Gabapentinoids What Are The Differences Between Gabapentin/Pragabalin and Phenibut

[brokedownpalace10]

What are the differences in mechanism of action between Gabapentin/Pregabalin and Phenibut? I've read on here that Phenibut works the same way as the Gabapentinoids, but that it also has some other, added, things it does in your brain.

I read this within a post not dedicated to this question, so I've finding it hard to search for.

The local CBD store is selling Phenibut now and the employees are talking a lot about it. I'm mentioning how addicting it is, and they seem to be aware of that.
One of my strategies for taking Phenibut without getting addicted and also avoiding the risk of the nasty effects higher doses can have is to take 300/600 mg Phenibut and some also lower doses of Gabapentin and Pregabalin.

Last night I took 600 mg Phenibut, 150 mg Pregabalin, and 200 mg Gabapentin. I have a low tolerance to Gabapentinoids and keep it that way.
I felt pretty great with absolutely no bad effects in sight. The Phenibut flavors the rest nicely.

Anyway, before I get on my soapbox about the similarities and the strategies for Phenibut, I want to know my shit. Especially as to how they work in the brain.

 

[JackARoe]

Here I will say this wrong, or sloppy so someone can come and correct me of what little I know.

Gabapentin, Pregabalin and Phenibut are calcium channel (modulated blah blah blah) and have that in common. Phenibut is also a gaba B agonist of (blah blah blah). There is a better explanation but every time I see it the definition is slightly different.

So I think they are the same except phenibut also acts somehow on gaba B receptors.

That is my rough and dirty explanation of what I know. Hoping someone else clarifies better. Did not want the thread to twist in the wind.

I also keep my tolerance to all of these down. Very sporadic and keep the doses light. No more than 300 mgs of pregabalin or 1800 mgs of gabapentin. I had an opportunity to switch to pregabalin by my doctor but chose to remain with the gabapentin prescription. But most others would do the opposite. I also chose to not take daily. To me gabapentin suits me best and works best. Pregabalin is for sure stronger but I get some type of brain zaps like that are unnerving. Oddly enough the one time I combined gabapentin and phenibut I also got an uncomfortable feeling in my head. So I have to keep these light. Phenibut and pregabalin are stronger and need more forethought. I get a more relaxed body effect with gabaentin than any of the other two.

 

[brokedownpalace10]

Exactly what I was looking for. Thanks. If anyone wants to give greater detail that's great and I'd love it, but that was good. It's GABA B agonism which Phenibut adds to the mix.

I like Gabapentin and Pregabalin combined, but I hardly ever do anything more than very mild doses. One Gabapentin and one Pregabalin is a nice prequel to a night drinking. Makes the alcohol feel less toxic. A couple/few of each with no booze is a relaxing night.

I also am very wary of tolerance/addiction to these drugs and keep use occasional.
I have a chronic pain thing and docs kept throwing them at me when i was working and had better drug coverage. As a machinist, I hated taking them. Needed to be sharp. "Got high" on being sharp. I always filled all the scripts and squirreled them away.

Now I'm retired, so less clarity required but shitty drug coverage. Nibbling away at what I have.

As said, I had a mild dose of all three a couple nights ago. 600mg Phenibut, 200mg Gabapentin, and 150mg Pregabalin. Waited two hours after the Phenibut for the rest. Wasn't overwhelming of course, but was quite pleasant. Next day was too.

 

[Vesicle]

Gabapentin is the prototypical 'gabapentinoid', hence the name. Gabapentin, pregabalin, and phenibut have unique pharmacologies which overlap. They all act as ligands, specifically as 'blockers', of voltage-gated calcium ion channels (VGCC). This is done specifically at the α2δ sub-unit, the significance of this sub-unit is still under investigation.

VGCCs play an important role in your nervous system; when nerve cells are depolarized (i.e. excited), these channels are opened and allow calcium ions to flow into the nerve cell so that the 'wave of excitation' can flow down the axon of the neuronal cell. By 'blocking' these channels, gabapentinoids inhibit neuronal signals. In a broad sense, this is one of the main reasons gabapentinoids are medications used for nerve pain and epilepsy.

