Gabapentinoids Gabapentin & Naloxone....

[DeathIndustrial88]

Antinociceptive effects of gabapentin & its mechanism of action in experimental animal studies

Several studies have shown the possible analgesic effects of gabapentin, widely used as an antiepileptic. Thus, clinical studies have been carried out especially for neuropathic syndroms. This study was undertaken to investigate experimentally whether ...

www.ncbi.nlm.nih.gov

Anyone care to pick this study apart?

It speaks about 2 different experiments and in one experiment, they found that naloxone reversed the analgesic relief of gabapentin, while the other experiment said it didn't.

"Gabapentin (30 mg/kg) combined with naloxone in our experimental study did not reveal any peripheral effect. However, Hansen et al19 observed that gabapentin at spinal level prevents opiod tolerance, and reveals a better spinal analgesic effect compared to single use6, and that the antinociceptive effect of gabapentin is reversed with naloxone16. These studies were conducted with neuropathic pain models."

It also mentions that gabapentin reverses morphine tolerance..

I initially looked up this information because I am prescribed gabapentin and suboxone. I noticed the other day after taking a dose of gabapentin and it being in full effect, I took some more suboxone and what happened next I can only describe as sudden precipitated withdrawal. Sweats, a return of pain (all through out my body), dysphoria, etc...

I have given myself precipitated withdrawal several times in the past from taking subs too soon after heroin. This felt exactly like that, but lasted only maybe about 20 minutes.

If naloxone could reverse gabapentin, wouldn't that imply some sort of opioid mechanism? And which study should be believed since the study in the link says naloxone had no effect on gabapentin.

I have also read that gabapentin has pretty much nothing to do with gaba or the gaba A & B receptors, yet this study says...
"It has been reported that gabapentin slightly increases the systolic and diastolic blood pressure on intra-cerebroventricüler administration5–7. Studies have primarily been conducted on its effects on GABAB receptors4."

So which is it, does gabapentin affect gaba B receptor or does it not?

Any one with a little more understanding about all this care to pick it apart?
Was the precipitated withdrawal I felt all in my head?
And I have noticed hallucinations from gabapentin withdrawal, which to me would indicate some kind of action at one of the gaba receptor sites (I would think).

Any one with any more input or knowledge (in layman's terms) of the mechanism of action of gabapentin?

 

[deficiT]

I really can't speak on the neuroscience as I'm not sure exactly how gabapentin works beyond the fact that it acts on the calcium channels and can effect NMDA levels, amongst other things.

But anecdotally at least, I take Suboxone and gabapentin and have never found myself in a precipitated withdrawal. I mean I usually take my Suboxone before the gabapentin these days, but I used to take the gabapentin first and never ran into it.

Hopefully someone will come by who might be able to better enlighten us.

 

[DeathIndustrial88]

I really can't speak on the neuroscience as I'm not sure exactly how gabapentin works beyond the fact that it acts on the calcium channels and can effect NMDA levels, amongst other things.

But anecdotally at least, I take Suboxone and gabapentin and have never found myself in a precipitated withdrawal. I mean I usually take my Suboxone before the gabapentin these days, but I used to take the gabapentin first and never ran into it.

Hopefully someone will come by who might be able to better enlighten us.

Thanks for the response!

I too read that it affected NMDA. I wonder if that could lower/prevent/reset opioid tolerance as other NMDA drugs can (i.e. - DXM), but I'm not exactly educated enough or understand enough on just how exactly it affects NMDA.

The day this happened, I was feeling alright (pain wise) after having taken my gabapentin and then took some more suboxone later in the day and within 2 minutes was drenched in sweat and had to lay down.

Thought about testing it out and trying it again but I'd prefer not to have to feel that way again.

I also find it weird that one study says gabapentin was reversed by naloxone (which would suggest gabapentin has actions at the opioid receptors) while another study says they didn't see that result. Hard to tell which study is the truth then though....

 

[psynce of sound]

Antinociceptive effects of gabapentin & its mechanism of action in experimental animal studies

Several studies have shown the possible analgesic effects of gabapentin, widely used as an antiepileptic. Thus, clinical studies have been carried out especially for neuropathic syndroms. This study was undertaken to investigate experimentally whether ...

www.ncbi.nlm.nih.gov

Anyone care to pick this study apart?

It speaks about 2 different experiments and in one experiment, they found that naloxone reversed the analgesic relief of gabapentin, while the other experiment said it didn't.

