199 replies to this topic

[KoolK3n]

GEBR-7b is a highly selective PDE4D inhibitor. In recent studies, it's been shown to enhance memory. It boosts extracellular levels of cAMP in the hippocampus of up to 40%. Unlike Rolipram, it doesn't cause emesis at memory enhancing doses. And it's also 3-10x more potent than Rolipram. More info can be found here: http://www.ncbi.nlm....les/PMC3246667/.

The best part is while GEBR-7b is a research chemical, it is cheaper than the traditional CILTEP stack (Forskolin, Zembrin, Artichoke).

This American (Not Chinese) company can synthesize 5mg of GEBR-7b for $100. The optimal dosage in rats is .001mg/kg-.003mg/kg. So for a human weighing 80kg, that would be between .006mg-.018mg/d. At the highest positive dose used every day, 5mg would last 277 days. Here is the manufacturer: http://www.millipore...item/524748-5mg. We could negotiate a price drop if we group buy this thing. 277 days is a long time so if you wanted to only experiment with it for only ~5 months, you could split it with someone and pay $50 instead of $100. What do you guys think?

One downside is that GEBR-7b is administered through injection. So a syringe/needle, bacteriostatic water, and vials will be required for trialing. Researchers in the study linked above only tested for object recognition and spatial memory. So other forms of memory weren't considered.

Edited by KoolK3n, 24 July 2013 - 12:24 AM.

[Spinlock]

I don't know how one would even measure 0.018mg other than by dumb luck that is the mass of one grain. Even then separating it would be difficult.

[KoolK3n]

I don't know how one would even measure 0.018mg other than by dumb luck that is the mass of one grain. Even then separating it would be difficult.

It'll come in a vial. That way you can extract and dilute the solution in another vial w/bacteriostatic water. I'll have to research this topic more in depth but it can definitely work out. But actually I messed up the calculation. I was extrapolating the converter dosage from animals to humans wrong. I was using mice. I needed to use rats like the study used. Unfortunately, using rats, the dosage requirements in humans goes up 100%. So instead of 277 days. At .036mg/d, it'll last roughly 130-140 days. That's still a good price even without the group buy price drop.

Edited by KoolK3n, 24 July 2013 - 01:45 AM.

[researchist]

http://www.jci.org/articles/view/22831 "rolipram ameliorates deficits in both long-term potentiation (LTP) and contextual learning". In this rolipram enhances other areas of learning, maybe this will be similar. I wonder if there would be an advantage to adding a dopamine precursor like phenylalanine as in CILTEP, to feed the dopamine synthesis which must be happening, when researching this compound?

[KoolK3n]

http://www.jci.org/articles/view/22831 "rolipram ameliorates deficits in both long-term potentiation (LTP) and contextual learning". In this rolipram enhances other areas of learning, maybe this will be similar. I wonder if there would be an advantage to adding a dopamine precursor like phenylalanine as in CILTEP, to feed the dopamine synthesis which must be happening, when researching this compound?

I doubt it'll make any difference or have any interaction with either Rolipram or GEBR-7b. Keep in mind selective PDE4D inhibition is generally limited to the hippocampus and probably the prefrontal cortex. I'm not too sure but I don't think dopamine enhancement in those areas are what we want compared to enhancement in the VTA. Thanks for the link though. Just reading it makes me want it more. Even if the effects successfully translate over to humans, this isn't "NZT". It'd still need to be stacked with other things. Imagine it stacked with an SSRI and/or NSI-189 (if it works). Hippocampus on steroids? I think so.

[researchist]

http://www.plosone.o...al.pone.0002558 I had heard that the reason some of these antidepressants work is they stimulate neurite outgrowth in the hippocampus. So we are happy when neurons are poppin and when they are not we are not, we cant think right either. I had been wondering which SSRI's had this effect. This says luvox does this but not paxil or Zoloft. I would like to get some NS-189 but luvox is cheaper. It sounded like dihexa might be the greatest ngf agonist possible. I think that if rolipram affects contextual learning it must be affecting a different area that the hippocampus but not totally sure. Something that is really good would need something stacked that enhances focus also like they say in ciltep. Maybe it wouldn't need a strong stimulant, maybe vincamine, PEA or coffee..

[megatron]

I don't really think this is such a good idea, as with C16 PKR Inhibitor. It's way too easy to overdose.

Edited by Megatrone, 25 July 2013 - 04:20 PM.

[KoolK3n]

http://www.plosone.o...al.pone.0002558 I had heard that the reason some of these antidepressants work is they stimulate neurite outgrowth in the hippocampus. So we are happy when neurons are poppin and when they are not we are not, we cant think right either. I had been wondering which SSRI's had this effect. This says luvox does this but not paxil or Zoloft. I would like to get some NS-189 but luvox is cheaper. It sounded like dihexa might be the greatest ngf agonist possible. I think that if rolipram affects contextual learning it must be affecting a different area that the hippocampus but not totally sure. Something that is really good would need something stacked that enhances focus also like they say in ciltep. Maybe it wouldn't need a strong stimulant, maybe vincamine, PEA or coffee..

