How does baclofen work? Otter? Tk?

[Otter]

How does baclofen work? Otter? Tk?

terryk;1457948 wrote: Are you trying to poison me?

CGP7930: a positive allosteric modulator of the GABAB receptor [CNS Drug Rev. 2007] - PubMed - NCBI



Adams CL, Lawrence AJ. Department of Pharmaceutical Biology, Victorian College of Pharmacy, Monash University, Australia.

Abstract CGP7930 (3-(3',5'-Di-tert-butyl-4'-hydroxy)phenyl-2,2-dimethylpropanol) is a positive allosteric modulator of the metabotropic GABAB receptor. CGP7930 has been found to modulate the GABAB receptor in the open, or high affinity, state increasing agonist affinity for the receptor and signal transduction efficacy following agonist stimulation. The GABAB heteromeric subunit B2, involved in signal transduction but not ligand binding, seems to be the site of action of CGP7930 and similar allosteric modulators. When administered alone in na?ve animals, CGP7930 acts as an anxiolytic in rodents without other overt behavioral effects and has also been demonstrated to reduce self-administration of nicotine, cocaine, or alcohol in rodents, suggesting that "fine tuning" of the GABAB receptor by positive allosteric modulators may be able to regulate abuse of these drugs. Baclofen, the GABAB agonist, is currently finding use in treating addiction and various other disorders, but this can result in off-target effects and tolerance. CGP7930 when co-administered with baclofen enhances its potency, which could in theory minimize deleterious effects. Further study of CGP7930 is required, but this compound, and others like it, holds potential in a clinical setting.


MID: 17894647 [PubMed - indexed for MEDLINE]

-tk

The article you posted doesn't support what you say. Lots of drugs "affect" the gaga b receptor but they don't "mimic" the effects of GHB. Obviously, the bulking agents in baclofen pills don't "mimic" GHB either which is why liquid baclofen works better and baclofen is not a perfect mimic which is why Seaside and Roache are now developing Arbaclofen which has the left side of the molecule removed.

I just don't see the point of nit picking so, in answer to your question, yes.

[Otter]

How does baclofen work? Otter? Tk?

That was a joke by the way.

[terryk]

How does baclofen work? Otter? Tk?

Otter;1457956 wrote: The article you posted doesn't support what you say. Lots of drugs "affect" the gaga b receptor but they don't "mimic" the effects of GHB. Obviously, the bulking agents in baclofen pills don't "mimic" GHB either which is why liquid baclofen works better and baclofen is not a perfect mimic which is why Seaside and Roache are now developing Arbaclofen which has the left side of the molecule removed.

I just don't see the point of nit picking so, in answer to your question, yes.

From the article's abstract:

"At behaviorally relevant dosages, baclofen activated GIRK channels in both cell types, but the drug of abuse gamma-hydroxy-butyric acid (GHB) activated GIRK channels only in GABAergic neurons."

Baclofen acts differently than GHB.



-tk

p.s. Maybe I'm nitpicking, but accurate information is important....And I'm just not sure that the verdict is in about how baclofen really works.

Excellent reading (free full text):

Unravelling the brain targets of gamma-hydroxybutyric acid

The role of gamma-hydroxybutyric acid in the treatment of alcoholism: from animal to clinical studies.[Alcohol Alcohol. 1999 Jan-Feb] - PubMed - NCBI

[MaryGoRound]

How does baclofen work? Otter? Tk?

I love all that I hear but I am still confused . If I understood what an GABAb agonist is I would not have to ask the questions. Here goes;

1. Is the problem with an alcoholic with concurrent anxiety that there is not enough GABA or not enough (or efficient) receptors?

2. Does Bac simulate GABA chemicals that can be received by the GABAb receptors or does it stimulate growth of GABAb receptors?

I hear the explanations about other parts of the brain that Bac may effect. Dr. L is big on the effect Bac has on the cerebellum. The effect on the amygdala is very interesting but I first want to understand its primary function on GABA.

In my Bac experience, I do notice diminishing rewards of alcohol (eg. euphoria) while increasing potential negatives (eg.bad hangovers) but that is not its main effect on me. After all, I can sometimes drink and still get the pleasant effects without the negative effects. The real deterrent is diminishing thoughts that a drink might be a good idea.

[Cassander]

How does baclofen work? Otter? Tk?

bump

terryk linked to this thread earlier today. Thanks, tk!

I just re-read it from start to end. Very interesting! If I do say so, some of the answers beg additional questions...

Well worth reading.

Cassander

[spiritwolf333]

How does baclofen work? Otter? Tk?

Right on Cass -and this does bring up more questions. This may have been one of the threads I read before my thirty day extended-introduction-to-baclofen vacation. (Vacation my arse). I know that I understood it less then than now. However, when I read it then, I became more convinced that baclofen was a real solution (with all the high end scientific brain terms being used -I just did not think they were making things up for the fun of it)

[Jazi's Mum]

How does baclofen work? Otter? Tk?

Thanks for this information, even if it may be difficult to understand fully (for me that is). Just to know baclofen HAS been studied, and for YEARS, gives me some confidence - to say nothing of all the lab rats here sharing their experiences. Starting my bac attack tomorrow, so thanks!

[Mom21961]

Very interesting information. Thanks tk, for referencing your post on this thread. Bump!

