Butalbital; used with baclofen- pharmacological interactions?

[alkap555]

My primary qualm is that the criterion of profitability often diverges from efficacy of treatment. This occurs mainly because individuals and insurance providers will pay similar sums for modestly effective treatments in a field composed entirely of modestly effective treatments as they would for highly effective treatments in a field composed mostly of highly effective treatments. eg, ask yourself why we have developed 437890254732 SSRIs in the last two decades while the pursuit of alternative avenues has for the most part stagnated.

All of this is certainly true, but for the most part (AFAIK) this problem is unique to psychiatric medications. I think a lot of that has to do with the fact that we simply don't know enough about the pathogenesis/neurobiology of depression, anxiety etc. Because they involve the psyche and conscious perception they are inherently more difficult to investigate and treat than purely physical ailments, IMO. Not only do we lack a "grand unified theory" of depression (to steal some physics lingo), but how do we differentiate between the psychological and neurobiological aspects of any psychiatric disease?

It's not so much that I agree with a purely profit-driven drug development paradigm, but I think that it is a necessary evil. In the end it generates the greatest good for the greatest number of people IMO.

 

[alkap555]

AlphaOdure: Just out of curiosity, how did you manage to get to such a large dose? More importantly, are you under the care of a physician (was it Rxed)?

**Don't answer if you'd rather not discuss it...I am simply curious as to how long it took to achieve your current dose and tolerance.

Let us know how the baclofen/benzo-assisted taper progresses. Good luck.

 

[AlphaOdure]

....
It's not so much that I agree with a purely profit-driven drug development paradigm, but I think that it is a necessary evil. In the end it generates the greatest good for the greatest number of people IMO.

I could not more thoroughly disagree. While profit driven pharmaceutical development is a necessary evil, it can be mediated into areas where it is needed. If it is "the greatest good for the greatest number of people".. why then are millions of individuals dying in Africa & the Middle East due to inability to afford the pricey drugs that will save their lives? While fucking erectile dysfunction medications are the most commonly & highest sold elective medicines in the west. Suuure, this system is definitely "generating the greatest good for the greatest number of people." I suppose it depends on your definition of "good."

No, I believe Africans & Middle-Eastern individuals (along w/ AMERICANS) ought to be able to vote, via their representative, for what direction their pharmaceutical (& medical) industry should traverse to treat common issues of public health (w/ adequate deference to trained individuals of course via a contracting system, of sorts). I advocate a NHS-type system (as an American), or single-payer system--all of which still have room for a profit based systems & elective care. But the stats don't lie. We spend more (and more and more by every year that passes) as a percentage of GDP than any other nation on earth--with the SHITTIEST net result in the west (while 20 million people are ignored for healthcare. Yea, sorry, you can't walk into an ER if you have cancer & get chemotherapy). BUT OH NO.. riight.. our for-profit-system is doing just SWELL. The statistics don't lie.

I don't mean to be a dick, I really don't! But, i'm passionate on this particular civic issue.

 

[AlphaOdure]

AlphaOdure: Just out of curiosity, how did you manage to get to such a large dose? More importantly, are you under the care of a physician (was it Rxed)?

**Don't answer if you'd rather not discuss it...I am simply curious as to how long it took to achieve your current dose and tolerance.

Let us know how the baclofen/benzo-assisted taper progresses. Good luck.

Well, my suboxone doctor refused to treat my GABAergic dependency; so i moved to carisoprodol.. which was very easily available via OP's over the internet up until 2011 (in the US). I had utilized butalbital off and on & was prescribed it off & on by an old family doctor. i saw during this time that butalbital (or the fioricet formula) adequately quelled w/d from carisoprodol.. I quickly moved to this medicine once carisoprodol/soma was scheduled. I immersed myself in the online-pharmacy "scene" to obtain adequate relief, from adequate vendors. Since i'm not privileged enough to be offered health insurance.

So.. as of now, i'm at my typical dose of butalbital. Steady though, at least i'm not increasing 8) ...no baclofen. no benzodiazepines. Although.. given a bonus next week; I am planning on utilizing my IOP connections to test the efficacy of triazolam in affecting my butalbital intake; or possibly meprobamate.

