# bbb & GABA



## shontay (Mar 1, 2007)

GABA can't pass the bbb on its own. I have a little more complex question that maybe some of you chemies, or bbb experienced can help me with. i've read many articles about the bbb, and i'm still pretty confused (not the sharpest tool in the shed). it would seem that with a transporter (from what i've read, a transporter has the ability to allow a chemical that wouldn't on its own pass the bbb to get through) GABA could pass this bbb. my thought was mixing GABA powder with 50% ethyl oleate (two purposes-a transporter, and it will aid in the combining of GABA and olive oil to make a solution with the assistance of heat), and olive oil. heat the mixture until it becomes a solution then filter with a .22 micron filter. Depending on the amount of GABA added, this will produce an injectable solution with ?mg/ml. 

ok the question. if administered IM, does this solution have any chance to pass the bbb. if so, what is the highest % i can expect to pass?

thanks,
shontay

btw, I’m currently on 4mg clonazapam and 20mg adderall per day for social anxiety. It took me a year to convince a dr to prescribe this somewhat non-conventional combination for only social anxiety. To make a long story short, I’m the happiest I’ve been in my life, and hate that I waited so long to get help. Now that I have a known cure, I’d like to see if I can lower or even eliminate my clonazapam. Then work on a better solution for the adderall.


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## korey (Apr 25, 2006)

*Re: bbb @ GABA*

You seem to have a fairly good grip on the chemistry of your experiment (probably a much firmer grip than me :cry I'm just a teeny first semester organic chemistry student), but if you look into the biology/neurophysiology of what you're proposing, you'll probably find that no matter how much GABA you manage to cram into your brain, you won't be able to actually utilize it the way you're wanting without an MAOI or an outside source of GABA uptake inhibition, like a benzo or a barbiturate. Something extra has to be there to facilitate the GABA to do what you want it to do. Granted, this is only what I've gathered from reading a few Google results on the subject, but it seems to make sense.

At any rate, I don't think it's safe for you to inject yourself with a potion you cook up in your chem lab (or kitchen :b). If you absolutely must experience the results for yourself, then take the product orally (add some kind of flavoring if you must). If your reaction goes awry, you could end up injecting yourself with something lethal.

I mentioned my little Google stint a second ago. Your thread reminded me of that stuff called Picamilon. It's a chemical that originated in Russia (I think?) as a drug for treating brain trauma or something. Don't you just love how thorough and specific I'm being? Anyway, Picamilon is simply a synthesis of GABA and Vitamin B3. The B3 acts as the transporter in this compound by increasing neurovascular circulation (I think?), which increases GABA's clearance across the BBB. I have this fun program called ChemDraw by CambridgeSoft, and it lets me draw chemical structures and reactions very easily. I figured you might be interested in seeing the reaction (chemicals only; I have no idea about the catalysts, but you can probably think of one that would give a reasonable reaction mechanism to yield the product...elimination/dehydration, maybe? I don't know. I haven't worked with amino acids yet).

The product is the pure acid. Picamilon is said to be a sodium salt of the product acid, so that's something else to consider.

On a side note, I also take a benzo and a stimulant, and I find that they work great together (and they definitely don't cancel each other out as most seem to think). As you can probably see in my signature, the stimulant I'm taking is Dexedrine. It's okay, but I actually miss the peripheral stimulation that racemic ol' Adderall gave me. It was not only a physical boost, but it also helped me monitor my dose (i.e, too much = unusually fast heart beat, vascular headache after metabolism, etc; too little = no energy, lethargic, difficult to think clearly or concentrate (basically everything I experienced on a daily basis from the time I started lithium and Xanax until the time I started treatment with stimulants), etc). With Dexedrine, it's practically pure CNS stimulation without the peripheral effects, so if I take too little or too much, then that's just too bad for me. When I took my first dose of it last week (or the week before?), I think I stayed awake all night long with an immense desire to get things done and no desire to sleep. It was a funny experience, but after day 2 of that, I realized that I was going to have to change something. If I adjust to the Dexedrine over the next month, then I'll continue with it. If not, I might see about returning to Adderall.