That's very interesting. It seems like some SSRIs promote neurogenesis through different pathways. See here: http://www.ncbi.nlm....les/PMC3121947/. I don't want to derail this thread too much but for focus I'm gonna be experimenting with Metadoxine and Phosphatidylserine.

[KoolK3n]

I don't really think this is such a good idea, as with C16 PKR Inhibitor. It's way too easy to overdose.

I definitely agree. Maybe someone who's more experienced in the field can safely collect, measure, and dispense it to group buy participants. I'd imagine some sort of compensation though. We're dealing with 36ug. Vitamin b12 RDA is 2.4ug. So its not as small as one would think.

Edited by KoolK3n, 25 July 2013 - 04:46 PM.

[researchist]

Hopefully someone would not actually stack things with an unknown compound they were researching. We were conjecturing about possibilities, I think. I was interested in taking part in a group buy of this. The injection puts me off a bit. I'm a little lost about your reference to illicit drugs. Are you thinking about whether the microgram dosage is correct or you think it might not contain the compound you are expecting. The dosage is very small. Active dosage of ngf would be very small too. That would be an interesting substance. I don't think you can overdose on that. What happened with C16? That seems like an a compound with incredible possibilities.

[KoolK3n]

Hopefully someone would not actually stack things with an unknown compound they were researching. We were conjecturing about possibilities, I think. I was interested in taking part in a group buy of this. The injection puts me off a bit. I'm a little lost about your reference to illicit drugs. Are you thinking about whether the microgram dosage is correct or you think it might not contain the compound you are expecting. The dosage is very small. Active dosage of ngf would be very small too. That would be an interesting substance. I don't think you can overdose on that. What happened with C16? That seems like an a compound with incredible possibilities.

I asked googlotarian (spelled wrong) what the situation was. He said he hasn't had time but in two weeks things should get moving again. I understand if injection is unappealing to you. But it is my intention to stack it starting at the lowest dose possible then slowly titrating it up to .036mg. Were you suggesting Rolipram be labeled as "unknown compound"? Or just GEBR-7b?

[researchist]

I can deal with the injection. There are a lot of things which can only be administered that way. I've never thought an injection was the high point of my day. I'm considering at least in the beginning that GEBR-7b is a largely unknown substance. I have a program of daily supplements, vitamins, nootropics of various kinds. When looking to try a new substances the thing I'm most careful with is MAO. That's something to really be careful with. I was more concerned with starting out and stacking a new substance with something like NS-189 and a stimulant etc, might not be too wise until it was determined that there were no reactions to the new substance. I'm not taking anything that worries me too much. I think titrating upward incrementally is the best way. How low were you thinking is lowest possible? Smallest you can measure in an insulin syringe? The mixture proportions will be important so that your .036 highest dosage is as small an amount of water as can be while making it dilute enough to be able to see a small increment difference on the scale. What about GEBR-7b for long term memory. NS-189 for neuron growth and PRL-8-147 to increase working memory and a stimulant..

Edited by researchist, 25 July 2013 - 06:06 PM.

[KoolK3n]

Smallest you can measure in an insulin syringe?

Yeah. I'd only include participants who know what there dealing with and understand the risks involved.

What about GEBR-7b for long term memory. NS-189 for neuron growth and PRL-8-147 to increase working memory and a stimulant..

Its all theoretical especially since we're dealing with research chemicals. I'm trying to avoid any sort of stimulant if possible.

[researchist]

Something like this seems to balance these concerns (amount of liquid per injection) * (ease of reading graduations) * (ease of mixing quantity)
30 *.01cc - 3/10 ml insulin syringe
20*.01cc== 36microgram
180micrograms per ML
10*.01cc== 18microgram
5*.01cc == 9microgram
1*.01cc == 1.8microgram

Edited by researchist, 25 July 2013 - 09:27 PM.

[KoolK3n]

Something like this seems to balance these concerns (amount of liquid per injection) * (ease of reading graduations) * (ease of mixing quantity)
30 cc - 3/10 ml insulin syringe
20cc == 36microgram
180micrograms per ML
10cc == 18microgram
5cc == 9microgram
1cc == 1.8microgram

20cc is quite a lot. I was thinking of 1cc per "serving size". If the vial is 10mL containing 5mg. 1mL will hold almost two weeks worth (13.88 days) of GEBR-7b. Dilute that in a vial with 13mL bacteriostatic water. Total volume will be at 14mL. Administer 1mL once daily. I'm not sure if once daily is sufficient because Rolipram has a short half life. Or we could that even further. So have a vial with 12mL bacteriostatic water and 2mL of GEBR-7b, then administer .5mL once daily. And oops EMD Millipore (supplier) is located in Germany. Not USA :P sorry.

Edited by KoolK3n, 25 July 2013 - 09:26 PM.