Anyway, back to the topic! OK, its my understanding that there are different "species" of GABA-a receptors, each containing different combinations of GABAergic subunits (alpha, delta, gamma.. i believe thats it?). Benzodiazepines act as positive modulators at a particular "kind" of these GABA-a receptors. Barbiturates have a different binding site at GABA-a receptors, w/ a different particular subunit makeup; so.. in some term they can overlap. Carbamates & older generations are thought most likely to act on barbiturate binding sites; or at least GABA-a receptors similar to the barb-binding site. As far as the phenomena of GABA-b agonists (baclofen) seemingly blocking the efficacy of barbiturates i experienced? Who knows... the GABA system is incredibly complex; & PHRMA (correct spelling, for those who KEEP MISSPELLING IT. It's an acronym for a LOBBYING organization, its not an abbreviation) & its allies have merely peddled these medications w/o any concern for their pharmacology (the one draw back of ONLY using double-blind studies for FDA approval & drug development; the whole privatized system just STINKS).

 

[MeDieViL]

This is purely anecdotel dont just try this however according to a friend you can abrubtly switch from benzo's to barbs for 2 weeks then stop the barb and your withdrawn of the benzo, PERHAPS (wich can be doubtfull as barbs are more potent) you can do it the other way too. Either way my point is that it doesnt seem that they are cross dependent and that a benzo may be helpfull in any tapers.

 

[AlphaOdure]

So this thread has taught me a good bit about relevant details of GABAnergic agonism. I have two main questions:

1. How wide is the gulf between GABA-A and GABA-B mediated inhibition? To the extent that the relevant processing pathways are entirely separate or profoundly downstream, we should expect concurrent GABA-A and GABA-B agonism (or positive allosteric modulation thereof, as is usually the case with GABA-A 'agonism') to be additive in effect. But to what extent is it synergistic? How do we account for such synergy?

2. To what extent is neural adaptation to exogenous GABAnergic agonists specific to these ligands' effects? That is, to what extent will there be cross-tolerance between GABA-A and GABA-B agonists? To the extent that tolerance is limited to receptor downregulation, I would expect tolerance to be highly specific. But to what extent are other mechanisms, eg downregulation of the endogenous conversion of glutamate to GABA, involved?

To partially answer your questions, first- there is a huge gulf between GABA-a & GABA-b exogenous-positive-modulators & agonists, respectively. GABA-b is a metabotropic receptor complex for the endogenously occurring GABA NT'ers. GABA-b is also linked to G-proteins via potassium channels. Second, GABA-a is a alternatively an ionotropic receptor, along w/ being a ligand-gated ion channel, not a G protein receptor. (the GABAergic system is ABSOLUTELY THE MOST INTRICATE receptor-complex). Both GABA-a & GABA-b receptors & their related subunits have endogenous GABA as their ligands of course.

As far as GABA-a/GABA-b positive allosteric modulators/agonists impacting decarboxylation of glutamate to GABA, I don't think this occurs to any major effect--or at least, i haven't read anything on this. I am sure a small amount of this does occur--but most downregulation is specific to each ligand's respective receptor subunit AFAIK. There is certainly synergetic effects between both GABA-a & GABA-b ligands, i suspect however this occurs via a deeper mechanism rather than through GABAergic cross tolerance.. B/c there is no cross tolerance between GABA-a positive allosteric modulators & GABA-b agonists. This can be obviously seen, in that, withdrawal from even moderate dependencies on potent & short acting GABA-b agonists like GHB do not respond with even extremely high doses of benzodiazepines (however, barbiturates.. which are GABA-a PAM's but do not bind at the GABA-a benzodiazepine sites--at the GABA-a beta binding sites I believe--),

While GABA-a PAM's aren't terribly effective in replacing GABA-b dependencies... early research is showing that GABA-b agonists (particularly baclofen, a very purely acting GABA-b agonist) are more effective in replacing GABA-a PAM's; especially ethanol--albeit these results are preliminary and MAY be reversed in future university research, if some attempt to do so; b/c there's absolutely ZERO interest by big PhRMA here in the US for GABA-b meds!

Hope this helps.