238 replies to this topic

[gamesguru]

i think the alpha 7 receptor is activating other pathways, dopamine and serotonin. that helps explain why nicotine withdrawal makes anxiety disorder (methinks even non-ADD anxiety) 10x worse.

Transdermal Nicotine in Adult ADHD With Depression and Anxiety
James A. Cocores, M.D. (2008)

Sir: Focusing and memory ability are dysfunctional in attention-deficit/hyperactivity disorder (ADHD),1 which commonly co-occurs with depression and anxiety.2 Treatment with methyl-phenidate or amphetamine frequently corrects inattentiveness and memory impairment, but is less reliable in the alleviation of the accompanying depression and anxiety. These medicines have depression and anxiety as reported side effects. In addition to the involvement of dopaminergic and noradrenergic neurons, there is evidence to suggest that cholinergic neurons are involved in the biobehavior associated with ADHD.3
Nicotine-dependent individuals experience more inattentiveness, forgetfulness, depression, and anxiety during withdrawal, and nicotine replacement is thought to reverse withdrawal-induced focusing and memory impairment,4 depression,5 and anxiety.6 Changes in focus and memory ability, associated with nicotine dependence and replacement treatment, are directly mediated by nicotinic-cholinergic neurons, and depression and anxiety are thought to be indirectly mediated by pathways between nicotinic-cholinergic receptors and dopaminergic, nor-adrenergic, serotonergic, and gabaminergic neurons.7
The following report illustrates a case of adult ADHD associated with depression and anxiety that responded to transdermal nicotine patches.

Alpha 7 nicotinic receptor subunit is present on serotonin neurons projecting to hippocampus and septum.
Aznar S1, Kostova V, Christiansen SH, Knudsen GM. (2005)

The serotonergic transmitter system regulates hippocampal activity through its raphe projection to hippocampus and medial septum/diagonal band of Broca complex (MS/DBB), and most likely also indirectly through its interaction with the cholinergic neurotransmitter system. Nicotine, e.g., enhances hippocampal serotonin release probably through presynaptic nicotinic receptors. We investigated the possible presence of the alpha 7-nicotinic subunit on serotonergic neurons projecting to hippocampus and MS/DBB. By retrograde neuronal tracing, hippocampal serotonergic neurons were identified and with double fluorescence immunostaining and Alexa-488 bound alpha-bungarotoxin the presence of active alpha 7 receptor on their soma was determined. Most of the retrogradely labeled serotonin neurons contained the alpha 7 subunit. A low degree of colocalization between alpha-bungarotoxin and serotonin-positive neurons suggest that the alpha 7 subunit may be transported anterogradely to the serotonergic axonal terminals.

Involvement of alpha 7 nicotinic acetylcholine receptors in gene expression of dopamine biosynthetic enzymes in rat brain.
Serova L1, Sabban EL. (2002)

Brain dopaminergic systems are critical in mediating the physiological responses to nicotine. The effects of several concentrations of nicotine (0.08, 0.17, or 0.33 mg/kg body weight) and involvement of alpha7 nicotinic acetylcholine receptors (nAChRs) in gene expression of key enzymes in dopamine biosynthesis were evaluated in the ventral tegmental area (VTA) and substantia nigra (SN), cell bodies of the mesocorticolimbic and nigrostriatal pathways. Nicotine elicited a dose-dependent elevation of mRNA for tyrosine hydroxylase (TH), the rate-limiting enzyme in dopamine biosynthesis in VTA and SN. The VTA was more sensitive to lower concentrations of nicotine with maximal response observed with the lowest dose of nicotine. Nicotine also elevated mRNA levels of GTP cyclohydrolase I (GTPCH), rate limiting in biosynthesis of TH's essential cofactor tetrahydrobiopterin in both dopaminergic locations. The changes in TH and GTPCH mRNAs were correlated. Pretreatment with the alpha7 nAChR antagonist methyllycaconitine prevented the nicotine-induced rise in TH or GTPCH mRNA in VTA and SN. Administration of alpha7 nAChR agonist 3-[2,4-dimethoxybenzilidene]anabaseine at 1 to 10 mg/kg or (E,E-3-(cinnamylidene)anabaseine at 0.3 to 1 mg/kg increased TH mRNA in VTA and SN, but not in peripheral catecholaminergic cells. Thus, agonists of alpha7 nAChRs have therapeutic potential for increasing TH gene expression in dopaminergic regions without some of nicotine's disadvantages, such as its harmful effects on the cardiovascular system. The findings indicate that nicotine may regulate dopamine biosynthesis by alterations in gene expression of TH and its cofactor. The alpha7 nAChRs are involved in mediating these effects of nicotine.