Hope you enjoy my sad little graphic!


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## shontay (Mar 1, 2007)

awesome response Korey. 

i understand what you are saying about flooding the brain with GABA and having no receptors to receive it=waste of time. since i'm new to all this, i may be wrong, but doesn't theanine, and like you mentioned, picamilon work on the same basis i'm proposing (just using a transport to increase GABA)? if this is true, then these chemicals will only have a positive effect on people who's brain doesn’t make enough GABA available. 

in my case, i'm taking adderall. if i'm not mistaken, this is a MAOI acting stimulant. because it's a MAOI, wouldn't it be a GABA inhibitor?

thanks for the response, i've learned a lot in just those few line.

shontay


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## X33 (Feb 13, 2005)

Picamilon, then is quite similar to Phenibut. Both have phenyl groups attached to GABA. There are differences like the position of the ring and the substituents on the ring. Overall though, to me (not an expert) they seem pretty close structure-wise. Do they have similar activity?

Phenibut:
http://en.wikipedia.org/wiki/Imagehenibut.png


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## X33 (Feb 13, 2005)

shontay said:


> GABA can't pass the bbb on its own. I have a little more complex question that maybe some of you chemies, or bbb experienced can help me with. i've read many articles about the bbb, and i'm still pretty confused (not the sharpest tool in the shed). it would seem that with a transporter (from what i've read, a transporter has the ability to allow a chemical that wouldn't on its own pass the bbb to get through) GABA could pass this bbb. my thought was mixing GABA powder with *50% ethyl oleate (two purposes-a transporter, and it will aid in the combining of GABA and olive oil to make a solution with the assistance of heat), and olive oil.* heat the mixture until it becomes a solution then filter with a .22 micron filter. Depending on the amount of GABA added, this will produce an injectable solution with ?mg/ml.
> 
> ok the question. if administered IM, does this solution have any chance to pass the bbb. if so, what is the highest % i can expect to pass?
> 
> ...


WAIT!! How is ethyl oleate a transporter? I read briefly about it on Wikipedia (http://en.wikipedia.org/wiki/Ethyl_oleate).

Ethyl oleate is a combination of ethanol and oleic acid (a fatty acid - found in olive oil, I think). It is used by pharmaceutical companies to dissolve hydrophobic/oily substances. I don't see how it would help in the uptake of GABA (a hydrophillic/water soluble substance) by the brain. Please explain.

And as Korey said, you definitely don't want to inject homemade stuff into your body! That sounds dangerous.

EDIT: And as far as I know, transporters are proteins inserted into cell membranes. They take stuff from one side and dump it into the other side. There are variations i.e. they can also be channels which allow stuff to go through.

Unfortunately, there is no way you can add a (say a GABA) transporter to your blood brain barrier (maybe with gene therapy but we are not there yet). So the only way to get anything across the bbb is by changing the "thing" so that it can get across on its own (make it soluble in the cell membranes, which are hydrophobic/oily).

GABA related products which do this are phenibut, picamilon etc.


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## shontay (Mar 1, 2007)

hey ag,

i'll look up a reference to EO, oils, and simple sugars as being transporters through the bbb. there are many docs that state this, at least from the way i interpret them. it would help if the darn smart *** chemy engineers (or whatever they are) would write in english so this dumb *** elect eng can follow. it's funny because they make even the simplest statement sound complex and meaningful. i bet they could make the statement "i just scratched my balls" so complex it would take me half an hour to comprehend. i understand the concept and importance of technical writing, but come on. wow, that was a major tangent. 