"Gabapentin (30 mg/kg) combined with naloxone in our experimental study did not reveal any peripheral effect. However, Hansen et al19 observed that gabapentin at spinal level prevents opiod tolerance, and reveals a better spinal analgesic effect compared to single use6, and that the antinociceptive effect of gabapentin is reversed with naloxone16. These studies were conducted with neuropathic pain models."

It also mentions that gabapentin reverses morphine tolerance..

I initially looked up this information because I am prescribed gabapentin and suboxone. I noticed the other day after taking a dose of gabapentin and it being in full effect, I took some more suboxone and what happened next I can only describe as sudden precipitated withdrawal. Sweats, a return of pain (all through out my body), dysphoria, etc...

I have given myself precipitated withdrawal several times in the past from taking subs too soon after heroin. This felt exactly like that, but lasted only maybe about 20 minutes.

If naloxone could reverse gabapentin, wouldn't that imply some sort of opioid mechanism? And which study should be believed since the study in the link says naloxone had no effect on gabapentin.

I have also read that gabapentin has pretty much nothing to do with gaba or the gaba A & B receptors, yet this study says...
"It has been reported that gabapentin slightly increases the systolic and diastolic blood pressure on intra-cerebroventricüler administration5–7. Studies have primarily been conducted on its effects on GABAB receptors4."

So which is it, does gabapentin affect gaba B receptor or does it not?

Any one with a little more understanding about all this care to pick it apart?
Was the precipitated withdrawal I felt all in my head?
And I have noticed hallucinations from gabapentin withdrawal, which to me would indicate some kind of action at one of the gaba receptor sites (I would think).

Any one with any more input or knowledge (in layman's terms) of the mechanism of action of gabapentin?

Ca+ channels are pivotal in generation of action potentials in the axon.
So they are pretty ubiquitous and will indirectly affect a lot of things.

Also I'd imagine there is some g protein activity going on if it's effecting Opioid tolerance.

 

[DeathIndustrial88]

Ca+ channels are pivotal in generation of action potentials in the axon.
So they are pretty ubiquitous and will indirectly affect a lot of things.

Also I'd imagine there is some g protein activity going on if it's effecting Opioid tolerance.

Im a little ignorant to some of what you said, but I appreciate the response. Gabapentin seems like an odd drug that they aren't even sure how it works.

 

[psynce of sound]

Im a little ignorant to some of what you said, but I appreciate the response. Gabapentin seems like an odd drug that they aren't even sure how it works.

Would you like me to explain it in more simple terms. My apologies for putting it as I do, it's a bad habit of mine.

 

[DeathIndustrial88]

Would you like me to explain it in more simple terms. My apologies for putting it as I do, it's a bad habit of mine.

Sure, if you have the time, I'd appreciate it! Thank you!

I've been studying pharmacology for a few years (my own research, not school or anything), so I recognize some of the terms you used, just not quite sure I understand them or what's happening when calcium channels are inhibited or what the g protein and opioid tolerance mean.

And no apologies! Glad to have some one here who knows what they're talking about! I appreciate any and all answers!

 

[psynce of sound]

Sure, if you have the time, I'd appreciate it! Thank you!

I've been studying pharmacology for a few years (my own research, not school or anything), so I recognize some of the terms you used, just not quite sure I understand them or what's happening when calcium channels are inhibited or what the g protein and opioid tolerance mean.

And no apologies! Glad to have some one here who knows what they're talking about! I appreciate any and all answers!

Well what happens is the Gabapentoid fits into the pocket in the channel that blocks Calcium ions slotting in there.
This closes the channel and prevents it from then generating as much of a signal in the neurones.
So for example say Morphine is taken alongside it in principle should reduce the level of electrical impulse that would generate.
This is the basic function of how that channel works and Gabapentoids interactions.

As you noted it has further effects here that aren't quantified yet.

My guess about Opioid tolerance is that it may have an effect on a protein found on the surface of cells (the g protein) where a lot of receptors are bound. Opioid tolerance loosely is related to the Mu receptors being taken into the protein and prevented from interacting with anything.
So it's possible it cause something indirectly (i.e. NMDA receptors) that are linked with Mu receptors that causes them to return to the surface.

I hope this is better, let me know if not.

 

[DeathIndustrial88]

Well what happens is the Gabapentoid fits into the pocket in the channel that blocks Calcium ions slotting in there.
This closes the channel and prevents it from then generating as much of a signal in the neurones.
So for example say Morphine is taken alongside it in principle should reduce the level of electrical impulse that would generate.
This is the basic function of how that channel works and Gabapentoids interactions.

