Is baclofen a gabapentinoid?

[aspiringchemist]

I cannot seem to find any information directly stating that baclofen is a gabapentinoid. However, phenibut is listed consistently as within this class and is near identical to baclofen.

I do remember reading somewhere (no reference...) that because baclofen is so much more potent by weight that not enough is able to be ingested to achieve this action, unlike phenibut. So that would imply that baclofen is a gabapentinoid but toxicity is reached before this effect occurs?

Thoughts on reduction in dose and combing the two for musculoskeletal pain and spasms to get the best of both compounds?

For clarification, I'm referring to therapeutic use due to chronic pain and spasms. I am currently prescribed baclofen 10mg 4 times daily and diazepam 5mg twice daily.

sorry for the crappy post, I'm hurtin' today

thanks!

 

[Scrofula]

No. Baclofen is a muscle relaxant that has effects on the GABA B receptor class, found in muscle; gabapentin binds at alpha2/delta subunits of (I think just) GABA-A complexes in the CNS. So both different parts of the body and different parts of the receptor (but I'd bet the Baclofen has some CNS activity since folks claim to get loopy with it).

Ok, I checked phenibut and it is "recently discovered" to have affinity for the gabapentin binding site, so maybe baclofen will be discovered to bind there too.

If baclofen does bind with some strength to alpha2delta, I doubt it'd be a source of any toxicity--more like the dose would be so high to get an effect there, you'd go limp and stop breathing first, all from GABA B effects.

Anyway, obv. not an MD, but gabapentin, plus muscle relaxers, plus a benzo, even though they all mainly target different sites, seems like a lot of potential CNS depression.

(Also, good luck--my pain went away on its own, and I get to use my gabapentin for purely recreational purposes)

[EDIT: NO GABAPENTIN DOES NOT BIND TO GABA-A RECEPTORS I AM AN IDIOT DISREGARD]

 

[Solipsis]

I'd be careful with phenibut in this scenario because it's known to cause increased sensitivity to pain / soreness (not sure if actual allodynia), these days that effect is bad enough to keep me from taking it.

Probably the 'confusion' is that phenibut is both a gabapentinoid (acting on VDCCs) as well as a GABA B agonist. It is still a matter of debate how significant exactly those effects occur compared to each other but it seems that phenibut is a lesser GABA B agonist and mostly becomes a significant one at high doses.

So phenibut has overlap of these effects.
But baclofen is the opposite: it is mainly a GABA B agonist like scrofula said, but a lesser VDCC modulator - some 5 times less than phenibut in terms of affinity.

It's questionable whether you reach 'toxicity' before you get the 'minor' side of the effects of each of these drugs, but it seems like a bad idea and highly inefficient if that would be the reason for increasing dosage.

I think it's best to just stick to the baclofen for you given its muscle relaxing action. Gabapentinoids don't really seem to help with that as far as I know and if you're wondering about the general painkilling potential, pregabalin or gabapentin could be interesting out of the gabapentinoids since those don't have the profile of phenibut of possibly/often potentiating pain and soreness, nor any stacking effect on GABA B, which although minor isn't ideal if you are already taking baclofen.
Seems hard to say in which cases you would really expect synergy between say baclofen and gabapentin since at the same time application may be specific like nerve pain but at the same time work for "vague" syndromes like fibromyalgia. But you probably wouldn't be walking in any straight line even if the pain would be gone.

 

[aspiringchemist]

If baclofen does bind with some strength to alpha2delta, I doubt it'd be a source of any toxicity--more like the dose would be so high to get an effect there, you'd go limp and stop breathing first, all from GABA B effects.

Anyway, obv. not an MD, but gabapentin, plus muscle relaxers, plus a benzo, even though they all mainly target different sites, seems like a lot of potential CNS depression.

I don't take gabapentin. I have tried it therapeutically and it did nothing but make me tired and loopy.

I take baclofen and diazepam. The question is in regard to lowering the baclofen dose and supplementing with phenibut, not full doses of each.

Regarding baclofen's questionable gabapentinoid action, this is what I meant, just wasn't articulating it correctly. Essentially, baclofen could have this effect but you would have to take too much and intoxication would occur first.

I was not aware of phenibut causing an increase in sensitivity to pain.

for clarification, I was not referring to high doses of all drugs. What I meant was, IF phenibut was a gabapentinoid with less gaba b action and baclofen a gaba b agonist with less gabapentinoid action, would taking a lower dose of each give you the gaba B effects plus action on VDCC's.
What I'm gathering is that the doses needed for these effects would be too high.

I'm aware it's a lot of gaba drugs. in an area where pain management no longer includes opioids, this is what I have to work with.

thanks for the clarification!

 

[Scrofula]

Well, my main answer was to your big thread question, "Is baclofen a 'gabapentenoid'", which until yesterday I admit I thought was a . . . sign you were in pain.