basically what i'm trying to do is use EO and an oil as a bbb transporter for GABA, much the same way as picamilon and theanine use transporters. if EO and oil pass GABA through the bbb, my thought is the GABA level passing the bbb is more easily controlled, and a much lower GABA dose is necessary compared to picamilon or theanine is necessary (because of the delivery method and solution control). 

from my little knowledge and experience (ethyl oleate can not be taken orally, some may relate to my experience with this ). 

hey korey,
i wish i had the brain of a first semester chem major. hell i'd settle for the brain i had 20 years ago. i'm going to look into benzos, and the MAOI nardil in hopes of understanding how to effect GABA uptake inhibition (opening GABA receptors-same thing right?). can you offer any advice or point me in the right direction?

shontay


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## X33 (Feb 13, 2005)

shontay you may be right. I thought about it a bit more. When you add GABA to ethyl oleate and then heat the mixture, do you get a combination product? 

Maybe something like this?

GABA:ethanolleic acid

If this is the product you get, then it should be able to pass the bbb much like phenibut, picamilon because it has the 18 carbon saturated tail of oleic acid, which should provide enough hydrophobicity for the compound to enter the cell.


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## shontay (Mar 1, 2007)

hey Korey,

GABA is an agonist to the GABA neurotransmitters GABAa-c. so it works in the same was as barbiturates and benzos on them.


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## korey (Apr 25, 2006)

shontay said:


> i understand what you are saying about flooding the brain with GABA and having no receptors to receive it=waste of time. since i'm new to all this, i may be wrong, but doesn't theanine, and like you mentioned, picamilon work on the same basis i'm proposing (just using a transport to increase GABA)? if this is true, then these chemicals will only have a positive effect on people who's brain doesn't make enough GABA available.


I would think that your proposed compounding of GABA with a fatty acid would give results similar to those of Picamilon, but to be honest, I really can't say for sure. I don't know if anyone can actually say for sure, but I'm guessing that cramming synthetic GABA into your brain would eventually cause some anxiolytic reaction due to so much of it being there. I read a few Google bits about GABA the other day, and according to what I read, some of the structures in the brain are thought to allow small amounts of GABA into the brain when the body is flooded with GABA (i.e, when someone buys a bottle of GABA supplement and takes a ton of it). I don't think that'd be a very healthy or effective way of continually getting GABA past the BBB, though.



> in my case, i'm taking adderall. if i'm not mistaken, this is a MAOI acting stimulant. because it's a MAOI, wouldn't it be a GABA inhibitor?


I think amphetamine exhibits some MAO inhibition, but I don't know if it's selective enough to noticeably affect GABA.



shontay said:


> hey korey,
> i wish i had the brain of a first semester chem major. hell i'd settle for the brain i had 20 years ago. i'm going to look into benzos, and the MAOI nardil in hopes of understanding how to effect GABA uptake inhibition (opening GABA receptors-same thing right?). can you offer any advice or point me in the right direction?
> 
> shontay


I'm a pre-pharmacy major, not a chem major  Though, if I don't get accepted to pharmacy school, I just might have to become a chem major :um

I think uptake inhibition is forcing a neurotransmitter to remain in the receptors/at the receptor sites for longer amounts of time, but my understanding of that could be wrong.

MAOIs work by inhibiting (slowing) the metabolic breakdown of monoamine oxidase, which is the enzyme that breaks down neurochemicals. So if the breakdown of GABA is inhibited by an MAOI, then the GABA in the brain can increase and remain at the receptor sites longer. That's the general idea, I think.



shontay said:


> hey Korey,
> 
> GABA is an agonist to the GABA neurotransmitters GABAa-c. so it works in the same was as barbiturates and benzos on them.