alpha7 and non-alpha7 nicotinic acetylcholine receptors modulate dopamine release in vitro and in vivo in the rat prefrontal cortex.
Livingstone PD1, Srinivasan J, Kew JN (2009)

Nicotine enhances attentional and working memory aspects of executive function in the prefrontal cortex (PFC) where dopamine plays a major role. Here, we have determined the nicotinic acetylcholine receptor (nAChR) subtypes that can modulate dopamine release in rat PFC using subtype-selective drugs. Nicotine and 5-Iodo-A-85380 (beta2* selective) elicited [(3)H]dopamine release from both PFC and striatal prisms in vitro and dopamine overflow from medial PFC in vivo. Blockade by dihydro-beta-erythroidine supports the participation of beta2* nAChRs. However, insensitivity of nicotine-evoked [(3)H]dopamine release to alpha-conotoxin-MII in PFC prisms suggests no involvement of alpha6beta2* nAChRs, in contrast to the striatum, and this distinction is supported by immunoprecipitation of nAChR subunits from these tissues. The alpha7 nAChR-selective agonists choline and Compound A also promoted dopamine release from PFC in vitro and in vivo, and their effects were enhanced by the alpha7 nAChR-selective allosteric potentiator PNU-120596 and blocked by specific antagonists. DNQX and MK801 inhibited [(3)H]dopamine release evoked by choline and PNU-120596, suggesting crosstalk between alpha7 nAChRs, glutamate and dopamine in the PFC. In vivo, systemic (but not local) administration of PNU-120596, in the absence of agonist, facilitated dopamine overflow in the medial PFC, consistent with the activation of extracortical alpha7 nAChRs by endogenous acetylcholine or choline. These data establish that both beta2* and alpha7 nAChRs can modulate dopamine release in the PFC in vitro and in vivo. Through their distinct actions on dopamine release, these nAChR subtypes could contribute to executive function, making them specific therapeutic targets for conditions such as schizophrenia and attention deficit hyperactivity disorder.

[Junk Master]

My take is it was extremely helpful in stressful situations.  Also, it is a very nice complement to Modafinil.  Really clears up some of the racing thoughts, or hyper-focus issues that can accompany regular Modafinil use (which I would never recommend by I have sleep apnea AND idiopathic narcolepsy).

 

It's effects also seem to be cumulative.  So, I'd like to trial it long term but the cost is such, given the other supps/noots

/RC chems I'd still like to trial, I'd have to hold off for a little bit and then lower the dosage.

 

I didn't notice any additional effect between 150 mg and 300 mg.

 

When I take it again, I will definitely be capping it as it really aggravated my acid reflux!  It also stained most of my bathroom hand towels and I was pretty darn careful handling it.

 

All in all, I would not run it alone but only as part of a stack.  Or run it at a lower dose for a longer period of time and see how synergistic it became with occasional Modafinil/Tianeptine use.  

 

I have no idea how it would play with NSI-189, but would sure be interested to hear anyone's research as it might clean up some of the anxiety I felt with NSI-189 while ramping the dose up.  NSI-189, Tianeptine, and 21 might be a very interesting stack.

[gamesguru]

it seems to go well with everything! even other antidepressants.

 

Rhamnetin is an alpha-7 agonist found in cloves. this opens up new ideas, where there has been a longstanding tendency to attribute cloves' cognitive enhancing effect on AChE inhibitors.

