage over nicotine in improving attention / focus?