(This is a technicality, but I think GABAa,b,&c are GABA receptors, not neurotransmitters. GABA itself is the neurotransmitter.)
As for a response to that - ok :b

Early today, I decided to look through my organic chemistry textbook for a reaction or a series of reactions that could possibly combine GABA with a fatty acid, but it occurred to me that even if I did find the right reactions to get a lipophilic version of GABA, I certainly don't know enough neurochemistry to tell if the brain even has the proper enzymes to turn the GABA+fatty acid compound back into just GABA and a fatty acid. If not, then it was just a failed experiment, but what if the fatty GABA (lol) were to cause some unpleasant reaction? There are compounds that are only an atom or two away from being GABA, yet they all impact the mind and body differently. For instance, GHB merely has a hydroxyl group where the amine is in GABA, yet GHB is and has been used as a surgical anesthetic. And that's just a difference of one functional group! :eek Is there a set of rules or something we could go by when determining which transporter is safe to use? :con


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## shontay (Mar 1, 2007)

hey Korey,

any chance i could get a copy of chemdraw from you? does it just allow you to draw the chemicals, or does it have a library of chemicals to choose from. also does it allow you to get the outcome from combined chemicals (like what your picture showed)?

Gaba is/can be organic. no issues with the use of fatty acids. EO and oil is often used (common practice) to transfer hormone powders that can't be digested into solutions for injection. like you, i believe the side effect of orally taking gaba to achive any level bbb could be toxic.

still have a long way to go, and think i'm missing something. plus need an ester like enanthate, to slow delivery (one injection a week, not one every 4 hours or howerver long the effects of gaba last).

you're right gaba is an agonist to the neurotransmitter GABAa-c recepters, but you knew what i meant.

shontay


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## korey (Apr 25, 2006)

shontay said:


> hey Korey,
> 
> any chance i could get a copy of chemdraw from you? does it just allow you to draw the chemicals, or does it have a library of chemicals to choose from. also does it allow you to get the outcome from combined chemicals (like what your picture showed)?
> 
> ...


The maker of the ChemDraw software (CambridgeSoft) offers a trial version of all its software available for download from its website. A trial version is the complete version with a programmed time limit, and programmed time limits can be easily overcome if you know where to look 

ChemDraw is basically like Photoshop, only it's exclusively for drawing chemicals. The Merck Index is what you would need for an exhaustive resource of chemicals, structures, names, properties, etc. There's usually a print copy of it in most large libraries (in the reference section), but there is a computerized version that comes with the print version (or you can order it separately). I noticed that my college's library's copy of the Merck Index had the CD of the computer version still in the back part of it with the serial number and everything. If you wanted, you could probably slip the CD into a bag, take it home and install it on your computer, and then return it back to the library without anyone having to know :yes But that's up to you, and I am in no way advocating the illicit use of copyrighted material ::safe:: :boogie

However, ChemDraw does not formulate chemical reactions for you. It's not as if you can draw the structures of some chemicals and then click a command that would tell you exactly how to combine those chemicals to form a certain product. ChemDraw is strictly an illustrator. It does know when a structure or name is incorrect, but it's not a downloadable organic chemistry professor (although, I'm sure there are plenty of downloadable organic chemistry books out there ) You have to know which chemicals you want to work with, and you have to know the organic reactions (and catalysts/reaction conditions would help :b) that would need to take place in order to yield the product you have in mind. Along with that, you need to know *all* of the products you'll be making in case one of them is toxic or otherwise unsafe. You pretty much have to know a book of organic chemical reactions along with the concepts behind them if you want to synthesize a new compound without accidentally making poison or something. Does that make sense? You're going to need to know every corner of the reaction. From what you've posted so far, you seem to be familiar with organic chemistry, but you seem to be lacking some essential knowledge regarding reaction mechanisms (though, I could easily be wrong about that)

Another technicality is that GABA is already organic, it's just not lipophilic. The overall goal here is obviously to find a way to make GABA lipophilic enough to easily cross the BBB. The question is which chemical would reasonably make GABA lipophilic, and then _how_ would we go about synthesizing it.

Based on all the different Google searches I've done, we're not the only people who are trying to find a practical way of turning GABA lipophilic. There are lots of theories and even test studies out there about the effectiveness of different GABA analogs.