It is also worth noting that gabapentinoids may affect glutamate levels by affecting both the release and reuptake of glutamate. The inhibition of VGCCs inhibits vesicular release. Vesicles contain neurotransmitters such as glutamate and must be released to propagate signals to neighboring neurons. A study has also shown pregabalin to improve the responses of glutamate transporters. The significance of these effects are still debated.

The unique effects of gabapentinoids may also be due to the location of their receptors. The α2δ sub-unit is primarily expressed in the brain, especially the cerebellum, as well as the muscle cells of the peripheral nervous system.


https://www.sciencedirect.com/science/article/pii/S0005273612004105

Neuronal α2δ proteins and brain disorders - PubMed

α₂δ proteins are membrane-anchored extracellular glycoproteins which are abundantly expressed in the brain and the peripheral nervous system. They serve as regulatory subunits of voltage-gated calcium channels and, particularly in nerve cells, regulate presynaptic and postsynaptic...

pubmed.ncbi.nlm.nih.gov

Dual effects of gabapentin and pregabalin on glutamate release at rat entorhinal synapses in vitro - PubMed

We have recently shown that the anticonvulsant drugs phenytoin, lamotrigine and sodium valproate all reduce the release of glutamate at synapses in the entorhinal cortex in vitro. In the present investigation we determined whether this property was shared by gabapentin and pregabalin, using...

pubmed.ncbi.nlm.nih.gov

Effects of pregabalin on the activity of glutamate transporter type 3

AbstractBackground. Pregabalin, (S)-3-aminomethyl-5-methyl hexanoic acid, is a ligand for the α2δ subunit (a component of voltage-gated calcium channels) a

academic.oup.com

Pregabalin: Potential for Addiction and a Possible Glutamatergic Mechanism - Scientific Reports

Drug addiction remains a prevalent and fatal disease worldwide that carries significant social and economic impacts. Recent reports suggest illicit pregabalin (Lyrica) use may be increasing among youth, however the addictive potential of pregabalin has not been well established. Drug seeking...

www.nature.com

 

[Vesicle]

Gabapentin is the prototypical 'gabapentinoid', hence the name. Gabapentin, pregabalin, and phenibut have unique pharmacologies which overlap. They all act as ligands, specifically as 'blockers', of voltage-gated calcium ion channels (VGCC). This is done specifically at the α2δ sub-unit, the significance of this sub-unit is still under investigation.

VGCCs play an important role in your nervous system; when nerve cells are depolarized (i.e. excited), these channels are opened and allow calcium ions to flow into the nerve cell so that the 'wave of excitation' can flow down the axon of the neuronal cell. By 'blocking' these channels, gabapentinoids inhibit neuronal signals. In a broad sense, this is one of the main reasons gabapentinoids are medications used for nerve pain and epilepsy.

It is also worth noting that gabapentinoids may affect glutamate levels by affecting both the release and reuptake of glutamate. The inhibition of VGCCs inhibits vesicular release. Vesicles contain neurotransmitters such as glutamate and must be released to propagate signals to neighboring neurons. A study has also shown pregabalin to improve the responses of glutamate transporters. The significance of these effects are still debated.

The unique effects of gabapentinoids may also be due to the location of their receptors. The α2δ sub-unit is primarily expressed in the brain, especially the cerebellum, as well as the muscle cells of the peripheral nervous system.


https://www.sciencedirect.com/science/article/pii/S0005273612004105

Neuronal α2δ proteins and brain disorders - PubMed

α₂δ proteins are membrane-anchored extracellular glycoproteins which are abundantly expressed in the brain and the peripheral nervous system. They serve as regulatory subunits of voltage-gated calcium channels and, particularly in nerve cells, regulate presynaptic and postsynaptic...

pubmed.ncbi.nlm.nih.gov

Dual effects of gabapentin and pregabalin on glutamate release at rat entorhinal synapses in vitro - PubMed

We have recently shown that the anticonvulsant drugs phenytoin, lamotrigine and sodium valproate all reduce the release of glutamate at synapses in the entorhinal cortex in vitro. In the present investigation we determined whether this property was shared by gabapentin and pregabalin, using...

pubmed.ncbi.nlm.nih.gov

Effects of pregabalin on the activity of glutamate transporter type 3

AbstractBackground. Pregabalin, (S)-3-aminomethyl-5-methyl hexanoic acid, is a ligand for the α2δ subunit (a component of voltage-gated calcium channels) a

academic.oup.com

Pregabalin: Potential for Addiction and a Possible Glutamatergic Mechanism - Scientific Reports

Drug addiction remains a prevalent and fatal disease worldwide that carries significant social and economic impacts. Recent reports suggest illicit pregabalin (Lyrica) use may be increasing among youth, however the addictive potential of pregabalin has not been well established. Drug seeking...

www.nature.com

Just found this image; might help illustrate my point better.