As you noted it has further effects here that aren't quantified yet.

My guess about Opioid tolerance is that it may have an effect on a protein found on the surface of cells (the g protein) where a lot of receptors are bound. Opioid tolerance loosely is related to the Mu receptors being taken into the protein and prevented from interacting with anything.
So it's possible it cause something indirectly (i.e. NMDA receptors) that are linked with Mu receptors that causes them to return to the surface.

I hope this is better, let me know if not.

That was excellent! Thanks a lot!
You sound like some one I could learn a lot from! I appreciate it!

So when this pocket is blocked and it prevents it from generating signals in the neurons, are we talking strictly about pain/nerve impulses? Or does this include neurotransmitter release? I find gabapentin greatly enhances opioid euphoria to a degree and is even euphoric in high enough doses on it's own.

I know that things like benzodiazepines reduce the neurotransmitter signals in the brain, which can actually block the euphoria of some drugs (this has been my experience and sounds like that's how it would work pharmacology speaking), but some may disagree with this and find benzos add to the euphoria of their opiates.

The tolerance part makes sense. I wonder if gabapentin does act on this g protein.
Are you aware of any other medicines that do and are easily accessible?

I am on buprenorphine and all of it's mood lifting and warm glow feelings have all but disappeared a long time ago and unfortunately while they were still present, it made buprenorphine an excellent antidepressant for me. But with my degree of tolerance to bupe now, it's almost worthless to take it.

Anyway, I appreciate it! Thank you!

 

[psynce of sound]

That was excellent! Thanks a lot!
You sound like some one I could learn a lot from! I appreciate it!

So when this pocket is blocked and it prevents it from generating signals in the neurons, are we talking strictly about pain/nerve impulses? Or does this include neurotransmitter release? I find gabapentin greatly enhances opioid euphoria to a degree and is even euphoric in high enough doses on it's own.

I know that things like benzodiazepines reduce the neurotransmitter signals in the brain, which can actually block the euphoria of some drugs (this has been my experience and sounds like that's how it would work pharmacology speaking), but some may disagree with this and find benzos add to the euphoria of their opiates.

The tolerance part makes sense. I wonder if gabapentin does act on this g protein.
Are you aware of any other medicines that do and are easily accessible?

I am on buprenorphine and all of it's mood lifting and warm glow feelings have all but disappeared a long time ago and unfortunately while they were still present, it made buprenorphine an excellent antidepressant for me. But with my degree of tolerance to bupe now, it's almost worthless to take it.

Anyway, I appreciate it! Thank you!

It doesn't effect the neurotransmitters themselves or their interactions with the given receptor. It alters the electric impulse that is generated by the neurotransmitters directly.

Ca+ channels are pretty much present wherever there are opportunities to generate a signal.

It must be said that with dampening some signals it can alter how corresponding neurotransmitter activity works.
For example if a drug works on serotonin and dopamine as a releaser, the dampening of one allows more of the other to do it's job.

Ketamine is one medicine that works on Mu receptors as well as the g protein. They both are found next to each other.
It both encourages the Receptors back out of the protein, it also forms a patch (or raft to use the terminology for the study) temporarily between the g protein and the receptor. Alongside it's ability to modulate Mu activity/sensitivity at the receptor without activating it.

I'd imagine thr bupe tolerance you experience will be effected by the things I have mentioned.
As a Mu antagonist it's still relative to how tolerance at Mu builds.

The main thing that goes on in Opioid tolerance reduction is the relationship between Mu and NMDA.

 

[Sharon228]

Antinociceptive effects of gabapentin & its mechanism of action in experimental animal studies

Several studies have shown the possible analgesic effects of gabapentin, widely used as an antiepileptic. Thus, clinical studies have been carried out especially for neuropathic syndroms. This study was undertaken to investigate experimentally whether ...

www.ncbi.nlm.nih.gov

Anyone care to pick this study apart?

It speaks about 2 different experiments and in one experiment, they found that naloxone reversed the analgesic relief of gabapentin, while the other experiment said it didn't.

"Gabapentin (30 mg/kg) combined with naloxone in our experimental study did not reveal any peripheral effect. However, Hansen et al19 observed that gabapentin at spinal level prevents opiod tolerance, and reveals a better spinal analgesic effect compared to single use6, and that the antinociceptive effect of gabapentin is reversed with naloxone16. These studies were conducted with neuropathic pain models."