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## shy1984 (Sep 5, 2007)

Please don't inject yourself with anything


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## Bandit6 (Oct 20, 2007)

shy1984 said:


> Please don't inject yourself with anything


I agree. You might inject bubbles, get infections or get in more much serious trouble than just mere anxiety. Raw food oil is supposed to go trough the digestive tract before getting into the bloodstream. Who knows what enzymes and liver does to it before it's allowed to enter.

Concerning this GABA and olive oil from the grocery store(totally unpure of the fatty acid you need) theory that sounds like mad science to me. I seriously doubt the 2 molecules can chemically bind(atomic level) together by heating with a home appliance. You'll only get a solution(simple mix of the 2 products, no chemical binding) at best...


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## korey (Apr 25, 2006)

http://wanglab.ucsd.edu/html/publicatio ... review.pdf

That was a pretty interesting read.

Also, http://www.orgsyn.org/ is a very good source of organic synthesis reactions (including structures, procedures, catalysts, conditions, reaction vessels, etc).

The only reason I can think of to explain why the perfect GABA analog (w/r to the components discussed in the above article) hasn't been found yet is ... we don't have the technology :con We can obviously tinker around with as many chemicals as we'd like, but there's not a way to accurately weigh the risks against the benefits of a proposed compound with any certainty (aside from test studies, which always seem to come with death statistics :afr). Not yet, at least.

Shontay, I would suggest that you not mess with any of this unless you are a pharmaceutical researcher or a chemical engineer or something. Drug design is done under controlled conditions, usually with the help of a team of colleagues and a fully-equipped lab. Unless you have those at your disposal, you are probably wasting your time and potentially putting yourself in danger.


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## shontay (Mar 1, 2007)

hey bandit6,

there is a very, very common practice of using olive oil (other oils) along with an esterized hormones. ofcoarse the addition of BA and filtration of the boiled solution all but eliminates any infection possibility. these hormones solutions are injected millions of times/day.

humm, so you don't think EO and GABA mixed in oil at a temp ~ boiling woun't bind and cause an oil solution? if this were the case, woudn't the combination actually be called a suspention and not a solution as you say?

korey, 
like you i've found lots of studies on this topic. unfortunately, most of the info i was interested in required $ to read the data. :-( like i said, i'm doing great right now. i just think there are better solution than taking benzos and amphetamines the rest of my life. with a little research, and the help of a knowledgeable chemical person, the worse that i can do is learn.


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## X33 (Feb 13, 2005)

There are drugs out there, which already do what you are trying to achieve (i.e. Phenibut, Picamilon etc.)


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## CoconutHolder (Oct 13, 2007)

Just wanted to put something out there. I was at a local natural foods store the other day and I heard the owner talking to someone about a product that helps a lot with anxiety. So I asked her about it. She said that it is a top seller there and works great. She even said she takes it every day. I am going to try it. It is a patented formula. It contains GABA and helps the neurotransmitter in the brain work better.

It is called "Anxiety Control 24" I haven't used it yet but next time I go there I am going to buy it and try it out. She said it doesn't make you tired or anything either.


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## X33 (Feb 13, 2005)

These are the ingredients in Anxiety Control 24 -

Magnesium
Vitamin B6
GABA
Glycine
Glutamine
Passion flower
(Some other herb powder)

ok, now my personal thoughts on some of the ingredients-

Magnesium and Vit B6 - I have been taking this combination for some time now and while it has not helped me anxiety wise, I can see it helping others.

GABA - This won't do a thing because it cannot get into your brain. Sorry.

Glycine - Your body makes this product on its own. If you are eating well (enough protein), you shouldn't need this in a supplement. An interesting fact, Glycine is an inhibitory neurotransmitter like GABA but it works in the brain stem.

Glutamine - Again, your body can make this on its own. Given a good diet, you should be ok.