[neophyte]

this is also useful

[Ne/Neva Eva]

Hey, Neo. I found the page in a book that doesn't seem to be available.

(https://books.google.com/books?id=NI...clofen&f=false)

Do you know anything about it? Am I looking in the wrong place? Or did you find it somewhere else? The other things that came up were the De Beaurepaire study and something authored by Felice Nava, about whom I don't know anything.

Info would be appreciated.

[neophyte]

hi Neva, i dont remember where i found that page, it was a while back, probably on here or on reddit. I believe in this video they confirm basically the same mechanism of baclofen but go into much greater detail which is explained by a neuroscientist, its pretty heavy stuff

http://www.radiolab.org/story/addiction/

[Ne/Neva Eva]

Thanks, Neo. Appreciate the response.

I heard that podcast. Was kind of disappointed about it, actually.

I'll keep searching, because it is definitely interesting information. I wonder if there is more.

But I've got plenty on my plate at the moment and don't need to go down Alice's hole...

[Otter]

Ameisen explains it in his book.

I was contacted a while ago by someone who had been taking baclofen under the care of Dr. Chick, who was his prescribing doctor. He also sought advice from Olivier Ameisen and from Phil Thomas. After all that advice from the top people in baclofen he still continued to drink, and, he had a Master's degree in chemistry so he was totally switched on to the science of it.

Anyway, I agreed to give him some counselling and we discussed the theory of baclofen and he said he couldn't figure out how a Gaba b agonist could have an effect on the Gaba A receptors, which is where most mood drugs have their effect. Because of this, he made a rational decision that baclofen could not work as Ameisen said and he lost interest in it and relapsed badly.

I explained to him that he had plainly not read Ameisen's book properly because what Ameisen says, which is significant in alcohol treatment, is that researchers have overlooked the Gaba B receptors as having any involvement in the type of anxiety which actually underlies alcoholism and that is what sets baclofen apart from all other drugs. GHB, a chemical occuring naturally in the brain, calms the brain by acting on the Gaba B receptor. Alcohol mimics GHB. That is why GHB as a synthetic drug is not noticed when used as a date rape drug, because its effects are indistinguishable from alcohol. The two are interchangeable, but obviously alcohol makes you drunk while GHB just calms anxiety.

So, because baclofen is an analogue (the same thing) as GHB, if you take it you won't feel like taking alcohol. I used an analogy of an empty glass. Imagine your Gaba B receptor is just like an empty glass in you head. If you fill it with GHB, you can't then add any alcohol, because there is no more room in the glass. So, you don't crave alcohol. If you are short of GHB, you can then fill the glass with baclofen, and by filling it up, you can't then put any alcohol in the glass.

After I used this analogy and explained Ameisen's theory the person I was advising had a "eureka" moment. None of the people who had advised him explained it in this way. He agreed with the analogy and got back on baclofen. After a few more chats he said he was fine and has been fine ever since, which is nearly a year now. He went back to a high stress job and writes to me now and then to thank me for helping him and all I really did was to give him the glass analogy.

I try not to get to deep into the chemical analysis of the brain. Baclofen acts on dopamine... I prefer the simple analogy of filling the glass because that is what an agonist is, it acts in the same way as the missing brain chemical while Naltrexone is an antagonist so you can't use the same analogy. With baclofen you are not substituting alcohol with another drug which acts in the same way, ie., to give you a Gaba A euphoria. You are replacing missing GHB. Chick is incorrect in saying baclofen is replacement therapy. It isn't. Naltrexon, subudone, methodone and all the drugs which give you a high similar to the drug of choice are replacements for the drug. Baclofen is a treatment of a chemical deficiency and it supplements the organic, natural chemical which your brain misses and it does not give you a Gaba A high.

[Spiritfree]

Otter, the above statements are incorrect.

There is one type of GABA - GABA, the endogenous neurotransmitter. There are chemical analogues of GABA, and also chemicals that act at allosteric modulators (at GABA receptors).

There are GABA receptors, of which there are 2 main types (GABAa and GABAb) and several subtypes.

Baclofen is a GABAb agonist, which means that it acts like GABA does at GABAb receptors. It is surmised that it's unique chemical structure enables it to penetrate the Blood-Brain Barrier and exert a great effect than plain old GABA (which generally can't cross the BBB)

Phenibut is also a drug that acts like GABA at GABAb receptors

Lesogaberan is also a drug that acts GABA at GABAb receptors

GHB (+GBL, 1,4 But, GHV ) is also a drug that acts GABA at GABAb receptors

I've articulated my reasoning that I don't think baclofen works by replacing endogenous GHB. This article is a good read (GHB doesn't modulate dopamine neurons like baclofen does): Bi-directional effects of GABA: B: receptor agonists on the mesolimbic dopamine system : Article : Nature Neuroscience

I've noticed that you base (some of) your info on Phill Thomas' B4a handbook. It contains some of the same errors I've pointed out here.

-tk

What the heck is going on? We are just trying to find out what we can take to make us feel ok without the use of alcohol. Whatever GABA thing you two are talking about really does not matter.

[kronkcarr]

What the heck is going on? We are just trying to find out what we can take to make us feel ok without the use of alcohol. Whatever GABA thing you two are talking about really does not matter.

It mattered to me because I wanted to know what affect baclofen had on my brain. I preferred to know what was physically going on with me. Apparently the gentleman also wanted to know.