It also mentions that gabapentin reverses morphine tolerance..

I initially looked up this information because I am prescribed gabapentin and suboxone. I noticed the other day after taking a dose of gabapentin and it being in full effect, I took some more suboxone and what happened next I can only describe as sudden precipitated withdrawal. Sweats, a return of pain (all through out my body), dysphoria, etc...

I have given myself precipitated withdrawal several times in the past from taking subs too soon after heroin. This felt exactly like that, but lasted only maybe about 20 minutes.

If naloxone could reverse gabapentin, wouldn't that imply some sort of opioid mechanism? And which study should be believed since the study in the link says naloxone had no effect on gabapentin.

I have also read that gabapentin has pretty much nothing to do with gaba or the gaba A & B receptors, yet this study says...
"It has been reported that gabapentin slightly increases the systolic and diastolic blood pressure on intra-cerebroventricüler administration5–7. Studies have primarily been conducted on its effects on GABAB receptors4."

So which is it, does gabapentin affect gaba B receptor or does it not?

Any one with a little more understanding about all this care to pick it apart?
Was the precipitated withdrawal I felt all in my head?
And I have noticed hallucinations from gabapentin withdrawal, which to me would indicate some kind of action at one of the gaba receptor sites (I would think).

Any one with any more input or knowledge (in layman's terms) of the mechanism of action of gabapentin?

 

[Sharon228]

New to BluelightAlso, appreciate any, and all answers, knowledge, the research https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3401692/ you all shared regarding the mechanism of action of gabapentin. Thank you to everyone! Great answers. I will be sure to do my own research too!

 

[Xorkoth]

New to BluelightAlso, appreciate any, and all answers, knowledge, the research https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3401692/ you all shared regarding the mechanism of action of gabapentin. Thank you to everyone! Great answers. I will be sure to do my own research too!

Welcome to Bluelight!

 

[The Holy Quadruplty]

Antinociceptive effects of gabapentin & its mechanism of action in experimental animal studies

Several studies have shown the possible analgesic effects of gabapentin, widely used as an antiepileptic. Thus, clinical studies have been carried out especially for neuropathic syndroms. This study was undertaken to investigate experimentally whether ...

www.ncbi.nlm.nih.gov

Anyone care to pick this study apart?

It speaks about 2 different experiments and in one experiment, they found that naloxone reversed the analgesic relief of gabapentin, while the other experiment said it didn't.

"Gabapentin (30 mg/kg) combined with naloxone in our experimental study did not reveal any peripheral effect. However, Hansen et al19 observed that gabapentin at spinal level prevents opiod tolerance, and reveals a better spinal analgesic effect compared to single use6, and that the antinociceptive effect of gabapentin is reversed with naloxone16. These studies were conducted with neuropathic pain models."

It also mentions that gabapentin reverses morphine tolerance..

I initially looked up this information because I am prescribed gabapentin and suboxone. I noticed the other day after taking a dose of gabapentin and it being in full effect, I took some more suboxone and what happened next I can only describe as sudden precipitated withdrawal. Sweats, a return of pain (all through out my body), dysphoria, etc...

I have given myself precipitated withdrawal several times in the past from taking subs too soon after heroin. This felt exactly like that, but lasted only maybe about 20 minutes.

If naloxone could reverse gabapentin, wouldn't that imply some sort of opioid mechanism? And which study should be believed since the study in the link says naloxone had no effect on gabapentin.

I have also read that gabapentin has pretty much nothing to do with gaba or the gaba A & B receptors, yet this study says...
"It has been reported that gabapentin slightly increases the systolic and diastolic blood pressure on intra-cerebroventricüler administration5–7. Studies have primarily been conducted on its effects on GABAB receptors4."

So which is it, does gabapentin affect gaba B receptor or does it not?

Any one with a little more understanding about all this care to pick it apart?
Was the precipitated withdrawal I felt all in my head?
And I have noticed hallucinations from gabapentin withdrawal, which to me would indicate some kind of action at one of the gaba receptor sites (I would think).

Any one with any more input or knowledge (in layman's terms) of the mechanism of action of gabapentin?

For gabapentin possibly having opioid effects, I wouldn't doubt that it binds to the ORL1 (opioid receptor like) being that it has an antinoceceptive effect, which I'm pretty sure those come from the Opioid Receptor Like 1.