Passion flower/herb - Dunno, might help.

Overall, the product seems to be of little value for anxiety sufferers, sorry.


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## CoconutHolder (Oct 13, 2007)

oh well she said it works and is a hit product there. sorry it wasn't much help to you.


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## X33 (Feb 13, 2005)

I have not taken it but going by the ingredients it sounds bunk. If people are noticing benefits then it is good but technically speaking I do not see it helping the vast majority of anxiety sufferers. just an opinion.


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## CoconutHolder (Oct 13, 2007)

I plan on giving it a shot and I'll let everyone know if it helps me or not. Mabey next week I'll get it. I get a lot of general anxiety and tension too so I'm going to give it a shot as I don't like taking benzos too much. I have a hard time putting stock in natural products for anxiety at all so it will be interesting to me to see if I notice any result.


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## X33 (Feb 13, 2005)

I am with you. I don't like benzos either (see my other post 'Ativan users' in meds section) but there is no alternative that works as well as benzos as far as I know.

Anyway, hope you get good results from it.


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## shontay (Mar 1, 2007)

there are other solutions. you just need a little organic chemistry knowledge. it's not just some wacked ideas i have, look at a few patents on the subject of GABA and bbb. GABA recepters GABAa-c can also be controlled so it's not just a matter of getting GABA past the bbb, but other chemicals can be added to make the GABA recepters selective. 

shontay


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## X33 (Feb 13, 2005)

ok last post I am going to make here. 

I am not suggesting in any way that your idea won't work or is "wacked." God knows where you picked that up from. What I am saying is that what you are trying to do is already done with several readily available products. 

btw, don't try to make assumptions about my knowledge on the subject.
(I have taken 3 undergrad organic chem. classes, 2 advanced undergrad organic chem classes, 1 undergrad and 1 medical biochem class.)


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## shontay (Mar 1, 2007)

come on ag,

i realize there are other chemicals that have effect on GABA receptors. Phenibut for on does, but i believe it only effects the GABA(b) receptor. Picamilon is pretty cool because i think it may effect all the GABA(a-c) receptors, plus it has the added bonus of a side kick (maybe not adderall, but still a stimulating effect), but i also believe it has the disadvantage of having a half life of less than a hour.

the idea of making GABA lipophilic and then bonding it with heptanoic acid, or any long acting ester isn't new and has great potential. if you have the time, please read the link below on GABA and BBB: ((http://www.freepatentsonline.com/505144 ... temming=on). within the article, there is mention of using such esters with GABA, but none of the actual examples show this bond.

with this info contained in the link, it now seems there is/will be the ability to directly influence the GABAa-c receptors (selectively), could have the ability to use a simple amino acid to cure what i'm now taking scheduled narcotics for. The IM injection are great because i'm already taking them, and with the enanthate or cypionate esters, only 1 shot a week is necessary and it provides a very stable delivery system (little yoyo effect).

are you familiar with HRT (hormone replacement therapy). Many men my age are prescribed testosterone enanthate to elevate their testosterone level to normal. testosterone by itself has a half life of a few hours, but with the added esters this HRT therapy is a once a week IM injection in a solution of oil.

i'm not going way out on a branch here. please read the article, i'm sure you can see the benefits. i'm just asking for help in the chemical bonding that would seem very easy to someone in your field of study.

i haven't assumed anyone's knowledge, and only stated the lack of my knowledge in organic chemistry. if i insulted you in any way it definitely wasn't intentional. i'm just looking for help, guidance, and to learn.

your help is greatly appreciated.

shontay


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## X33 (Feb 13, 2005)

It's ok. I didn't like the fact that you jumped to wrong conclusions but since this is the internet, misunderstandings are to be accepted.

As for the topic, since this field is vast (and also that I am just a student), I don't feel confident addressing your questions. So I am going to leave it at that. Good luck with your search for answers though.


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## shontay (Mar 1, 2007)

thanks ag.


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