 

[brokedownpalace10]

That one was actually pretty easy to picture.

Just found this image; might help illustrate my point better.

It was the

It is also worth noting that gabapentinoids may affect glutamate levels by affecting both the release and reuptake of glutamate. The inhibition of VGCCs inhibits vesicular release. Vesicles contain neurotransmitters such as glutamate and must be released to propagate signals to neighboring neurons. A study has also shown pregabalin to improve the responses of glutamate transporters. The significance of these effects are still debated.

which was harder without research I was too lazy to do. The Gabapentinoids are glutamate agonists/reuptake inhibitors?

 

[Vesicle]

That one was actually pretty easy to picture.

It was the

It is also worth noting that gabapentinoids may affect glutamate levels by affecting both the release and reuptake of glutamate. The inhibition of VGCCs inhibits vesicular release. Vesicles contain neurotransmitters such as glutamate and must be released to propagate signals to neighboring neurons. A study has also shown pregabalin to improve the responses of glutamate transporters. The significance of these effects are still debated.

which was harder without research I was too lazy to do. The Gabapentinoids are glutamate agonists/reuptake inhibitors?

They are neither agonists nor reputake inhibitors, they indirectly affect glutamate levels. This is what either from inhibiting vesicular release , or promoting the activity of glutamate transporters . I wouldn’t call them glutamate agonists/antagonists, but i would call them glutamatergic due to their indirect but somewhat significant ability to affect glutamate levels.

 

[brokedownpalace10]

They are neither agonists nor reputake inhibitors, they indirectly affect glutamate levels. This is what either from inhibiting vesicular release , or promoting the activity of glutamate transporters . I wouldn’t call them glutamate agonists/antagonists, but i would call them glutamatergic due to their indirect but somewhat significant ability to affect glutamate levels.

OK. So, I'm in in over my head, but here goes. Gabapentinoids for dummies.

Glutamate is an excitatory neurotransmitter critical in learning and cognition.(?)
The calcium channel blocking effect damps down nerve impulses, including in the brain.
Wow.
So, maybe that's why gabapentinoids give you a kinda clear headed relaxation? Would also explain why coming off them sucks.

 

[Vesicle]

OK. So, I'm in in over my head, but here goes. Gabapentinoids for dummies.

Glutamate is an excitatory neurotransmitter critical in learning and cognition.(?)
The calcium channel blocking effect damps down nerve impulses, including in the brain.
Wow.
So, maybe that's why gabapentinoids give you a kinda clear headed relaxation? Would also explain why coming off them sucks.

Nice summation! It's also worth mentioning that glutamate plays a role in many bodily functions. While it is important in learning and cognition, it is also the most abundant excitatory neurotransmitter in the body. It is also interesting to note that glutamate acts as a precursor to GABA, the main inhibitory neurotransmitter in the body that we typically associate with anxiolytic medications.

Pregabalin does not affect GABA but as we have discussed, it may play a role in inhibiting glutamate expression through various means. GABA is primarily made from glutamate via an enzyme called glutamate decarboxylase.

So perhaps inhibition of glutamate results in a significant change in GABA levels? This is likely not the case as less glutamate would imply less GABA synthesis. It is more likely (just speculating here) that the decreased glutamate activity makes the balance/ratio between glutamate and GABA imbalanced, with GABA activity remaining constant and glutamate activity decreasing. This would, in theory, result in GABAergic systems being more active than glutamatergic systems (in comparison).

https://www.sciencedirect.com/science/article/pii/S0022316622140290

https://journals.sagepub.com/doi/10.1177/1073858402238515

 

[xtcgrrrl]

So this is why I’m stupider when I take too much gabapentin? Interesting.