[researchist]

So what I call a CC is a tick mark. I mean .01 cc. A cc is 1ml. So this comes out fairly nicely if you look at it that way. I didn't look it over before I submitted it. Lucky there is edit 30 tick marks - 3/10 ml insulin syringe
20 tick marks== 36microgram
180micrograms per ML
10 tick marks== 18microgram
5 tick marks == 9microgram
1 tick marks == 1.8microgram

Edited by researchist, 25 July 2013 - 09:32 PM.

[researchist]

So that is close except I took into account the high end that you were saying 36 micrograms which would be 20 ticks but you could start with 1 tick which is 1.8 microgram. Noi saying you have to. Just an idea. So this would account for it not being a fixed dose and would allow it to be easily titrated upward.

[starmon]

you could try and lay it on blotter paper

[KoolK3n]

So that is close except I took into account the high end that you were saying 36 micrograms which would be 20 ticks but you could start with 1 tick which is 1.8 microgram. Noi saying you have to. Just an idea. So this would account for it not being a fixed dose and would allow it to be easily titrated upward.

Oh-ok. I didn't know you were talking about incremental titration.

you could try and lay it on blotter paper

You mean like sublingually? Because that method hasn't been tested yet. I wonder if transdermal DMSO could be an alternative to injecting.

[researchist]

Yeah, I think it through but don't always get it down like I'm thinking. Starmon should get the prize for administration suggestions though, with a tried and true technology. It's getting to seem like something illicit is going on here

[researchist]

I don't think it absorbs orally or can be digested. So blotter wouldn't work. Maybe a nasal spray might? I would go with what the studies say though.

[researchist]

It is interesting that they have this compound as a catalog item. Has anyone made an inquiry of Millipore. This I believe is a Merck company. Tocris has some interesting compounds in their catalog, one I believe is ISX-9. Somewhere on these forums I read that Tocris has stringent standards in that a research organization must meet in order to purchase from them. Some companies are more or less stringent in terms of requirements. Is this a possible issue?

[KoolK3n]

I honestly don't have any idea sorry. I do agree with you though that ISRB/C16 is the most exciting RC right now. I'm also eager to hear the results of NSI-189 both from phase 1b and longecity members. BPAP included. But if GEBR-7b is only an analog to Rolipram, the anticipated effects should be the most reliable (most studied) out of all of our current chemical involvements. GEBR-7b could also replace the CILTEP stack and I'm surprised no one is interested in exploring other PDE4 inhibitors like this one. GEBR-7b/Rolipram has far more extensive research behind it than Kanna (Zembrin) and Artichoke. So yeah GEBR-7b may not dramatically be the life changing drug we need but it is the most reliable in its purported mechanism of action and hence could be an effective add-on it a comprehensive stack.

[researchist]

It just seemed surprising it was in their catalog rather than custom synthesis. There has to be some lively research going on with this for them to invest in making it in bulk, I think. Though there only seems to be one study on GEBR-7b. I noticed this link on the page the study you cited above. http://www.ncbi.nlm....pubmed/15672274. Effects of the novel PDE4 inhibitors MEM1018 and MEM1091. Different compounds same mechanism. On the same page as the last one http://www.ncbi.nlm....pubmed/22832854. PDE4 inhibition enhances hippocampal synaptic plasticity in vivo and rescues MK801-induced impairment of long-term potentiation and object recognition memory in an animal model of psychosis. The PDE4 inhibitors have positive effects on memory, and there has been a lot of study. GEBR-7b seems to be the newest and possibly most powerful one so far and don't forget not emetic.

[researchist]

Selective phosphodiesterase inhibitors: a promising target for cognition enhancement http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2704616/ PDE and healthy subjects - http://clinicaltrial...how/NCT01433666

[KoolK3n]

Now it is my intention to eventually test it out but if we don't get a group buy going. I won't bother with it (due to variety of reasons) until school is out again (c.a. 8 months). To anyone reading this can you at least post that you MIGHT be interested in the group buy? That would help a lot because so far the discussion on this thread has been largely underwhelming. I'm not talking about you researchist don't worry.

Edited by KoolK3n, 27 July 2013 - 12:27 AM.

[PWAIN]

I might be interested but not if it requires injection.

[KoolK3n]

I might be interested but not if it requires injection.

Totally understandable. You could test out a transdermal approach using DMSO.

Interesting read: http://link.springer...1/fulltext.html

[PWAIN]

Like to better understand the feasibility of this working before chucking a bunch of money at it. What is the general feeling around here about this approach working?

[KoolK3n]

Like to better understand the feasibility of this working

Wouldn't we all? Your statement can be applied to ALL current group buy projects. I personally believe though that GEBR-7b/Rolipram has the most research behind it. Actually I don't personally believe, it is fact that it has the most. The total amount of data on it compared to PRL, NSI, BPAP, ISRIB, IRDA COMBINED is still 10 to 1. DMSO will permeate ANYTHING through the skin and into the body.