A nicotinic receptor-mediated anti-inflammatory effect of the flavonoid rhamnetin in BV2 microglia.
Lutz JA1, Kulshrestha M2, Rogers DT3, Littleton JM4. (2014)

The alpha7 nicotinic acetylcholine receptor (nAChR) is a potential target in neuroinflammation. Screening a plant extract library identified Solidago nemoralis as containing methyl-quercetin derivatives that are relatively selective ligands for the alpha7 nAChR. Flavonoids are not known for this activity, so we screened a small library of pure flavonoids to confirm our findings. Some flavonoids, e.g. rhamnetin, displaced a selective alpha7 nAChR radioligand from rat brain membranes whereas similar structures e.g. sakuranetin, did not. To evaluate the contribution of this putative nAChR activity to the known anti-inflammatory properties of these flavonoids, we compared their effects on lipopolysaccharide induced release of inflammatory mediators from BV2 microglia. Both rhamnetin and sakuranetin reduced mediator release, but differed in potency (rhamnetin>sakuranetin) and the Hill slope of their concentration-response curves. For rhamnetin the Hill coefficient was >3.0 whereas for sakuranetin the coefficient was 1.0, suggesting that effects of rhamnetin are mediated through more than one mechanism, whereas sakuranetin has a single mechanism. nAChR antagonists decreased the Hill coefficient for rhamnetin toward unity, which suggests that a nAChR-mediated mechanism contributes cooperatively to its overall anti-inflammatory effect. In contrast nAChR antagonists had no effect on the potency or Hill coefficient for sakuranetin, but a concentration of nicotine (1μM) that had no effect alone, significantly increased the Hill coefficient of this flavonoid. In conclusion, the anti-inflammatory effects of rhamnetin benefit cooperatively from a nAChR-mediated mechanism. This action, together with potent free radical scavenging activity, suggests that flavonoids with alpha7 nAChR activity have therapeutic potential in neuroinflammatory conditions.

[Water Buffalo]

My take is it was extremely helpful in stressful situations.  Also, it is a very nice complement to Modafinil.  Really clears up some of the racing thoughts, or hyper-focus issues that can accompany regular Modafinil use (which I would never recommend by I have sleep apnea AND idiopathic narcolepsy).

 

It's effects also seem to be cumulative.  So, I'd like to trial it long term but the cost is such, given the other supps/noots

/RC chems I'd still like to trial, I'd have to hold off for a little bit and then lower the dosage.

 

I didn't notice any additional effect between 150 mg and 300 mg.

 

When I take it again, I will definitely be capping it as it really aggravated my acid reflux!  It also stained most of my bathroom hand towels and I was pretty darn careful handling it.

 

All in all, I would not run it alone but only as part of a stack.  Or run it at a lower dose for a longer period of time and see how synergistic it became with occasional Modafinil/Tianeptine use.  

 

I have no idea how it would play with NSI-189, but would sure be interested to hear anyone's research as it might clean up some of the anxiety I felt with NSI-189 while ramping the dose up.  NSI-189, Tianeptine, and 21 might be a very interesting stack.

 

I took NSI-189 with GTS-21 for about 4 months, and I think they are complimentary. NSI-189 was recently linked to changes in LTP and LTD in the hippocampus independent of NMDA receptors. I can't speak for anxiety induced by NSI-189, however the change in cognition that GTS-21 provides was anxiolytic for me. I would not be surprised if it affected dopamine and serotonin.
 

[Heisenburger]

i think the alpha 7 receptor is activating other pathways, dopamine and serotonin. that helps explain why nicotine withdrawal makes anxiety disorder (methinks even non-ADD anxiety) 10x worse.

 

Functional characterization of the novel neuronal nicotinic acetylcholine receptor ligand GTS-21 in vitro and in vivo.