 

[BourbonMac]

Yeah people call it "morontin" for a reason, people find it slows them down at higher doses especially longterm.
Phenibut, like gabapentin will have reduced absorption when taken with magnesium, I experienced this last winter. Gabapentin and phenibut do synergize quite well though. I still have lots of phenibut but I'm tapering gabapentin now and kind of fell out of love with it. Amazing substance for awhile, it was like xanax and MDMA when I'd take 1.5-2g but Idk, it was too intense and it takes way too damn long to kick in. I'd get absolutely crazed manic on the stuff.

 

[Fire&Water]

Ones a shitty excuse for a durg
next ones a little less shitty
last ones the shittiest

 

[brokedownpalace10]

Nice summation! It's also worth mentioning that glutamate plays a role in many bodily functions. While it is important in learning and cognition, it is also the most abundant excitatory neurotransmitter in the body. It is also interesting to note that glutamate acts as a precursor to GABA, the main inhibitory neurotransmitter in the body that we typically associate with anxiolytic medications.

Pregabalin does not affect GABA but as we have discussed, it may play a role in inhibiting glutamate expression through various means. GABA is primarily made from glutamate via an enzyme called glutamate decarboxylase.

So perhaps inhibition of glutamate results in a significant change in GABA levels? This is likely not the case as less glutamate would imply less GABA synthesis. It is more likely (just speculating here) that the decreased glutamate activity makes the balance/ratio between glutamate and GABA imbalanced, with GABA activity remaining constant and glutamate activity decreasing. This would, in theory, result in GABAergic systems being more active than glutamatergic systems (in comparison).

https://www.sciencedirect.com/science/article/pii/S0022316622140290

https://journals.sagepub.com/doi/10.1177/1073858402238515

So gabapentinoids suppress glutamate?



BourbonMac, xtcgrrrl, that's exactly why I am not on Gabapentin or Pregabalin even though it's the latest "wonder drug" and docs have basically thrown it at me for years.
I've heard the "morontin" moniker as well and it certainly is true in my case. When you are a CNC machinist running a million dollar machine and your job is essentially to set it up and run it so that it does not crash causing thousands of dollars worth of damage, you want to be kinda sharp.

 

[Vesicle]

So gabapentinoids suppress glutamate?

Yes, there is evidence that gabapentinoids inhibit glutamate activity. The implications of this are still being researched.

 

[Dextro .45]

Gabapentinoids inhibit the release of several excitatory neurotransmitters, including Glutamate, Substance P, Dopamine, Norepinephrine, etc.

I noticed after taking daily Gabapentin the daily oral Methylphenidate (Ritalin) wasn’t as pleasurable as normally. Phenibut was not issue at is has mild to moderate dopaminergic properties in addition to being an anxiolytic, and it has a Phenylethylamine skeletal structure. Pregabalin is very euphoric and pleasurable and I take always in my Brompton Cocktail with opioids, stimulants, benzodiazepine, ethanol, cannabis, etc

Methylphenidate (Ritalin) is a VERY pleasurable dopaminergic stimulant nearly identical to Cocaine. An excellent safety profile, very little increase in HR & BP compared to Amphetamines

Cocaine
Methylphenidate (Ritalin)
Phenmetrazine
Benzedrine
Dexedrine
Methedrine (Desoxyn)
Biphetamine
Dexamyl & Desbutal

The only TRUE dopaminergic stimulants releasing / increasing large amounts of Dopamine / monoamines in the brains reward centre

Dopaminergic stimulant (Ritalin, Dexedrine, Methedrine)
Opioid (Oxycodone, Dilaudid, Heroin)
Benzodiazepine (Xanax & Valium)
Gabapentinoid (Lyrica or Phenibut)
Ethanol (Jin or Rum)

Ultimate oral hybrid Brompton Cocktail I take daily after work as a treat & relaxation therapeutic state in front of my crackling fireplace in the winter, next to patio, and 65” 4K smart tv lol….cleaning one of my toyz while watching a cool documentary

 

[PtahTek]

I say amongst other differences there is weight to consider.
Phenibut one may need grams... like gabapentin. Pregabalin takes the least of the three to "work" for me.