I think I get your reasoning, and I also just realized I bet baclofen does NOT have much affinity for [alpha2delta, voltage-gated calcium channel subunit of GABA receptor class A, gabapentin binding site] or the manufacturer would have already re-patented is as BacloGaba: Relieves All Suffering. Lyrica makes billions--you know they all immediately ordered some VDCC assay. And don't forget, before it became Neurontin, gabapentin was just a GABA analog, expected to bind where GABA does.

But so your thoughts WERE to add (or at least increase) an extra tine in your GABAfork: GABA B, GABA A benzo, and GABA A VDCC. (An aside, those VDCC-containing receptors are found not just in different brain regions, but different parts of the cell body, to benzo sites, so you'd be touching nearly all your brain too). I bet 2 out of 3 means a letter from DMV.

Anyway, sorry again about the suffering. I wish I could suggest a whole new branch of receptor systems to explore.

[EDIT: NO GABAPENTIN DOES NOT BIND TO GABA-A RECEPTORS I AM AN IDIOT DISREGARD]

 

[sekio]

Phenibut lacks the activity profile of gabapentin/pregabalin. It's a GABA-B agonist, not a calcium-channel modulator/GAT/BCAT modulator.

 

[Scrofula]

@sekio: Wikipedia points to Zvejniece et al., Pharmacology Biochemistry and Behavior. 137: 23–29, as saying phenibut does indeed have affinity for the subunit in question.

I just took their word, no longer at an inst. with a license to read it anyway, didn't see any Km.
OP wondered if same might be true for baclofen, and at what possible strength.

 

[Solipsis]

"R-phenibut binds to the α2-δ subunit of voltage-dependent calcium channels and exerts gabapentin-like anti-nociceptive effects."

https://www.ncbi.nlm.nih.gov/pubmed/26234470

I think the question is more whether the GABA B agonism is minor or not, but the VDCC activity does not appear to be negligible but rather major or at least comparable. I found data a bit lacking on comparing efficacies but that could just be my noobness.

I have no idea though what causes the increased sensitivity to pain, even if it's an unusual side-effect (for me it is not that unusual, I also hear dudes like Xorkoth getting it but not being put off by it as much as I am, clearly)...
For that matter I don't know what makes GHB [able to] cause this effect either, it's not unthinkable it's the same sort of mechanism.

By the way, I don't really think the big issue is necessarily that these drugs get toxic before you would ever get anything out of combining them, but the increased pain sensitivity - if you get it - seems quite counterproductive in a case like yours. If you were to combine with pregabalin/gabapentin instead of phenibut it might not be so bad, although I'm not encouraging any of that either.
The antinoniceptive effects of gabapentinoids are mainly neuropathy-related and hardly generally numbing like say opioids, I think this would explain the apparent paradox of phenibut being able to amplify or cause pain and also relieve it. Although I admit it is still confusing.

 

[Cotcha Yankinov]

I've never used phenibut personally but I wouldn't be surprised if there could be kindling and rebound neuropathic pain. Both the alpha2delta antagonists and GABA-B agonists can decrease pre-synaptic release of neurotransmitters like glutamate that can be involved in neuropathic pain, and there could be a compensatory upregulation for this that we begin to eat as the drug leaves our CNS.

Some people certainly get severe gabapentin/lyrics withdrawals. There could also be some aspect of stress on the withdrawal inducing some sensitization.

But just to clarify, baclofen can function beneficially for neuropathy and neurotoxicity of a manner because GABA-B agonism can decrease the pre-synaptic release of neurotransmitters, its muscle relaxant effects aside.

 

[Solipsis]

If that is true it would be not withdrawal but paradoxical effects we're talking about. I don't get these effects afterwards but during (for both GHB and phenibut, though no other withdrawals at all are noticed during or after), while for pregabalin / gabapentin I don't even get this particular sort of sore fucking feeling upon discontinuation, and I am familiar with pains from pregabalin withdrawals which are quite different.

I would [almost?] try phenibut again one of the following days to get some fresh experience to report on, however my ongoing pregabalin script kind of screws with the cleanliness of the experiment. And you know what they say... Mr Clean is next to Mr God.

By the way thanks for all the info in that daily LSD for ADHD thread, that was awesome, cotcha

 

[Cotcha Yankinov]

Oh it's actually during use? Hmmmmmmm...

The other thing is that SNRIs are thought to work for neuropathic pain by boosting the efferents that travel from the brain down to inhibit pain transmission in the spinal cord dorsal root ganglia, so maybe there is potential for the opposite effect?

We would think that phenibut would decrease pain sensitivity if only acting in the periphery but I guess one explanation is that it's doing something odd to the sensory cortex or brainstem.

And of course, thank you

 

[aspiringchemist]

Well, my main answer was to your big thread question, "Is baclofen a 'gabapentenoid'", which until yesterday I admit I thought was a . . . sign you were in pain.

I think I get your reasoning, and I also just realized I bet baclofen does NOT have much affinity for [alpha2delta, voltage-gated calcium channel subunit of GABA receptor class A, gabapentin binding site] or the manufacturer would have already re-patented is as BacloGaba: Relieves All Suffering. Lyrica makes billions--you know they all immediately ordered some VDCC assay. And don't forget, before it became Neurontin, gabapentin was just a GABA analog, expected to bind where GABA does.