 

2.4)-Dimethoxybenzylidene anabaseine dihydrochloride (GTS-21), a compound that interacts with rat neuronal nicotinic acetylcholine receptors (nAChRs), was evaluated using human recombinant nAChRs in vitro and various pharmacokinetic and behavioral models in rodents, dogs and monkeys. GTS-21 bound to human alpha 4 beta 2 nAChR (K1-20 nM) 100-fold more potently than to human alpha 7 nAChR, and was 18- and 2-fold less potent than (-)-nicotine at human alpha 4 beta 2 and alpha 7 nAChR, respectively. Functionally. GTS-21 stimulated [5H]dopamine release from rat striatal slices with an EC50 of 10 +/- 2 microM (250-fold less potent and 70% as efficacious as (-)-nicotine), an effect blocked by the nAChR antagonist dihydro-beta-erythroidine. However, GTS-21 did not stimulate human alpha 4 beta 2 nor human ganglionic nAChRs significantly. In vivo, GTS-21 had no adverse effect on dog blood pressure (< or = 2.5 micromol/kg i.v. bolus infusion), in marked contrast with (-)-nicotine, GTS-21 (-62 micromol/kg.s.e.) also did not cross-discriminate significantly with (-)-nicotine in rats and did not reduce temperature or locomotion in mice. Neither was it active in the elevated plus maze anxiety model (0.19-6.2 micromol/kg.IP) in normal mice. However, GTS-21 did improve learning performance of monkeys in the delayed matching-to-sample task (32-130 nmol/kg.i.m.).

 

Bolding mine.

[gamesguru]

250x less potent than nicotine? then again, nicotine is one of those things active in the microgram range...

[Ark]

What's GTS effects on the liver and kidneys?

[bossmanglb]

There is much evidence to suggest that some procognitive effects of GTS-21 and a7 nicotinic agonists generally are significantly delayed and/or only apparent after sustain administration:

 

Differential Immediate and Sustained Memory Enhancing Effects of Alpha7 Nicotinic Receptor Agonists and Allosteric Modulators in Rats

"Using the social discrimination test as a measure of short-term memory, we show that the α7 nAChR agonist A-582941 improves short-term memory immediately after repeated (7× daily), but not a single administration. 

 

Importantly, A-582941 and AVL-3288 increase short-term memory 24 hrs after repeated, but not a single, administration

 

 The α7 nAChR PAMs PNU-120596 and AVL-3288 do not affect short-term memory immediately after a single or repeated administration. This demonstrates a fundamental difference in the behavioral effects of agonists and PAMs that may be relevant for clinical development.

 

 In conclusion, both α7 nAChR agonists and PAMs exhibit sustained pro-cognitive effects after repeated administration, and altered levels of the α7 nAChR per se, or that of endogenous regulators of nAChR function, are likely not the major cause of this effect."

 

I found another mouse study which showed an inverse relation between the acute response of GTS-21 and other agonists and their delayed procognitive effects. I will try and locate it, but if I recall correctly, GTS-21 didn't show maximum procognitive effects until 18 hours after administration. 

Edited by bossmanglb, 03 July 2016 - 07:20 PM.

[bossmanglb]

Found it. Sorry it was macaques! Which is probably an even better translated model. 

 

Agonistsof nicotinic acetylcholine receptors (nAChRs) produce long-lasting cognitive effects in animal models and humans. The duration of these cognitive effects can outlast the presence of the agonists in the system, and the persistence of cognitive enhancement is increased further by repeated exposure. The basis for this discrepancy appears be the cellular and systemic mechanisms of learning and memory. Agonists of nAChRs induce long-term potentiation (LTP), which is a strengthening of synaptic connections that is associated with learning and memory formation. Some of the cellular effects of nAChR agonists overlap with the known cellular mechanisms of LTP, including long-lasting increases in intracellular concentrations of Ca2+, activation of second-messenger systems and transcription factors, elevated levels of gene products and enhanced neurotransmitter release. A better understanding of this phenomenon might shed new light on the role of nAChR systems in memory formation and retrieval.

→ source (external link)

 

I think this is an especially important paper for understanding a7 agonists. Inter alia,  it advances the topic of pharmacodynamic/pharmacokinetic discordance.

 

 

Traditionally, it has been assumed that the biochemical

and physiological effects (pharmacodynamics) of a drug

depend directly on the concentration of the drug at the site

of action over time (pharmacokinetics). However, for many

drugs that act on the CNS, there are instances when peak

blood levels do not correlate with peak clinical efficacy.

 

Table 2 ranks the effectiveness

of eight cognition-enhancing agents that have been

evaluated under similar conditions to the nAChR agonists

in Table 1. In general, there is an inverse relationship

between the magnitude of the initial response and that of 

the protracted response for both nAChR agonists and

drugs from other classes. This indicates that acute

responses in behavioral tasks that are designed to

estimate improvements in memory might underestimate

the true potential of many compounds.

 

 

 

Images and paper attached. I don't seem to be able to upload the table images directly here unfortunately. 

If someone else knows how, please feel free. 

 

 

 

 

 

 

 

Attached Files

•  Long-lasting_cognitive_improvement_with_nAChr_agonists_Buccafusco2005.pdf   225.75KB   6 downloads
•  GTS delay -- Buccafusco.png   60.39KB   1 downloads
•  GTS delay table 2 --buccafusco.png   40.82KB   1 downloads

Edited by bossmanglb, 03 July 2016 - 08:57 PM.

[bossmanglb]

What's GTS effects on the liver and kidneys?

a7 receptors are indeed found throughout the body. 

In this respect, it seems GTS and other a7 agonists exhibit an antinflammatory action via macrophages, I believe. 

 

In the original study attached to the inaugural post here, there was a transient elevation in liver enzymes for at least one participant. 

I believe he dropped out. 

[bossmanglb]

Here is an additional study looking into some more of the atypical, downright paradoxical responses of nicotinic a7 agonists. 

Nota bene:  DMXB-A = GTS-21

 

I'm still digesting all this, and unsure how to harmonize it all. But I wanted to bring it to the community's attention in hopes 

that we can get a better understanding of this receptor subtype and what exactly this class of compounds is doing. 

 

 

Attached Files

•  a7 Nicotinic Receptor Agonist_ is less more_buchanan2011.pdf   96.93KB   12 downloads

[Heisenburger]

So is there any continued interest in this substance? I’m getting ready to place an order with HHD and can obtain more GTS-21 if there is demand for it. At HHD’s current price, the best I can offer at this time is $30/gram, First Class shipping included. That would be slower than Priority, but at least they now provide tracking, which they didn’t in the past. That price would be double what I was charging the first time around when I was selling it to everybody for cost, but it is still substantially less expensive than reChem’s price, which is $35/gram, and only if you buy five grams. Their single-gram price is $60. They also charge about $14 for shipping, and take a considerable amount of time to fill orders. So if anybody is still interested, let me know, and if I get enough favorable responses/interest I will go ahead and place the order. It is very possible that I can drop the price in the future if HHD’s bulk prices go down (they fluctuate considerably) and if sales are heavy enough to warrant purchasing in larger quantities.  HHD has also now started distributing Dihexa, and I am considering buying a small amount to sell on a trial basis. The price would most likely be in the $100/gram range. If there is any interest expressed in this compound, I will obtain it.

[Reformed-Redan]

So is there any continued interest in this substance? I’m getting ready to place an order with HHD and can obtain more GTS-21 if there is demand for it. At HHD’s current price, the best I can offer at this time is $30/gram, First Class shipping included. That would be slower than Priority, but at least they now provide tracking, which they didn’t in the past. That price would be double what I was charging the first time around when I was selling it to everybody for cost, but it is still substantially less expensive than reChem’s price, which is $35/gram, and only if you buy five grams. Their single-gram price is $60. They also charge about $14 for shipping, and take a considerable amount of time to fill orders. So if anybody is still interested, let me know, and if I get enough favorable responses/interest I will go ahead and place the order. It is very possible that I can drop the price in the future if HHD’s bulk prices go down (they fluctuate considerably) and if sales are heavy enough to warrant purchasing in larger quantities.  HHD has also now started distributing Dihexa, and I am considering buying a small amount to sell on a trial basis. The price would most likely be in the $100/gram range. If there is any interest expressed in this compound, I will obtain it.