But so your thoughts WERE to add (or at least increase) an extra tine in your GABAfork: GABA B, GABA A benzo, and GABA A VDCC. (An aside, those VDCC-containing receptors are found not just in different brain regions, but different parts of the cell body, to benzo sites, so you'd be touching nearly all your brain too). I bet 2 out of 3 means a letter from DMV.

Anyway, sorry again about the suffering. I wish I could suggest a whole new branch of receptor systems to explore.

Yes, this is what I am getting at.
what do you mean 2 out of 3 means a letter from DMV?

 

[aspiringchemist]

The antinoniceptive effects of gabapentinoids are mainly neuropathy-related and hardly generally numbing like say opioids, I think this would explain the apparent paradox of phenibut being able to amplify or cause pain and also relieve it. Although I admit it is still confusing.

This makes a lot of sense.
I played too hard with phenibut some months ago for about 2 weeks, daily dosing of 2grams. I've kicked IV dope numerous times and this pheni withdrawal was awful.
Actually last time I was at the doctor I was also on methocarbamol 750mg three daily with baclofen and diazepam. I again asked to be put back on narcotic medications in lieu of some gaba drugs because my pain is "mechanical" they say. They literally tell me neuropathic medications will not help my condition and then continue trying to preacribe them to me. I have no neuropathic pain, yet they just want to load me up with gaba drugs. The doc tried to give me pregablin after I outlined the amount of gaba drugs and general sedatives and the lack of effective pain management.
Gabapentin at a high dose with proper titration did nothing for my pain. I am finding the combination of diazepam and baclofen to work fairly well, but it still is lacking at times.
I just walked out.

so why am I asking about phenibut? I have no idea, desperation I guess.

Thanks everyone for the incredibly thoughtful conversation

 

[Scrofula]

Yes, this is what I am getting at.
what do you mean 2 out of 3 means a letter from DMV?

Being snarky. What I'm saying is that you were thinking of adding a drug that targets the same depressive system, in an additive way. Like, "just two beers, officer. And a bunch of Valium." And then, "Oh, and muscle relaxers."

Knowing nothing, it just sounds bad to me, but I don't know the kinds of pain your having, thankfully.

I played too hard with phenibut some months ago for about 2 weeks, daily dosing of 2grams. I've kicked IV dope numerous times and this pheni withdrawal was awful.

I kind of suspected something like that. As a drunk, I DO know about withdrawal from a GABA agonist. That kind of anxiety is a reason to avoid long-term benzos (I pretend my gabapentin script is different; but I do go off for at least a week every month).

I hollered a bunch in different threads about my suspicions that docs are now prescribing more gabapentinoids than the old benzos to patients they find "problematic". For pain, unless it's a weird thing like those foot tingles I get at night, I don't think either does more than make you care a little less.

So good luck, and I don't know, maybe just lots of weed?

[EDIT: NO GABAPENTIN DOES NOT BIND TO GABA-A RECEPTORS I AM AN IDIOT DISREGARD]

 

[aspiringchemist]

lol ok I was like wait a minute...
I've been on the two for years now daily. The relatively low dose and dependence from daily use don't lead to much cognitive effect; definitely some, but not much without potentiation or other substances.
I fear the day someone decides they think that I should not be on this medication. It has truly changed my life for the better. The dose has remained relatively stable and continues to produce positive results.
I believe physiological dependence for medicinal purpose is not always a bad thing.

Yes, I agree. gabapentinoids seem to be the go to meds right now for the "problematic" patient. Though there is definitely something there, it's not the end all.

Diazepam and baclofen both have some pretty strong anti spasticity and anti spasm effects, so they provide more than cognitive relief IMO.

 

[Scrofula]

I fear the day someone decides they think that I should not be on this medication. It has truly changed my life for the better. The dose has remained relatively stable and continues to produce positive results.
I believe physiological dependence for medicinal purpose is not always a bad thing.

Must say, this site is weird with it's notifications, some go to spam, despite being subscribed, despite adding to contacts, pop up in weird places.

Anyway, just rolled by over a week late to say, yeah, don't let me of all people scold you about the meds you take. I mean, a whole Rx and everything? That's like bible writing, thou shalt take!

Only catch with stuff like benzos is that day you get stuck without them. That panic a lot worse than the reality. And I've always had a bit of a phobia about detention. That's why I make sure I stay addicted to nicotine, clever guy that I am. Nice short half-life, so even movies feel like detention!

[EDIT: NO GABAPENTIN DOES NOT BIND TO GABA-A RECEPTORS I AM AN IDIOT DISREGARD]

 

[Scrofula]

[EDIT: NO GABAPENTIN DOES NOT BIND TO GABA-A RECEPTORS I AM AN IDIOT DISREGARD]

No really, I should have known better.