 

 

Hi Heisenburger,

 

I've noticed HHD charging higher prices for nootropics in the past. Maybe you could get some nootropic suppliers like vosunnootropic on board? They have unbeatable prices...

 

I'd be interested in trialing this compound again for ADD-PI and depression.

Edited by redan, 11 August 2016 - 07:07 PM.

[Reformed-Redan]

Here is their contact info:

 

http://www.vosunnoot...g-en/contact-us

[Heisenburger]

I'd be interested in trialing this compound again for ADD-PI and depression.

 

What sort of results did you get the first time around?

[Reformed-Redan]

 

I'd be interested in trialing this compound again for ADD-PI and depression.

 

What sort of results did you get the first time around?

 

 

 

It's hard to say, as I was taking a lot of other stuff. I suppose what I noticed most prominently was a sort of quieting down of everything in my mind. Wasn't as distracted by things... I guess this is in line with the channel gating properties of GTS-21. In some ways it felt like Nefiracetam (have you tried it?) but without the numbing out of everything that I feel with Nefiracetam.

 

Would have to try again to focus on the effects and try and put them down in paper. At least I know nothing bad happened apart from the burning sensation from the GTS-21 in my mouth.

Edited by redan, 11 August 2016 - 08:37 PM.

[Heisenburger]

At least I know nothing bad happened apart from the burning sensation from the GTS-21 in my mouth.

 

I’ll give you a tip: that stuff dissolves instantly in water, even cold water. Just stir it into a few ounces of the refreshing beverage of your choice, and you won’t have to contend with the burn.

[dwaaam]

So is there any continued interest in this substance? I’m getting ready to place an order with HHD and can obtain more GTS-21 if there is demand for it. At HHD’s current price, the best I can offer at this time is $30/gram, First Class shipping included. That would be slower than Priority, but at least they now provide tracking, which they didn’t in the past. That price would be double what I was charging the first time around when I was selling it to everybody for cost, but it is still substantially less expensive than reChem’s price, which is $35/gram, and only if you buy five grams. Their single-gram price is $60. They also charge about $14 for shipping, and take a considerable amount of time to fill orders. So if anybody is still interested, let me know, and if I get enough favorable responses/interest I will go ahead and place the order. It is very possible that I can drop the price in the future if HHD’s bulk prices go down (they fluctuate considerably) and if sales are heavy enough to warrant purchasing in larger quantities.  HHD has also now started distributing Dihexa, and I am considering buying a small amount to sell on a trial basis. The price would most likely be in the $100/gram range. If there is any interest expressed in this compound, I will obtain it.

 

I am very interested in Dihexa! Does HHD offer any third party analysis of their product or do you have to arrange that yourself? If I remember correctly you redistributed the GTS-21 without doing any analysis?

For GTS-21, atleast you know if you have the correct product, because of its corrosive and staining nature of the substance. Even if you do not know the purity. But with Dihexa, it should be an inert white powder. So more difficult to asses if it is the correct product.

But we could trust in HHD's reputation though, atleast it seemed to be legit GTS-21.

[Heisenburger]

For GTS-21, atleast you know if you have the correct product, because of its corrosive and staining nature of the substance. Even if you do not know the purity. But with Dihexa, it should be an inert white powder. So more difficult to asses if it is the correct product.

But we could trust in HHD's reputation though, atleast it seemed to be legit GTS-21.

 

 

You took the words right out of my mouth. I’m still debating what to do about this. Tianeptine and GTS-21 both lend themselves easily to organoleptic analysis, as you correctly pointed out. The psychoactive properties of the former and the unusual appearance and acidity of the latter are unmistakable. However, this can not be said of Dihexa. I’m not sure how I’m going to resolve this issue. As usual, I’m open to suggestions.

[Heisenburger]

HHD is also offering me purity options. For example, if I want some right now, they said they will send some stuff that tests out at about 95% purity for $450/10 grams. But they also told me that if I want to wait a month, they will have some stuff which tests as 98% purity for $600/10 grams. So that complicates matters even further. Whichever way I decide to go, I’ll make as detailed a disclosure on the eBay listing as I possibly can, including everything I’ve already mentioned and whether or not I had it sent out for analysis, and if so, to whom.

[Major Legend]

This stuff gets everywhere, so far no effects at 100mg, should I raise it to 150mg or even 200mg (is this safe?), I also have punishing anxiety so I haven't felt anything on that either. If there is a stimulatory effect its certainly not strong enough to be very noticeable.

[Reformed-Redan]

HHD is also offering me purity options. For example, if I want some right now, they said they will send some stuff that tests out at about 95% purity for $450/10 grams. But they also told me that if I want to wait a month, they will have some stuff which tests as 98% purity for $600/10 grams. So that complicates matters even further. Whichever way I decide to go, I’ll make as detailed a disclosure on the eBay listing as I possibly can, including everything I’ve already mentioned and whether or not I had it sent out for analysis, and if so, to whom.

 

 

Those prices are outrageous. 

 

We really need to find another supplier willing to synthesize this compound to drive down costs, IMO. 

[Heisenburger]

We really need to find another supplier willing to synthesize this compound to drive down costs, IMO.

 

Right, it’s just a polypeptide, isn’t it? Aren’t those ridiculously easy to synthesize? Even 30 years ago, Durk Pearson mentioned in his first book that small Japanese tabletop amino acid sequencers were only about $3000. Wouldn’t making Dihexa be something that just about anybody—even someone with a limited education in the chemical sciences, pull off? Forgive me if this is an ignorant and/or naïve question—I don’t know much about protein synthesis beyond just the most basic concepts.

 

[Reformed-Redan]

If you want I can start sending custom synthesis requests. I know a few labs that might be able to help and at a competitive price. 

 

I mean, we might as well do that in the free time. The more suppliers the merrier. 

[Heisenburger]

Go for it and report back. Meanwhile, maybe I'll contact other Chinese suppliers and see what they have to offer.

[Heisenburger]

I have GTS-21 on hand now, if there is still any interest. The price is $32/gram, shipping included. Steep, I know—but still substantially less expensive than the scant few other sources of this substance. I am actively looking for a less pricey bulk supplier, but bulk suppliers are about as common as consumer-level sources for this particular novel molecule. But I will keep trying. If interested, please contact me through the board.

[Water Buffalo]

Here is an additional study looking into some more of the atypical, downright paradoxical responses of nicotinic a7 agonists. 

Nota bene:  DMXB-A = GTS-21

 

I'm still digesting all this, and unsure how to harmonize it all. But I wanted to bring it to the community's attention in hopes 

that we can get a better understanding of this receptor subtype and what exactly this class of compounds is doing. 

 

Just to beat a dead horse to death, the failure of the last GTS-21 study on schizophrenic patients using 150 mg 2x/day leads me to believe that sticking to the OP study would be in our best interests. I thought that the failure of GTS-21 to significantly improve cognition, but not negative symptoms, was due to the reduced amount of a7 nicotinic receptors in the brains of schizophrenics. The author of this review didn't mention that as a potential cause for the lack of effects on cognition. 25 mg 3x/day might be a hassle to take in a capsule everyday, but we know that it's effective.

[Reformed-Redan]

So, since this product is much more popular and more people are interested in it, the prices have substantially gone down.

 

I received this quote today:

 

Hello S

Thanks for your inquirying!

We specialised in API raw material, especially used for researching. About GTS-21, for 100g, the best price is usd 855 including shipping costs.

Please confirm ok and let me know if you have any problems, thanks!

Wishing for your replying!

Best Regards 
Rebecca Lee

From:

 

https://tgybio.en.al....1a7c3e5fos9WtF

 

I am willing to put up 400 USD. The rest is for you to split part.

 

Best regards.

[Forever21]

Group buy. I'm interesrsted.